This collection contains data from the Southwest Oncology Group (SWOG) Clinical Trial NCT00946712, “Carboplatin and Paclitaxel With or Without Bevacizumab and/or Cetuximab in Treating Patients With Stage IV or Recurrent Non-Small Cell Lung Cancer". Principal Investigator: Roy Herbst. It was sponsored by NCI and performed by the Southwest Oncology Group under study number S0819. This randomized phase III trial studies carboplatin and paclitaxel to compare how well they work with or without bevacizumab and/or cetuximab in treating patients with stage IV or non-small cell lung cancer that has returned after a period of improvement (recurrent). Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Bevacizumab may prevent the growth of new blood vessels that tumor needs to grow. Cetuximab may also stop cancer cells from growing by binding and interfering with a protein on the surface of the tumor cell that is needed for tumor growth. It is not yet known whether giving carboplatin and paclitaxel are more effective with or without bevacizumab and/or cetuximab in treating patients with non-small cell lung cancer. Select patient-level data from this trial is available via the following link: https://nctn-data-archive.nci.nih.gov/node/850.

Trial Outcomes

Results of the trial have been reported in the following publications:

• Hirsch FR, Redman MW, Moon J, Agustoni F, Herbst RS, Semrad TJ, Varella-Garcia M, Rivard CJ, Kelly K, Gandara DR, Mack PC. EGFR High Copy Number Together With High EGFR Protein Expression Predicts Improved Outcome for Cetuximab-based Therapy in Squamous Cell Lung Cancer: Analysis From SWOG S0819, a Phase III Trial of Chemotherapy With or Without Cetuximab in Advanced NSCLC. Clin Lung Cancer. 2022 Jan;23(1):60-71. doi: 10.1016/j.cllc.2021.10.002. Epub 2021 Oct 10.

• Herbst RS, Redman MW, Kim ES, Semrad TJ, Bazhenova L, Masters G, Oettel K, Guaglianone P, Reynolds C, Karnad A, Arnold SM, Varella-Garcia M, Moon J, Mack PC, Blanke CD, Hirsch FR, Kelly K, Gandara DR. Cetuximab plus carboplatin and paclitaxel with or without bevacizumab versus carboplatin and paclitaxel with or without bevacizumab in advanced NSCLC (SWOG S0819): a randomised, phase 3 study. Lancet Oncol. 2018 Jan;19(1):101-114. doi: 10.1016/S1470-2045(17)30694-0. Epub 2017 Nov 20.

This collection contains data from the Southwest Oncology Group (SWOG) Clinical Trial NCT00946712, “Carboplatin and Paclitaxel With or Without Bevacizumab and/or Cetuximab in Treating Patients With Stage IV or Recurrent Non-Small Cell Lung Cancer". Principal Investigator: Roy Herbst. It was sponsored by NCI and performed by the Southwest Oncology Group under study number S0819. This randomized phase III trial studies carboplatin and paclitaxel to compare how well they work with or without bevacizumab and/or cetuximab in treating patients with stage IV or non-small cell lung cancer that has returned after a period of improvement (recurrent). Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Bevacizumab may prevent the growth of new blood vessels that tumor needs to grow. Cetuximab may also stop cancer cells from growing by binding and interfering with a protein on the surface of the tumor cell that is needed for tumor growth. It is not yet known whether giving carboplatin and paclitaxel are more effective with or without bevacizumab and/or cetuximab in treating patients with non-small cell lung cancer. Select patient-level data from this trial is available via the following link: https://nctn-data-archive.nci.nih.gov/node/850.

Trial Outcomes

Results of the trial have been reported in the following publications:

• Hirsch FR, Redman MW, Moon J, Agustoni F, Herbst RS, Semrad TJ, Varella-Garcia M, Rivard CJ, Kelly K, Gandara DR, Mack PC. EGFR High Copy Number Together With High EGFR Protein Expression Predicts Improved Outcome for Cetuximab-based Therapy in Squamous Cell Lung Cancer: Analysis From SWOG S0819, a Phase III Trial of Chemotherapy With or Without Cetuximab in Advanced NSCLC. Clin Lung Cancer. 2022 Jan;23(1):60-71. doi: 10.1016/j.cllc.2021.10.002. Epub 2021 Oct 10.

• Herbst RS, Redman MW, Kim ES, Semrad TJ, Bazhenova L, Masters G, Oettel K, Guaglianone P, Reynolds C, Karnad A, Arnold SM, Varella-Garcia M, Moon J, Mack PC, Blanke CD, Hirsch FR, Kelly K, Gandara DR. Cetuximab plus carboplatin and paclitaxel with or without bevacizumab versus carboplatin and paclitaxel with or without bevacizumab in advanced NSCLC (SWOG S0819): a randomised, phase 3 study. Lancet Oncol. 2018 Jan;19(1):101-114. doi: 10.1016/S1470-2045(17)30694-0. Epub 2017 Nov 20.

Summary

This metadata record provides details of the data supporting the claims of the related article: “Effect of Metformin versus Placebo on Metabolic Factors in the MA.32 Randomized Adjuvant Breast Cancer Trial”.

The related study examined metformin impact on metabolic factors in non-diabetic subjects to determine whether this impact varies by baseline BMI, insulin and rs11212617 SNP in CCTG MA.32, a double-blind placebo controlled randomised adjuvant breast cancer (BC) trial.

Type of data: single-nucleotide polymorphism (SNP); clinical data

Subject of data: Homo sapiens

Sample size: 2915

Population characteristics: See Table 1 of the related article

Trial registration number: http://clinicaltrials.gov/show/NCT01101438

Data access

The SNP data are openly available as part of this figshare metadata record in the file ‘MA32_snp_data.csv’.

The primary efficacy analysis will be available from the Canadian Cancer Trials Group (Kingston, Ontario) after the results of the analysis have been published. These data will be uploaded to the NCI data archive website: https://nctn-data-archive.nci.nih.gov/view-trials and will be searchable via NCT trial number NCT01101438. As of April 2021, the group is working towards this publication. Further details can be requested from the corresponding author.

The clinical data are not publicly available for the following reason: data contain information that could compromise research participant privacy.

Corresponding author(s) for this study

Dr. Pamela J. Goodwin, Mount Sinai Hospital, 1085-600 University Avenue, Toronto, Ontario M5G 1X4. Tel: 416-586-8211. Fax: 416-586-3199. Email: Pamela.Goodwin@sinaihealthsystem.ca.

Study approval

The study protocol was approved by institutional review boards of participating institutions, including the NCI (US) Central Institutional Review Board and Mount Sinai Hospital (Ontario Cancer Research Ethics Board).

This dataset relates to NCI Clinical trial, "Magnetic Resonance Imaging in Women Recently Diagnosed With Unilateral Breast Cancer (ACRIN-6667)". The dataset consists of 984 patients but only 969 were included in the primary data analysis due to study criteria.

Even after careful clinical and mammographic evaluation, cancer is found in the contralateral breast in up to 10% of women who have received treatment for unilateral breast cancer. ACRIN 6667 was conducted to determine whether magnetic resonance imaging (MRI) could improve on clinical breast examination and mammography in detecting contralateral breast cancer soon after the initial diagnosis of unilateral breast cancer. Additional information about the trial is available in the Study Protocol and Case Report Forms.

METHODS

A total of 969 women with a recent diagnosis of unilateral breast cancer and no abnormalities on mammographic and clinical examination of the contralateral breast underwent breast MRI. The diagnosis of MRI-detected cancer was confirmed by means of biopsy within 12 months after study entry. The absence of breast cancer was determined by means of biopsy, the absence of positive findings on repeat imaging and clinical examination, or both at 1 year of follow-up.

RESULTS

MRI detected clinically and mammographically occult breast cancer in the contralateral breast in 30 of 969 women who were enrolled in the study (3.1%). The sensitivity of MRI in the contralateral breast was 91%, and the specificity was 88%. The negative predictive value of MRI was 99%. A biopsy was performed on the basis of a positive MRI finding in 121 of the 969 women (12.5%), 30 of whom had specimens that were positive for cancer (24.8%); 18 of the 30 specimens were positive for invasive cancer. The mean diameter of the invasive tumors detected was 10.9 mm. The additional number of cancers detected was not influenced by breast density, menopausal status, or the histologic features of the primary tumor.

CONCLUSIONS

MRI can detect cancer in the contralateral breast that is missed by mammography and clinical examination at the time of the initial breast-cancer diagnosis.

This dataset contains image annotations derived from the NCI Clinical Trial "A Randomized Phase III Study Comparing Carboplatin/Paclitaxel or Carboplatin/Paclitaxel/Bevacizumab With or Without Concurrent Cetuximab in Patients With Advanced Non-small Cell Lung Cancer”. This dataset was generated as part of an NCI project to augment TCIA datasets with annotations that will improve their value for cancer researchers and AI developers.

Annotation Protocol

For each patient, all scans were reviewed to identify and annotate the clinically relevant time points and sequences/series. Scans were initially annotated by an international team of radiologists holding MBBS degrees or higher, which were then reviewed by US-based board-certified radiologists to ensure accuracy. In a typical patient, all available time points were annotated. Every exam from the first available time point was annotated. One additional time point was annotated for each patient. The clinical data in the NCTN Archive was utilized to help determine the first evidence of disease progression. The first time point demonstrating disease progression was annotated. If that document was not accurate and did not demonstrate disease progression, then later time points were reviewed to assess for disease progression and the first time point demonstrating disease progression was annotated. If there was no evidence of disease progression on any time point, then the last available time point was annotated. Again, every exam from each chosen time point was annotated. For example, if there was a CT and a PET/CT, the PET was annotated along with one CT. If there was an MRI, that was annotated as well. The following annotation rules were followed:

1. PERCIST criteria was followed for PET imaging. Specifically, the lesions estimated to have the most elevated SUVmax were annotated.
2. RECIST 1.1 was otherwise generally followed for any MR and CT imaging. A maximum of 5 lesions were annotated per patient scan (timepoint); no more than 2 per organ. The same 5 lesions were annotated at each time point. Lymph nodes were however annotated if > 1 cm in short axis. Other lesions were annotated if > 1 cm. If the primary lesion is < 1 cm, it was still annotated. If there was evidence of disease progression with new lesions then additional annotations were allowed to demonstrate that progression. A representative sample of the new lesions was annotated at the radiologist's discretion.
3. Lesions were annotated in the axial plane. If no axial plane was available, lesions were annotated in the coronal plane.
4. MRIs were annotated using the T1-weighted post contrast sequence, fat saturated if available. If not available, T2-weighted sequences were utilized.
5. CTs were annotated using the axial post contrast series. If not available, the non contrast series was annotated.
6. PET/CTs were annotated on the CT and attenuation corrected PET images. However, if the post contrast CT was performed the same day as the PET/CT, the non contrast CT portion of the PET/CT was annotated.
7. Lesions were labeled separately.
8. The volume of each annotated lesion was calculated and reported in cubic centimeters [cc] in a dataset metadata report.
9. Seed points were automatically generated but reviewed by a radiologist.
10. A “negative” annotation was created for any exam without findings.

At each time point:

1. A seed point (kernel) was created for each segmented structure. The seed points for each segmentation are provided in a separate DICOM RTSS file.
2. SNOMED-CT “Anatomic Region Sequence” and “Segmented Property Category Code Sequence” and codes were inserted for all segmented structures.
3. “Tracking ID” and “Tracking UID” tags were inserted for each segmented structure to enable longitudinal lesion tracking.
4. Imaging time point codes were inserted to help identify each annotation in the context of the clinical trial assessment protocol.
   1. “Clinical Trial Time Point ID” was used to encode time point type using one of the following strings as applicable: “pre-dose” or “post-chemotherapy”
   2. Content Item in “Acquisition Context Sequence” was added containing "Time Point Type" using Concept Code Sequence (0040,A168) selected from:
      1. (255235001, SCT, “Pre-dose”)
      2. (262502001, SCT, "Post-chemotherapy")

Important supplementary information and sample code

1. A spreadsheet containing key details about the annotations is available in the Data Access section below.
2. A Jupyter notebook demonstrating how to use the NBIA Data Retriever Command-Line Interface application and the REST API to access these data can be found in the Additional Resources section below.

This collection contains data from the Children’s Oncology Group (COG) Clinical Trial NCT00392327, "Chemotherapy and Radiation Therapy in Treating Young Patients With Newly Diagnosed, Previously Untreated, High-Risk Medulloblastoma/PNET". The Study Chair was James M. Olson, M.D., Ph.D. It was sponsored by NCI and performed by the Children's Oncology Group under study number ACNS0332. This randomized phase III trial studies different chemotherapy and radiation therapy regimens to compare how well they work in treating young patients with newly diagnosed, previously untreated, high-risk medulloblastoma. Select patient-level clinical data from this trial is available via the following link: https://nctn-data-archive.nci.nih.gov/node/838.

Trial Description

Children with histologically diagnosed high-risk medulloblastoma, supratentorial primitive neuro-ectodermal tumor of the CNS (CNS-PNET), and pineoblastoma (PBL) have had poor survival despite intensive treatment. The Children’s Oncology Group (COG) study ACNS0332 was designed to test two approaches for treatment intensification for these patients: addition of carboplatin during irradiation and/or addition of isotretinoin to the adjuvant regimen. Carboplatin has demonstrated preclinical and clinical efficacy in these tumors and is well tolerated in children, whereas isotretinoin crosses the blood-brain barrier efficiently and is effective against preclinical models of medulloblastoma (MB). Molecular profiling later revealed tumor heterogeneity that was not detectable at protocol inception. Enrollment of patients with CNS-PNET/PBL was subsequently discontinued, and outcomes for this part of the study reported. Eighty-five participants with institutionally diagnosed CNS-PNETs/PBLs were enrolled. Of 60 patients with sufficient tissue, 31 had tumors that were non-pineal in location. Twenty-two patients (71%) of those 31 were diagnosed with tumor types not intended for trial inclusion, including 18 high-grade (HGGs), two atypical teratoid rhbdoid tumors, and 2 ependymomas. Outcomes across tumor types were strikingly different. Neither carboplatin, nor isotretinoin significantly altered outcomes for all patients. Survival for patients with HGG was similar to that of historic studies that avoid craniospinal irradiation and intensive chemotherapy. For patients with CNS-PNET/PBL, prognosis is considerably better than previously assumed when molecularly confirmed HGGs are removed. Identification of molecular HGGs may spare affected children from unhelpful intensive treatment. This trial highlights the challenges of a histology-based diagnosis for pediatric brain tumors and indicates that molecular profiling should become a standard component of initial diagnosis.

Pre-operative and post-operative MRI scans of the brain with and without contrast and spinal MRI with and without contrast were required. All scans underwent central review.

Trial Outcomes

Results of the trial have been reported in the following publication:

Hwang, E. I., Kool, M., Burger, P. C., Capper, D., Chavez, L., Brabetz, S., Williams-Hughes, C., Billups, C., Heier, L., Jaju, A., Michalski, J., Li, Y., Leary, S., Zhou, T., von Deimling, A., Jones, D. T. W., Fouladi, M., Pollack, I. F., Gajjar, A., … Olson, J. M. (2018). Extensive Molecular and Clinical Heterogeneity in Patients With Histologically Diagnosed CNS-PNET Treated as a Single Entity: A Report From the Children’s Oncology Group Randomized ACNS0332 Trial. Journal of Clinical Oncology, 36(34), 3388–3395. https://doi.org/10.1200/jco.2017.76.4720. Epub ahead of print. PMID: 30332335.

This collection contains data from the Alliance for Clinical Trials in Oncology Clinical Trial NCT02066181 “Sorafenib Tosylate in Treating Patients With Desmoid Tumors or Aggressive Fibromatosis". Principal Investigator: Mrinal M Gounder. It was sponsored by NCI and performed by the Alliance for Clinical Trials in Oncology under study number A091105. This randomized phase III trial compares the effects, good and/or bad, of sorafenib tosylate in treating patients with desmoid tumors or aggressive fibromatosis. Sorafenib tosylate may stop the growth of tumor cells by blocking some of the proteins needed for cell growth. Select patient-level data from this trial is available via the following link: https://nctn-data-archive.nci.nih.gov/node/1266.

Trial Outcomes

Results of the trial have been reported in the following publications:

• Mazza GL, Petersen MM, Ginos B, Langlais BT, Heon N, Gounder MM, Mahoney MR, Zoroufy AJ, Schwartz GK, Rogak LJ, Thanarajasingam G, Basch E, Dueck AC. Missing data strategies for the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) in Alliance A091105 and COMET-2. Qual Life Res. 2022 Apr;31(4):1069-1080. doi: 10.1007/s11136-021-02968-1. Epub 2021 Aug 21. Erratum in: Qual Life Res. 2021 Oct 11.
• Basch E, Becker C, Rogak LJ, Schrag D, Reeve BB, Spears P, Smith ML, Gounder MM, Mahoney MR, Schwartz GK, Bennett AV, Mendoza TR, Cleeland CS, Sloan JA, Bruner DW, Schwab G, Atkinson TM, Thanarajasingam G, Bertagnolli MM, Dueck AC. Composite grading algorithm for the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). Clin Trials. 2021 Feb;18(1):104-114. doi: 10.1177/1740774520975120. Epub 2020 Dec 1.
• Gounder MM, Mahoney MR, Van Tine BA, Ravi V, Attia S, Deshpande HA, Gupta AA, Milhem MM, Conry RM, Movva S, Pishvaian MJ, Riedel RF, Sabagh T, Tap WD, Horvat N, Basch E, Schwartz LH, Maki RG, Agaram NP, Lefkowitz RA, Mazaheri Y, Yamashita R, Wright JJ, Dueck AC, Schwartz GK. Sorafenib for Advanced and Refractory Desmoid Tumors. N Engl J Med. 2018 Dec 20;379(25):2417-2428. doi: 10.1056/NEJMoa1805052.

This collection contains data from the Children’s Oncology Group (COG) Clinical Trial NCT00274937, “Radiation Therapy, Amifostine, and Chemotherapy in Treating Young Patients With Newly Diagnosed Nasopharyngeal Cancer". Principal Investigator: Carlos Rodriguez-Galindo, MD. It was sponsored by NCI and performed by the Children's Oncology Group under study number ARAR0331. This phase III trial is studying how well radiation therapy, amifostine, and chemotherapy work in treating young patients with newly diagnosed nasopharyngeal cancer. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs, such as amifostine, may protect normal cells from the side effects of radiation therapy. Drugs used in chemotherapy, such as cisplatin and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving radiation therapy together with amifostine and chemotherapy may kill more tumor cells. Select patient-level data from this trial is available via the following link: https://nctn-data-archive.nci.nih.gov/node/1302.

Trial Outcomes

Results of the trial have been reported in the following publications:

• Jeha S, Pei D, Choi J, Cheng C, Sandlund JT, Coustan-Smith E, Campana D, Inaba H, Rubnitz JE, Ribeiro RC, Gruber TA, Raimondi SC, Khan RB, Yang JJ, Mullighan CG, Downing JR, Evans WE, Relling MV, Pui CH. Improved CNS Control of Childhood Acute Lymphoblastic Leukemia Without Cranial Irradiation: St Jude Total Therapy Study 16. J Clin Oncol. 2019 Dec 10;37(35):3377-3391. doi: 10.1200/JCO.19.01692. Epub 2019 Oct 28.
• Rodriguez-Galindo C, Krailo MD, Krasin MJ, Huang L, McCarville MB, Hicks J, Pashankar F, Pappo AS. Treatment of Childhood Nasopharyngeal Carcinoma With Induction Chemotherapy and Concurrent Chemoradiotherapy: Results of the Children's Oncology Group ARAR0331 Study. J Clin Oncol. 2019 Dec 10;37(35):3369-3376. doi: 10.1200/JCO.19.01276. Epub 2019 Sep 25. Erratum in: J Clin Oncol. 2021 May 10;39(14):1602.

This collection contains data from the Children’s Oncology Group (COG) Clinical Trial NCT01026220, “Combination Chemotherapy and Radiation Therapy in Treating Young Patients With Newly Diagnosed Hodgkin Lymphoma". Principal Investigator: Kara Kelly, MD (pediatric oncologist and the Chair of Roswell Park Oishei Children’s Cancer and Blood Disorders Program, Buffalo, NY). It was sponsored by NCI and performed by the Children's Oncology Group under study number AHOD0831. This phase III trial is studying how well giving combination chemotherapy together with radiation therapy works in treating young patients with newly diagnosed Hodgkin lymphoma. Therapeutic agents used on trial include 1 or more of the following: Biological: bleomycin sulfate; Drug: doxorubicin hydrochloride; Drug: liposomal vincristine sulfate; Drug: vinorelbine tartrate; Drug: cyclophosphamide; Drug: etoposide phosphate; Drug: prednisone; Biological: filgrastimDrug: ifosfamide. Select patient-level clinical data from this trial is available via the following link: https://nctn-data-archive.nci.nih.gov/node/1137.

Trial Primary Objective:

I. To maintain the overall survival (as defined by 4-year "second-event" free survival) for subjects with high risk Hodgkin lymphoma at or above 95%.

Trial Secondary Objectives:

I. To maintain 3-year event-free survival for subjects with high risk Hodgkin lymphoma at or above 93%.

II. To maintain comparable overall survival (as defined by 4-year "second-event" free survival) between subjects with high risk Hodgkin lymphoma who have a rapid or slow response to the initial 2 cycles of ABVE-PC* by intensifying therapy through the addition of 2 cycles of ifosfamide/vinorelbine in those with a slow early response.

III. To investigate whether very early response assessment measured by FDG-PET after 1 cycle of chemotherapy identifies a subject cohort that can be studied in future trials and that is distinguishable from currently defined RER after 2 cycles.

IV. To describe the patterns of relapse after ABVE-PC* and risk-adapted radiotherapy.

Trial Description and Outcomes

The AHOD0831 study for pediatric patients with high risk Hodgkin lymphoma tested a response-based approach designed to limit cumulative alkylator exposure and reduce radiation volumes. 166 patients were enrolled in this study from December 2009 to January 2012, of whom 165 were eligible and 141 completed the trial. This dataset contains the images from the 165 eligible patients. Study dates were approximately 2009-2017.

Patients (Stage IIIB/IVB) received two cycles of ABVE-PC (doxorubicin, bleomycin, vincristine, etoposide, prednisone, cyclophosphamide). Rapid early responders [RER, no positron emission tomography (PET) activity above mediastinal blood pool] were consolidated with 2 cycles of ABVE-PC. Slow early responders(SER) received 2 cycles of ifosfamide/vinorelbine and 2 cycles of ABVE-PC.

Radiotherapy was administered to sites of initial bulk and/or SER. By intent-to-treat analysis, 4-year second event-free survival (EFS; freedom from second relapse or malignancy) was 91.9% [95% confidence interval(CI): 86.1 – 95.3%], below the projected baseline of 95% (P = 0.038). Five-year first EFS and overall survival (OS) rates are 79.1% (95% CI: 71.5 –84.8%) and 95% (95% CI: 88.8 – 97.8%). Eight of 11 SER patients with persistent PET positive lesions at the end of chemotherapy had clinical evidence of active disease (3 biopsy-proven, 5 with progressive disease or later relapses). Although this response-directed approach did not reach the ambitiously high pre-specified target for second EFS, EFS and OS rates are comparable with results of recent trials despite the reduction in radiotherapy volumes from historical involved fields. Persistent PET at end of chemotherapy identifies a cohort at an especially high risk for relapse/early progression.

Trial Publication

Results of the trial have been reported in the following publication:

• Kelly KM, Cole PD, Pei Q, Bush R, Roberts KB, Hodgson DC, McCarten KM, Cho SY, Schwartz C. Response-adapted therapy for the treatment of children with newly diagnosed high risk Hodgkin lymphoma (AHOD0831): a report from the Children's Oncology Group. Br J Haematol. 2019 Oct;187(1):39-48. doi: 10.1111/bjh.16014. Epub 2019 Jun 10. PMID: 31180135; PMCID: PMC6857800.

This collection contains data from the Children’s Oncology Group (COG) Clinical Trial NCT00379340, “Combination Chemotherapy With or Without Radiation Therapy in Treating Young Patients With Newly Diagnosed Stage III or Stage IV Wilms Tumor, " Study Chair: David Dix, MD. It was sponsored by NCI and performed by the Children's Oncology Group under study number AREN0533. This phase III trial is studying how well combination chemotherapy with or without radiation therapy works in treating young patients with newly diagnosed stage III or stage IV favorable histology Wilms tumor. Select patient-level clinical data from this trial is available via the following link: https://nctn-data-archive.nci.nih.gov/node/737.

Trial Description

Patients with stage IV favorable histology Wilms tumor (FHWT), the majority of whom have pulmonary metastases, have inferior outcomes compared with those with localized disease. Their treatment is also complicated by a risk of late effects, including cardiac dysfunction, lung toxicity, musculoskeletal and soft tissue defects, and second malignancies. The AREN0533 study applied two separate strategies for risk stratification for patients with Stage III and IV favorable histology Wilms tumor. The first is the identification of patients with pulmonary nodules who can be spared bilateral pulmonary irradiation. Patients with Stage IV favorable histology Wilms tumor have a 4-year event-free survival (EFS) of 75% with chemotherapy and irradiation to sites of metastatic disease (most frequently in the lungs). European investigators are able to spare 75% of their patients with pulmonary nodules from irradiation based on the initial response to chemotherapy. The response of the lung metastases to 6 weeks of chemotherapy consisting of vincristine, dactinomycin, and doxorubicin (Regimen DD-4A) was used to determine if radiation of lung nodules is needed. Patients who had complete disappearance of their lung metastases (or who had tissue confirmation that the nodules do not contain viable tumor) at the Week 6 evaluation were considered rapid responders and continued with DD-4A. Patients who did not have complete resolution of pulmonary nodules by Chest CT underwent pulmonary irradiation and were switched to Regimen M (DD-4A variation with dactinomycin and doxorubicin given on the same day plus cyclophosphamide and etoposide). Central radiology review of the chest CTs were performed on all Stage IV patients with lung metastases at study enrollment and at Week 6. The second risk stratification variable was the allelic loss of 1p and 16q. Patients with Stage III and IV favorable histology Wilms tumor with loss of heterozygosity (LOH) of both 1p and 16q have a 4-yr EFS of 65%. Patients with LOH of 1p and 16q were assigned to Regimen M in an attempt to improve the 4-year EFS of this group of patients to 84%.

Trial Outcomes

Results of the trial have been reported in the following publications:

• Dix DB, Seibel NL, Chi YY, Khanna G, Gratias E, Anderson JR, Mullen EA, Geller JI, Kalapurakal JA, Paulino AC, Perlman EJ, Ehrlich PF, Malogolowkin M, Gastier-Foster JM, Wagner E, Grundy PE, Fernandez CV, Dome JS. Treatment of Stage IV Favorable Histology Wilms Tumor With Lung Metastases: A Report From the Children's Oncology Group AREN0533 Study. J Clin Oncol. 2018 Jun 1;36(16):1564-1570. doi: 10.1200/JCO.2017.77.1931. Epub 2018 Apr 16. PMID: 29659330; PMCID: PMC6075846.
• Dix, D. B., Fernandez, C. V., Chi, Y.-Y., Mullen, E. A., Geller, J. I., Gratias, E. J., Khanna, G., Kalapurakal, J. A., Perlman, E. J., Seibel, N. L., Ehrlich, P. F., Malogolowkin, M., Anderson, J., Gastier-Foster, J., Shamberger, R. C., Kim, Y., Grundy, P. E., & Dome, J. S. (2019). Augmentation of Therapy for Combined Loss of Heterozygosity 1p and 16q in Favorable Histology Wilms Tumor: A Children’s Oncology Group AREN0532 and AREN0533 Study Report. In Journal of Clinical Oncology (Vol. 37, Issue 30, pp. 2769–2777). American Society of Clinical Oncology (ASCO). https://doi.org/10.1200/jco.18.01972

This collection contains data from the Children’s Oncology Group (COG) Clinical Trial NCT00352534, “Vincristine, Dactinomycin, and Doxorubicin With or Without Radiation Therapy or Observation Only in Treating Younger Patients Who Are Undergoing Surgery for Newly Diagnosed Stage I, Stage II, or Stage III Wilms' Tumor". Principal Investigator: Conrad Fernandez, MD in Halifax, NS. It was sponsored by NCI and performed by the Children's Oncology Group under study number AREN0532. This phase III trial is studying vincristine, dactinomycin, and doxorubicin with or without radiation therapy or observation only to see how well they work in treating patients undergoing surgery for newly diagnosed stage I, stage II, or stage III Wilms' tumor. Select patient-level clinical data from this trial is available via the following link: https://nctn-data-archive.nci.nih.gov/node/689.

Trial Description

COG AREN0532 is a treatment study of kidney tumors which have not spread to other parts of the body. 544 very low and standard risk favorable histology Wilms Tumor patients entered the trial. At accrual all patients were Stage I-III and had not received any prior therapy. Dates of therapy were from 2006 to 2013.

The National Wilms Tumor Study (NWTS) approach to treating stage III favorable-histology Wilms tumor (FHWT) is Regimen DD4A (vincristine, dactinomycin, and doxorubicin) and radiation therapy. Further risk stratification is desired to improve outcomes and reduce late effects. In a 2018 JCO paper, the trial evaluated clinical and biologic variables for patients with stage III FHWT without combined loss of heterozygosity (LOH) at chromosomes 1p and 16q. This paper included 535 patients with stage III disease. Relapse after stage III treatment is associated with an overall survival (OS) of only 50% despite intensive salvage chemotherapy and/or autologous bone marrow transplantation. It is thus highly desirable to identify patients who need augmentation of initial therapy with the hope of preventing relapse.

A novel finding in this study was the remarkably strong predictive value of combining LOH and lymph node status. The relapse rate was exceptionally low among patients with tumors that were LOH - and lymph node – negative. However, this trial demonstrated that those with combined lymph node involvement and LOH 1p or 16q had a significantly worse 4-year EFS outcome of 74%. There is a trend toward a poorer 4-year OS in this comparison; however, it is not statistically different.

Approximately two thirds of patients had delayed-nephrectomy tissue submitted for central pathology review. Most patients with blastemal-type Wilms tumor but none of seven patients with low-risk/ completely necrotic Wilms tumor experienced relapse, consistent with the findings of the International Society of Pediatric Oncology (SIOP) that histologic response to preoperative chemotherapy plays an important role in predicting outcome.

The results of this trial described the overall good outcome of patients with stage III FHWT using DD4A with radiation therapy and identified an association of combined lymph node and LOH status, as well as postchemotherapy, delayed nephrectomy histology, with EFS.

Data from the 2018 J Clin Oncol. paper, cited below: A total of 535 patients with stage III disease were studied. Median follow-up was 5.2 years (range, 0.2 to 9.5). Four-year event-free survival (EFS) and overall survival estimates were 88% (95% CI,85% to 91%) and 97% (95% CI, 95% to 99%), respectively. A total of 58 of 66 relapses occurred in the first 2 years, predominantly pulmonary (n = 36). Eighteen patients died, 14 secondary to disease.

A better EFS was associated with negative lymph node status (P less than .01) and absence of LOH 1p or 16q (P less than .01), but not with gross residual disease or peritoneal implants. In contrast, the 4-year EFS was only 74% in patients with combined positive lymph node status and LOH 1p or 16q. A total of 123 patients (23%) had delayed nephrectomy. Submitted delayed nephrectomy histology showed anaplasia (n = 8; excluded from survival analysis); low risk/completely necrotic (n = 7; zero relapses), intermediate risk (n = 63; six relapses), and high-risk/blastemal type (n=7; five relapses).

Trial Outcomes

Results of the trial have been reported in the following publications:

• Fernandez CV, Mullen EA, Chi YY, Ehrlich PF, Perlman EJ, Kalapurakal JA, Khanna G, Paulino AC, Hamilton TE, Gow KW, Tochner Z, Hoffer FA, Withycombe JS, Shamberger RC, Kim Y, Geller JI, Anderson JR, Grundy PE, Dome JS. Outcome and Prognostic Factors in Stage III Favorable-Histology Wilms Tumor: A Report From the Children's Oncology Group Study AREN0532. J Clin Oncol. 2018 Jan 20;36(3):254-261. doi: 10.1200/JCO.2017.73.7999. Epub 2017 Dec 6. Erratum in: J Clin Oncol. 2019 Oct 10;37(29):2710. PMID: 29211618; PMCID: PMC5773840. https://doi.org/10.1200/jco.2017.73.7999
• Dix DB, Fernandez CV, Chi YY, Mullen EA, Geller JI, Gratias EJ, Khanna G, Kalapurakal JA, Perlman EJ, Seibel NL, Ehrlich PF, Malogolowkin M, Anderson J, Gastier-Foster J, Shamberger RC, Kim Y, Grundy PE, Dome JS; AREN0532 and AREN0533 study committees. Augmentation of Therapy for Combined Loss of Heterozygosity 1p and 16q in Favorable Histology Wilms Tumor: A Children's Oncology Group AREN0532 and AREN0533 Study Report. J Clin Oncol. 2019 Oct 20;37(30):2769-2777. doi: 10.1200/JCO.18.01972. Epub 2019 Aug 26. PMID: 31449468; PMCID: PMC7001789. https://doi.org/10.1200/jco.18.01972

Background: The aggressive and heterogeneous nature of lung cancer has thwarted efforts to reduce mortality from this cancer through the use of screening. The advent of low-dose helical computed tomography (CT) altered the landscape of lung-cancer screening, with studies indicating that low-dose CT detects many tumors at early stages. The National Lung Screening Trial (NLST) was conducted to determine whether screening with low-dose CT could reduce mortality from lung cancer.

Methods: From August 2002 through April 2004, we enrolled 53,454 persons at high risk for lung cancer at 33 U.S. medical centers. Participants were randomly assigned to undergo three annual screenings with either low-dose CT (26,722 participants) or single-view posteroanterior chest radiography (26,732). Data were collected on cases of lung cancer and deaths from lung cancer that occurred through December 31, 2009. This dataset includes the low-dose CT scans from 26,254 of these subjects, as well as digitized histopathology images from 451 subjects.

Results: The rate of adherence to screening was more than 90%. The rate of positive screening tests was 24.2% with low-dose CT and 6.9% with radiography over all three rounds. A total of 96.4% of the positive screening results in the low-dose CT group and 94.5% in the radiography group were false positive results. The incidence of lung cancer was 645 cases per 100,000 person-years (1060 cancers) in the low-dose CT group, as compared with 572 cases per 100,000 person-years (941 cancers) in the radiography group (rate ratio, 1.13; 95% confidence interval [CI], 1.03 to 1.23). There were 247 deaths from lung cancer per 100,000 person-years in the low-dose CT group and 309 deaths per 100,000 person-years in the radiography group, representing a relative reduction in mortality from lung cancer with low-dose CT screening of 20.0% (95% CI, 6.8 to 26.7; P=0.004). The rate of death from any cause was reduced in the low-dose CT group, as compared with the radiography group, by 6.7% (95% CI, 1.2 to 13.6; P=0.02).

Conclusions: Screening with the use of low-dose CT reduces mortality from lung cancer. (Funded by the National Cancer Institute; National Lung Screening Trial ClinicalTrials.gov number, NCT00047385).

Data Availability: A summary of the National Lung Screening Trial and its available datasets are provided on the Cancer Data Access System (CDAS). CDAS is maintained by Information Management System (IMS), contracted by the National Cancer Institute (NCI) as keepers and statistical analyzers of the NLST trial data. The full clinical data set from NLST is available through CDAS. Users of TCIA can download without restriction a publicly distributable subset of that clinical data, along with the CT and Histopathology images collected during the trial. (These previously were restricted.)

This collection contains data from the Children’s Oncology Group (COG) Clinical Trial NCT00945009, “Combination Chemotherapy and Surgery in Treating Young Patients With Wilms Tumor, " Study Chair: Peter F. Ehrlich, M.D. M.S.C. It was sponsored by NCI and performed by the Children's Oncology Group under study number AREN0534. This phase III trial studies how well combination chemotherapy and surgery work in treating young patients with Wilms tumor. Select patient-level clinical data from this trial is available via the following link: https://nctn-data-archive.nci.nih.gov/node/728.

Trial Description

Children with bilateral Wilms tumor account for 5-7% of all patients with Wilms tumor. Certain patients, with syndromes associated with Wilms tumor development, have been identified to be at increased risk for bilateral tumors. Due to an increased risk for renal failure, patients with bilateral disease at presentation are treated with preoperative chemotherapy in order to preserve renal parenchyma. Although this recommendation was made nearly 30 years ago, patients with bilateral tumors have not been formally studied in prior cooperative trials. Recent evidence suggests that survival of these patients is inferior to similar patients with unilateral tumor. This study is designed to improve the survival of these children, while continuing the emphasis on preserving renal function. Patients were enrolled and imaging studies were centrally reviewed to assess for bilateral renal lesions. They were treated with 3-drug induction chemotherapy (vincristine, dactinomycin, and doxorubicin) for 6 or 12 weeks based on radiographic response followed by surgery and further chemotherapy determined by histology. Radiation therapy was provided for postchemotherapy stage III and IV disease. One hundred eighty-nine of 208 patients were evaluable. Four-year EFS and OS were 82.1% (95% CI: 73.5%–90.8%) and 94.9% (95% CI: 90.1%–99.7%. Twenty-three patients relapsed and 7 had disease progression. After induction chemotherapy 163 of 189 (84.0%) underwent definitive surgical treatment in at least 1 kidney by 12 weeks and 39% retained parts of both kidneys. Surgical approaches included: unilateral total nephrectomy with contralateral partial nephrectomy (48%), bilateral partial nephrectomy (35%), unilateral total nephrectomy (10.5%), unilateral partial nephrectomy (4%), and bilateral total nephrectomies (2.5%). This treatment approach including standardized 3-drug preoperative chemotherapy, surgical resection within 12 weeks of diagnosis and response and histology-based postoperative therapy improved EFS and OS and preservation of renal parenchyma compared with historical outcomes for children with bilateral Wilms tumor.

Before enrollment, real-time central review of diagnostic imaging, pathology (if obtained), and operative notes confirmed the status of BWT. After 6 weeks, cross-sectional imaging was performed and a tumor response was assigned for each kidney. After 4 chemotherapy cycles (12 weeks), repeat cross sectional imaging was performed and definitive surgery was required. Response was based on the Response Evaluation Criteria in Solid Tumor (RECIST 1.1) modified to include 3 lesions per kidney.

Trial Outcomes

Results of the trial have been reported in the following publication:

• Ehrlich P, Chi YY, Chintagumpala MM, Hoffer FA, Perlman EJ, Kalapurakal JA, Warwick A, Shamberger RC, Khanna G, Hamilton TE, Gow KW, Paulino AC, Gratias EJ, Mullen EA, Geller JI, Grundy PE, Fernandez CV, Ritchey ML, Dome JS. Results of the First Prospective Multi-institutional Treatment Study in Children With Bilateral Wilms Tumor (AREN0534): A Report From the Children's Oncology Group. Ann Surg. 2017 Sep;266(3):470-478. doi: 10.1097/SLA.0000000000002356. Erratum in: Ann Surg. 2018 Mar;267(3):e64. PMID: 28795993; PMCID: PMC5629006.
• Ehrlich PF, Chi YY, Chintagumpala MM, Hoffer FA, Perlman EJ, Kalapurakal JA, Tornwall B, Warwick A, Shamberger RC, Khanna G, Hamilton TE, Gow KW, Paulino AC, Gratias EJ, Mullen EA, Geller JI, Grundy PE, Fernandez CV, Dome JS. Results of Treatment for Patients With Multicentric or Bilaterally Predisposed Unilateral Wilms Tumor (AREN0534): A report from the Children's Oncology Group. Cancer. 2020 Aug 1;126(15):3516-3525. doi: 10.1002/cncr.32958. Epub 2020 May 27. PMID: 32459384; PMCID: PMC7769115.

This collection contains data from the National Cancer Institute Clinical Trial NCT00980460, "Risk-Based Therapy in Treating Younger Patients With Newly Diagnosed Liver Cancer." It was sponsored by NCI's Children’s Oncology Group (COG) under study number AHEP0731. This phase III trial studies the side effects and how well risk-based therapy works in treating younger patients with newly diagnosed liver cancer. Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive.

Trial Description

Surgery, chemotherapy drugs (cancer fighting medicines), and when necessary, liver transplant, are the main current treatments for hepatoblastoma. The stage of the cancer is one factor used to decide the best treatment. Treating patients according to the risk group they are in may help get rid of the cancer, keep it from coming back, and decrease the side effects of chemotherapy.

Hepatoblastoma treatment with curative intent requires surgical resection, but only about a third of newly diagnosed patients with hepatoblastoma have resectable disease at diagnosis. Patients who have upfront resection typically receive a total of 4–6 cycles of adjuvant chemotherapy post-surgery, with the combination of cisplatin, fluorouracil, and vincristine. The aim is to investigate whether event-free survival in children with hepatoblastoma who had complete resection at diagnosis could be maintained with two cycles of adjuvant chemotherapy. This multicentre, phase 3 trial was designed to test a risk-based treatment approach for children with hepatoblastoma, to diminish toxicity in low-risk patients, improve survival in intermediate-risk patients, and identify new agents that may be used in high-risk and recurrent patients. Patients were staged for risk classification using the Children’s Oncology Group staging guidelines before the initiation of chemotherapy, with stage IV indicating metastatic disease. Pretreatment extent of disease (PRETEXT) grouping also was performed at the time of diagnosis and with any subsequent abdominal computed tomography or magnetic resonance imaging and was used to guide the surgical management but was not used for risk classification. The response rate and outcome to the combination of vincristine and irinotecan administered in an upfront window to children newly diagnosed with high-risk hepatoblastoma was determined.

For Low-Risk patients CT chest was used for metastatic tumor response assessment. Abdominal Ultrasound was obtained at baseline. For Intermediate- and High-Risk patients abdominal ultrasound, CT and/or MRI was used for primary tumor response assessment and CT chest for metastatic tumor response assessment.

Trial Outcomes

Results of the trial for Low-Risk patients have been reported in the following publication:

Katzenstein, H. M., Langham, M. R., Malogolowkin, M. H., Krailo, M. D., Towbin, A. J., McCarville, M. B., Finegold, M. J., Ranganathan, S., Dunn, S., McGahren, E. D., Tiao, G. M., O’Neill, A. F., Qayed, M., Furman, W. L., Xia, C., Rodriguez-Galindo, C., & Meyers, R. L. (2019). Minimal adjuvant chemotherapy for children with hepatoblastoma resected at diagnosis (AHEP0731): a Children’s Oncology Group, multicentre, phase 3 trial. The Lancet Oncology, 20(5), 719–727. DOI: https://doi.org/10.1016/s1470-2045(18)30895-7. Epub 2019 Apr 8. Erratum in: Lancet Oncol. 2019 May;20(5):e243. PMID: 30975630; PMCID: PMC6499702. Epub 2019 Apr 8. Erratum in: Lancet Oncol. 2019 May;20(5):e243. PMID: 30975630; PMCID: PMC6499702.

This collection contains data from the National Cancer Institute Clinical Trial NCT00118209, "Rituximab and Combination Chemotherapy in Treating Patients With Diffuse Large B-Cell Non-Hodgkin's Lymphoma." It was sponsored by NCI's Alliance for Clinical Trials in Oncology under study number CALGB 50303. This randomized phase III trial is studying rituximab when given together with two different combination chemotherapy regimens to compare how well they work in treating patients with diffuse large B-cell lymphoma. Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive.

Trial Description

This randomized phase III trial studies rituximab when given together with two different combination chemotherapy regimens to compare how well they work in treating patients with diffuse large B-cell non-Hodgkin's lymphoma. Monoclonal antibodies, such as rituximab, may block cancer growth in different ways by targeting certain cells. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving rituximab together with combination chemotherapy may kill more cancer cells. It is not yet known which combination chemotherapy regimen is more effective when given with rituximab in treating diffuse large B-cell non-Hodgkin's lymphoma.

Alliance/CALGB 50303 (NCT00118209), an intergroup, phase III study, compared dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) with standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) as frontline therapy for diffuse large B-cell lymphoma. Patients received six cycles of DA-EPOCH-R or R-CHOP. The primary objective was progression-free survival (PFS); secondary clinical objectives included response rate, overall survival (OS), and safety. Between 2005 and 2013, 524 patients were registered; 491 eligible patients were included in the final analysis. Most patients (74%) had stage III or IV disease; International Prognostic Index (IPI) risk groups included 26% IPI 0 to 1, 37% IPI 2, 25% IPI 3, and 12% IPI 4 to 5. At a median follow-up of 5 years, PFS was not statistically different between the arms (hazard ratio, 0.93; 95% CI, 0.68 to 1.27; P = .65), with a 2-year PFS rate of 78.9% (95% CI, 73.8% to 84.2%) for DA-EPOCH-R and 75.5% (95% CI, 70.2% to 81.1%) for R-CHOP. OS was not different (hazard ratio, 1.09; 95% CI, 0.75 to 1.59; P = .64), with a 2-year OS rate of 86.5% (95% CI, 82.3% to 91%) for DA-EPOCH-R and 85.7% (95% CI, 81.4% to 90.2%) for R-CHOP. Grade 3 and 4 adverse events were more common (P < .001) in the DA-EPOCH-R arm than the R-CHOP arm, including infection (16.9% v 10.7%, respectively), febrile neutropenia (35.0% v 17.7%, respectively), mucositis (8.4% v 2.1%, respectively), and neuropathy (18.6% v 3.3%, respectively). Five treatment-related deaths (2.1%) occurred in each arm.

CT scans of the chest, abdomen and pelvis were utilized for tumor staging for 155 of these patients. Serial fluorodeoxyglucose positron emission tomography (FDG-PET) was conducted at baseline, after 2 cycles of chemotherapy (interim PET [i-PET]), and at end of treatment (EoT) to identify biomarkers of response that are predictive of remission and survival.

Trial Outcomes

Results of the trial have been reported in the following publications:

1. Schöder, H., Polley, M.-Y. C., Knopp, M. V., Hall, N., Kostakoglu, L., Zhang, J., Higley, H. R., Kelloff, G., Liu, H., Zelenetz, A. D., Cheson, B. D., Wagner-Johnston, N., Kahl, B. S., Friedberg, J. W., Hsi, E. D., Leonard, J. P., Schwartz, L. H., Wilson, W. H., & Bartlett, N. L. (2020). Prognostic value of interim FDG-PET in diffuse large cell lymphoma: results from the CALGB 50303 Clinical Trial. Blood, 135(25), 2224–2234. https://doi.org/10.1182/blood.2019003277. PMID: 32232481; PMCID: PMC7316220.
2. Bartlett, N. L., Wilson, W. H., Jung, S.-H., Hsi, E. D., Maurer, M. J., Pederson, L. D., Polley, M.-Y. C., Pitcher, B. N., Cheson, B. D., Kahl, B. S., Friedberg, J. W., Staudt, L. M., Wagner-Johnston, N. D., Blum, K. A., Abramson, J. S., Reddy, N. M., Winter, J. N., Chang, J. E., Gopal, A. K., … Leonard, J. P. (2019). Dose-Adjusted EPOCH-R Compared With R-CHOP as Frontline Therapy for Diffuse Large B-Cell Lymphoma: Clinical Outcomes of the Phase III Intergroup Trial Alliance/CALGB 50303. Journal of Clinical Oncology, 37(21), 1790–1799. DOI: https://doi.org/10.1200/jco.18.01994. Epub 2019 Apr 2. PMID: 30939090; PMCID: PMC6774813.

ACRIN 6657 was designed as a prospective study to test MRI for ability to predict response to treatment and risk-of-recurrence in patients with stage 2 or 3 breast cancer receiving neoadjuvant chemotherapy (NACT). ACRIN 6657 was conducted as a companion study to CALGB 150007, a correlative science study evaluating tissue-based biomarkers in the setting of neoadjuvant treatment of breast cancer. Collectively, CALGB 150007 and ACRIN 6657 formed the basis of the multicenter Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging and moLecular Analysis (I-SPY TRIAL) breast cancer trial, a study of imaging and tissue-based biomarkers for predicting pathologic complete response (pCR) and recurrence-free survival (RFS). Additional information about the trial is available in the Study Protocol and Case Report Forms.

Participant Eligibility and Enrollment: Criteria for inclusion were patients enrolling on CALGB 150007 with T3 tumors measuring at least 3 cm in diameter by clinical exam or imaging and receiving neoadjuvant chemotherapy with an anthracycline-cyclophosphamide regimen alone or followed by a taxane. Pregnant patients and those with ferromagnetic prostheses were excluded from the study. The study was open to enrollment from May 2002 to March 2006. 237 patients were enrolled, of which 230 met eligibility criteria.

I-SPY 2 (Investigation of Serial studies to Predict Your Therapeutic Response with Imaging And moLecular analysis 2) is an ongoing, multi-center trial (NCT01042379) designed to quickly evaluate the efficacy of new agents for breast cancer in neoadjuvant chemotherapy (NAC) setting. Women aged ≥18 years diagnosed with locally advanced breast cancer (tumor size ≥2.5 cm) without distant metastasis are eligible to enroll in the trial. Patients with breast cancer at high-risk for recurrence are adaptively-randomized to either control arm (standard NAC) or one of several concurrent experimental drug arms. I-SPY 2 utilizes change in tumor volume by DCE-MRI at serial time-points during NAC to adjust the randomization schema as the trial proceeds, preferentially assigning patients to receive agents showing an increasing likelihood of efficacy against their breast cancer subtype. I-SPY 2 opened in Spring 2010 and is ongoing.

This collection includes DCE MRI data (original acquired images and derived parametric maps) for I-SPY 2 patients adaptively randomized between 2010 and 2016, along with histopathologic outcome data. Breast MRI data in this collection was acquired prospectively at over 22 clinical centers using a standardized image acquisition protocol. Patients underwent 4 MRI exams before and during NAC and over 95% of the DCE imaging data met acceptance criteria for analysis of functional tumor volume (FTV), a demonstrated quantitative imaging marker of breast cancer response to NAC. This is a comprehensive, highly curated imaging data set with histopathologic outcome that can be used to develop, test and compare imaging metrics and prediction models for breast cancer response to treatment. Original but uncurated T2_weighted MRI images are also included for most studies.

719 patients are included in this collection. In combination with 266 patients from the ACRIN 6698/I-SPY2 Breast DWI Collection these 985 patients comprise "I-SPY2 Imaging Cohort 1", the 1st subgroup of publicly released imaging data from the I-SPY 2 TRIAL. All subjects in the I-SPY2 Imaging Cohort 1 were enrolled in I-SPY 2 from 2010 to 2016 and randomized to one of nine completed experimental drug arms or control arm. In order to obtain the MRI data for the entire I-SPY2 Imaging Cohort 1 please download using the manifest file provided in the Data Access table below as this will include the patients from both collections. Downloading this collection alone will result in an incomplete cohort of 719 patients and any results from that patient set will not be comparable to published results from the trial.

In addition, a retrospective study using a 384 patient subset (median age: 49 y/o) was performed to test if prediction models combining multiple MRI features outperform models with single features. Four features were quantitatively calculated in each MRI exam: functional tumor volume, longest diameter, sphericity, and contralateral background parenchymal enhancement. Logistic regression analysis was used to study the relationship between MRI variables and pathologic complete response (pCR). Predictive performance was estimated using the area under the receiver operating characteristic curve (AUC). The cohort was stratified by hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status (positive or negative). Results showed analysis with combined features achieved higher AUCs than analysis with any feature alone. These results are further described in the associated publication and in the multi-feature MRI spreadsheet included with this Collection.

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I-SPY2 Imaging Biomarker Group

We are establishing the I-SPY 2 ​Imaging ​Biomarker ​Subgroup to provide a forum where imaging scientists and radiologists can explore,​ discuss, and strategize on the use of I-SPY 2 MRI data ​available through TCIA. ​Please access https://forms.office.com/r/u0xzwB9kbU to be considered to join our bimonthly Zoom meeting invite list.

The American College of Radiology Imaging Network (ACRIN) trial 6698 (NCT01564368) was a multi-center study to evaluate the effectiveness of quantitative diffusion weighted imaging (DWI) for assessing breast cancer response to neoadjuvant chemotherapy (NAC). ACRIN 6698 was performed as a sub-study of the ongoing I-SPY 2 TRIAL (Investigation of Serial studies to Predict Your Therapeutic Response with Imaging And moLecular Analysis 2), an adaptive, multi-agent phase II trial designed to quickly identify new agents for breast cancer.

Patients recruited for the I-SPY 2 TRIAL and enrolling at sites meeting DWI qualification requirements were eligible for the 6698 trial. 406 women with invasive breast cancer were prospectively enrolled to ACRIN 6698 at ten institutions between August 2012 to January 2015, and 272 were randomized to I‑SPY 2 experimental treatment or control arms. Patients underwent breast DWI using a 4-b value protocol, as well as standard T2-weighted and dynamic contrast enhanced (DCE) scans. MRI studies were conducted at 4 timepoints over the course of NAC: pre-treatment (T0), early-treatment after 3 cycles paclitaxel (T1), mid-treatment between paclitaxel and AC (T2) and post-treatment (T3). Of the 272 treated patients, 242 comprised the primary analysis cohort (30 were excluded for missing or non-evaluable DWI exams). This TCIA collection includes all MRI studies received by the UCSF image analysis lab, excluding studies with no analyzable acquisitions. A separate download option is provided to access only those studies in the primary analysis cohort. In addition, DWI test/retest data acquired at baseline or early-treatment in a subset of patients is included in the full collection and is available as a separate download option (N=89 subjects consented and imaged, 71 analyzable test/retest acquisition pairs).

The ACRIN 6698 image data set is currently a unique collection for investigating the utility of DWI for monitoring of response to neoadjuvant breast cancer treatment. While many smaller and/or single-site DWI studies have been published, the multi-center and quality-control aspects of this data allow investigators true evaluation of analysis techniques in the clinical trial environment. The multi-b value protocol also allows evaluation of higher order diffusion models and evaluation at two different clinically relevant b values (600 and 800 s/mm²). Furthermore, the embedded test-retest arm of the study will allow evaluation of repeatability and reproducibility of new DWI metrics and analysis techniques.

In addition to the original DWI data the collection includes derived ADC maps with manually delimited tumor segmentations from the primary study analysis (for all studies rated as analyzable in the QC evaluation), plus T2-weighted images, DCE images with derived enhancement maps, clinical data and outcome data (pathologic complete response [pCR] at surgery). Additional information about the trial is available in the Study Protocol and Case Report Forms.

The objective of the ACRIN 6688 multi-center clinical trial was to correlate changes measured by ¹⁸F-FLT PET imaging, a measure of cellular proliferation, in the primary tumor early during NAC (neo-adjuvant chemotherapy) with pCR (pathologic complete response) in locally advanced breast cancer patients. The trial also examined both pre-therapy and post-therapy association of ¹⁸F-FLT uptake with the tissue proliferative marker Ki-67 to compare ¹⁸F-FLT PET/CT against an accepted reference standard for cellular proliferation. The trial protocol is graphically described in the figure below. Additional information about the trial is available in the Study Protocol and Case Report Forms.

Potentially three ¹⁸ FLT/CT imaging sessions would be conducted at the times indicated above for the 90 enrolled patients on the study. However, only 43 patients completed all three scans, 54 patients had pre/post therapy scans of which 51 were evaluable for the primary aim (see Kostakaglu et al. 2015 ).

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RTOG 0625/ACRIN 6677 is a multicenter, randomized, phase II trial of bevacizumab with irinotecan or temozolomide in recurrent glioblastoma (GBM). This study investigated whether early posttreatment progression on FLAIR or postcontrast MRI assessed by central reading predicts overall survival (OS).

METHODS:

Of 123 enrolled patients, 107 had baseline and at least 1 posttreatment MRI. Two central neuroradiologists serially measured bidimensional (2D) and volumetric (3D) enhancement on postcontrast T1-weighted images and volume of FLAIR hyperintensity. Progression status on all posttreatment MRIs was determined using Macdonald and RANO imaging threshold criteria, with a third neuroradiologist adjudicating discrepancies of both progression occurrence and timing. For each MRI pulse sequence, Kaplan-Meier survival estimates and log-rank test were used to compare OS between cases with or without radiologic progression.

Two sets of XLS spreadsheets (ACRIN-DSC-MR-Brain TCIA Anonymized and ACRIN-DSC-MR-Brain-HB TCIA Anonymized) are needed in order to obtain the entire clinical data set for this collection. The file sets are a random sample of ACRIN 6677 participants divided into 2 groups. Group 1/ACRIN-DSC-MR-Brain TCIA Anonymized: a 75% random sample; Group 2/ACRIN-DSC-MR-Brain-HB TCIA Anonymized: a 25% random sample initially held for testing/validating algorithms trained on the 75% sample. Both are available via the clinical download button.

RESULTS:

Radiologic progression occurred after 2 chemotherapy cycles (8 weeks) in 9 of 97 (9%), 9 of 73 (12%), and 11 of 98 (11%) 2D-T1, 3D-T1, and FLAIR cases, respectively, and 34 of 80 (43%), 21 of 58 (36%), and 37 of 79 (47%) corresponding cases after 4 cycles (16 weeks). Median OS among patients progressing at 8 or 16 weeks was significantly less than that among nonprogressors, as determined on 2D-T1 (114 vs 278 days and 214 vs 426 days, respectively; P < .0001 for both) and 3D-T1 (117 vs 306 days [P < .0001] and 223 vs 448 days [P = .0003], respectively) but not on FLAIR (201 vs 276 days [P = .38] and 303 vs 321 days [P = .13], respectively).

CONCLUSION:

Early progression on 2D-T1 and 3D-T1, but not FLAIR MRI, after 8 and 16 weeks of anti-vascular endothelial growth factor therapy has highly significant prognostic value for OS in recurrent GBM.