Amendment2.pdf

OMB No 0990-0115

1. CONTRACT ID CODE PAGE OF PAGES

AMENDMENT OF SOLICITATION/MODIFICATION OF CONTRACT N/A 1 34

2. AMENDMENT/MODIFICATION NO. 3. EFFECTIVE DATE 4. REQUISITION/PURCHASE REQ. NO. 5. PROJECT NO. (If applicable)

0002 May 16, 2014 N/A

6. ISSUED BY CODE 7. ADMINISTERED BY (If other than Item 6) CODE N/A National Institutes of Health National Cancer Institute Office of Acquisitions 9609 Medical Center Dr Rockville, MD 20850

8. NAME AND ADDRESS OF CONTRACTOR (No. Street, County, State and ZIP: Code) () 9A. AMENDMENT OF SOLICITATION NO.

TO ALL POTENTIAL OFFERORS

N02CP41010-32

9B. DATED (SEE ITEM 11)

April 24, 2014

10A. MODIFICATION OF CONTRACT/ORDER NO.

10B. DATED (SEE ITEM 13)

CODE FACILITY CODE

11. THIS ITEM ONLY APPLIES TO AMENDMENTS OF SOLICITATIONS

The above numbered solicitation is amended as set forth in Item 14. The hour and date specified for receipt of Offers is extended, is not extended.

Offers must acknowledge receipt of this amendment prior to the hour and date specified in the solicitation or as amended, by one of the following methods:

(a) By completing Items 8 and 15, and returning one (1) copy of the amendment; (b) By acknowledging receipt of this amendment on each copy of the offer submitted;

or (c) By separate letter or telegram which includes a reference to the solicitation and amendment numbers. FAILURE OF YOUR ACKNOWLEDGMENT TO BE RECEIVED AT THE PLACE DESIGNATED FOR THE RECEIPT OF OFFERS PRIOR TO THE HOUR AND DATA SPECIFIED MAY RESULT IN REJECTION OF YOUR OFFER. If by virtue of this amendment you desire to change an offer already submitted, such change may be made by telegram or letter, provided each telegram or letter makes reference to the solicitation and this amendment, and is received prior to the opening hour and data specified.

12. ACCOUNTING AND APPROPRIATION DATA (If required)

13. THIS ITEM APPLIES ONLY TO MODIFICATIONS OF CONTRACTS/ORDERS,

IT MODIFIES THE CONTRACT/ORDER NO. AS DESCRIBED IN ITEM 14.

() A. THIS CHANGE ORDER IS ISSUED PURSUANT TO: (Specify authority) THE CHANGES SET FORTH IN ITEM 14 ARE MADE IN THE CONTRACT ORDER NO. IN ITEM 10A.

B. THE ABOVE NUMBERED CONTRACT/ORDER IS MODIFIED TO REFLECT THE ADMINISTRATIVE CHANGES (such as changes in paying office, appropriation date, etc.) SET

FORTH IN ITEM 14, PURSUANT TO THE AUTHORITY OF FAR 43.103(b).

C. THIS SUPPLEMENTAL AGREEMENT IS ENTERED INTO PURSUANT TO AUTHORITY OF:

D. OTHER (Specify type of modification and authority)

E. IMPORTANT: Contractor is not, is required to sign this document and return copies to the issuing office.

14. DESCRIPTION OF AMENDMENT/MODIFICATION (Organized by UCF section headings, including solicitation/contract subject matter where feasible.)

PURPOSE: To provide questions and answers and amend Appendix A, Attachment 11, and Attachment 18.

Deadline for Questions: May 9, 2014; 10AM (Local Time, Rockville, MD) (Unchanged)

Proposal Due Date: May 28, 2014; 10AM (Local Time, Rockville, MD) (Unchanged)

Except as provided herein, all terms and conditions of the document referenced in Item 9A or 10A, as heretofore changed, remains unchanged and in full force and effect.

15A. NAME AND TITLE OF SIGNER (Type or print) 16A. NAME AND TITLE OF CONTRACTING OFFICER (Type or print)

15B. CONTRACTOR/OFFEROR 15C. DATE SIGNED 16B. UNITED STATES OF AMERICA 16C. DATE SIGNED

(Signature of person authorized to sign)

BY _____________________________________________

(Signature of Contracting Officer)

NSN 7540-01-152-8070 30-105 STANDARD FORM 30 (REV. 10-83)

PREVIOUS EDITION UNUSABLE Computer Generated Prescribed by GSA

FAR (48 CFR) 53.243

RFP N02CP41010-32 Questions and Answers Amendment 2 Page 1 of 4

NATIONAL CANCER INSTITUE

N02CP41010-32

QUESTIONS AND ANSWERS

The following are answers to questions received from potential offerors.

Q8: Is an IDIQ-level budget totaling to the 65,400 labor hours over five years required or just the specific sample task budgets, as specified in the three TO-RFPs? This question has arisen because each of the sample task orders call for a budget covering a shorter performance period (TO1- one month, TO2 - 6 months, TO3 - three years) than the five-year IDIQ period of performance.

A8: Offerors need to submit a budget for the entire 5 year IDIQ period with budgets for each Task Area. Sample Task Orders 1, 2, and 3 should be a part of the overall budget in each respective Task Area.

Q9: Sample Task Order 2 has a six-month period of performance, implying that only a six-month budget is necessary. If that is the case, how do offerors incorporate the additional business proposal costing assumptions that extend beyond a six-month performance period (e.g., 2 pilot studies a year, 4 domestic and five (5) international trips a year)?

A9: Please see answer above.

Q10: Amendment 1 clarifies that a technical discussion of Task Area IV is not required. Please confirm that the hours specified for Task IV on page 47 do not have to be budgeted.

A10: Please see answer above.

Q11: Amendment 1 clarifies the organization of the Sample Task Orders. Is the intent that each Sample Task Order comprises a standalone volume or can these be subsections within a larger technical volume? Related to that, is it permissible for the non-page-limited materials (resumes/CVs, Security Plan, 508 Compliance Plan, etc.) be included as Appendices to the overall technical volume?

A11: Yes. Each Sample Task Order technical proposal can be a part of the overall technical volume. The non-page-limited materials may be included as Appendices to the overall technical volume.

Q12: In describing Sample Task Order 3 activities, is it permissible to reference material included in response to the more expansive Sample Task Order 2 write-up or must all material be self-contained within the sample task order write-ups?

A12: Technical volumes for each Sample Task Order shall be self-contained. They may reference appendices, but they should not reference other Sample Task Orders.

Amendment 2 Page 2 of 4

Q13: Sample Task Order 3 refers offerors to Task Area III instructions for the “entire technical requirement” (pages 14-16 of 26). Should offerors assume that all of the requirements on these pages apply to the Sample Task Order 3 design and should be incorporated as such?

In general, where should offerors discuss Task Area III elements not considered integral to their Sample Task 3 approach?

A13: Offerors should provide a technical proposal in line with the requirements of

Sample Task Order 3. Any outstanding elements in Task Area III that offerors do not feel is covered by Sample Task Order 3 do not need to be addressed.

Q14: Page 47 provides budget hour guidance for four labor categories. “Senior Data Analyst” is not one of these categories, although it is called out in the personnel section. For budget estimation, to which labor category does this role belong (Project Director, Senior Study Manager, Junior Study Manager, or Field/Administrative Support)?

A14: “Senior Data Analyst” falls under the labor category “Senior Study Manager”.

Q15: For transition planning, please provide information about the volume of physical materials that a new contractor would receive during the transition period.

A15: Please see list of turnover material listed under Task Area I.

Q16: Is it possible to provide an English translation of the abstracting manual?

A16: No, an English translation for the Chinese SOP will not be made available. The new

Contractor will have to provide support services to a study in China. It is expected that the new Contractor has the tools necessary to provide the support.

Q17: For planning the receipt of electronic files during the initial transition, can NCI provide more information about the current software the incumbent uses for subject and specimen tracking for this project? Are there systems developed under this contract that a successor will inherit during the transition from the incumbent?

A17: We do not anticipate that the new Contractor will inherit any software from the incumbent Contractor.

Q18: Will NCI consider extending the due date by one week?

A18: No, an extension is not possible.

Q19: If there are no uniform costs assumptions for subcontracts, can you please provide a minimum dollar amount to be included for subcontracts for each of the Task Areas? For example, one of the studies in Sample Task Order 2 is Second Cancers After Breast Cancer in Kaiser HMO. In Appendix A. of the Background Statement, it is indicated that the Contractor shall be the successor in interest for the subcontract with Kaiser HMOs.

Several other subcontracts are mentioned for the ongoing studies addressed in Task Area

Amendment 2 Page 3 of 4

2 and potential subcontracts for the study addressed in Task Area 3. In order to determine the overall proposed costs, please provide the value level to be assigned to the budget for each Task Area.

A19: Please assume a uniform cost assumption for a consultant agreement under USRT’s study for $100,000 per year for the first two years. Please see changes made to Appendix A.

Q20: Attachment 1 indicates that hard copies should be provided for review. Attachment 11, page 1, indicates that documents submitted using Adobe .pdf shall be in a searchable format. Is this a hard copy submission only?

A20: Hard copies shall be provided in accordance with Attachment 1. Additionally, one electronic copy each of proposal (Technical and Business) shall be provided. The electronic copies shall be in Microsoft Word, Portable Document Format (PDF), or Microsoft Excel and shall be provided on a CD. If there is a discrepancy between the hard copy and the electronic copy, the hard copy will prevail.

Q21: RFP page 49, Item 2, indicates that proposals should be printed double-sided on at least

30% post-consumer fiber paper. Attachment 11, page 2 indicates that the proposal should be printed single-sided. Please indicate your preference for printing.

A21: FAR 4.302(b) requires: “When electronic commerce methods (see 4.502) are not used, agencies shall require contractors to submit paper documents to the Government relating to an acquisition printed or copied double-sided on at least 30 percent postconsumer fiber paper whenever practicable. If the contractor cannot print or copy double-sided, it shall print or copy single-sided on at least 30 percent postconsumer fiber paper.”

Q22: RFP page 49, Item 4, indicates that the Attachment 7 Technical Proposal Cost Summary should be included in the Technical proposal. Attachment 11, page 2, Item D, indicates that Attachment 13 NIH 2043 should be included in the Technical proposal. Please confirm Attachment 7 is the correct attachment for the Technical proposal.

A22: Both Attachment 7 and Attachment 13 should be included in the Technical

Proposal.

Q23: RFP page 65, Item 4, indicates that a separate section entitled “Human Subjects” should be included in the technical proposal. Attachment 11 Table of Contents does not list this as a separate section. Should this be included as a separate section of the technical, or included in the appendix along with Attachment 9?

A23: All discussion on Human Subjects should be included as a section in the technical proposal.

Amendment 2 Page 4 of 4

Q24: Section M, page 96, could NCI provide guidance on what should be included in the technical proposal to address the Sustainable Acquisition Plan?

A24: Please see Section I.4.b.a. (page 38 of the RFP) and Attachment 25 “Green

Purchasing Definitions” for further instructions on Sustainable Acquisition Plan.

Q25: Page 39/Attachment 14 requires the submission of a Subcontracting Plan. Since this is an

IDIQ and the tasks and dollar amounts are unknown at this time, may the offeror submit Plans with percentage goals only and use “TBD” where dollar values are required? If not, what contract dollar values, by year, should offerors use in their plans?

A25: Offerors should use dollar values based on their 5-year IDIQ budget proposal.

“TBD” will not be accepted.

Q26: Does NCI wish to receive one technical volume and one business volume covering the

IDIQ and all the sample tasks (2 volumes total), or separate proposal volumes for each sample task, and for the IDIQ?

A26: Offerors should submit one technical volume with sections for each Sample Task

Order, Resumes, Sample Questionnaires, Certificates, SOPs, Health and Safety manual, Letters of Commitment, Human Subjects, Section 508, Sustainability Acquisition Plan, and any other sections necessary. Offerors should submit one business volume with section for cost, past performance, subcontracting plan, SDB plan, and any other sections necessary.

RFP N02CP41010-32 Appendix A & B

Amendment 2 Page 1 of 22

Appendix A.

This appendix includes ongoing and proposed new studies to be supported within the first two years of the new support services contractor, grouped by REB key research areas. The size of the effort by the Contractor is indicated at the end of the descriptive paragraph as:

Small =<$100,000

Medium =≥$100,000-$500,000

Large =≥$500,000

These costs represent the estimated costs needed for support services for each study from contract award to completion of the study or the end of the contract period, whichever comes first.

Ongoing Studies:

Medical Radiation Exposure and Second Cancer Risk

1. Second Cancers After Breast Cancer in Kaiser HMO

Breast cancer survivors now make up about 25% of the 11 million cancer survivors living in the U.S. Evaluation of the role of radiation, chemotherapy, and other factors that could impact their long-term health is of clinical and public health importance. Historically, most studies of these late effects have been case-control studies that have required extensive efforts to reconstruct treatment histories from paper medical records. NCI has been evaluating newer, more cost-effective approaches, and recently completed a pilot study of breast cancer survivors in the Kaiser Northwest HMO. The pilot demonstrated that it was feasible to generate a historical cohort of 4717 breast cancer survivors, diagnosed from 1991 to 2009, with comprehensive exposure information by linking multiple electronic health records that included rich information on treatments (including all hormonal therapy prescriptions, chemotherapies and radiotherapy), smoking histories, height, weight as well as extensive details on the cancer diagnoses and other outcomes. In the past year, NCI added a second cohort of 3646 breast cancer survivors from Kaiser Colorado to create a large cohort of breast cancer survivors (n=8363) with an average of 10 years post-diagnosis follow-up that will enable evaluation of long-term second cancer risks, in particular lung cancer, in relation to a variety of breast cancer therapies and lifestyle variables including obesity and smoking. It is anticipated that the Contractor shall be the successor in interest for the subcontract with

Kaiser HMOs. The Contractor shall coordinate subcontracts with these Kaiser HMOs in order to continue to follow the cohort for the incidence of second cancers survivors and to coordinate the calculation of radiation doses to the lung that the cohort received as part of their breast cancer treatment, as well as provide general oversight and quality control of data received from Kaiser. (Medium)

There are no SOPs available for this study.

2. Second Cancer Risk Following Chemotherapy and Radiotherapy for Retinoblastoma

Since 1984, REB investigators have been evaluating subsequent cancer risk in a unique cohort

Amendment 2 Page 2 of 22 of 2,000 1-year retinoblastoma (Rb) survivors. NCI identified increased risks of second cancers in the cohort that have been attributed to the interaction of radiotherapy and genetic susceptibility. Given the current median age of the Rb cohort (38 yrs), the very high risk for second cancers in patients with hereditary Rb, and the presence of the RB1 mutations in the pathway of several common epithelial adult tumors, and the newer treatments for Rb, NCI plans to continue to follow the cohort over the next decade to quantify cancer risks. The cohort of survivors was interviewed by telephone in 1993, 1998, 2001, and 2009. The most recent National Death Index search was conducted in 2011. Approximately 35% of the cohort has developed a second cancer. All of the second cancers have been confirmed by pathology reports whenever possible. The Contractor shall continue to trace the cohort for vital status and current address and telephone number in case NCI decides to conduct another telephone survey of the cohort. The Contractor shall continue to collect information on second cancers and conduct National Death Index searches, confirm and code second cancers, update the study cohort files and prepare analytic data files.

(Medium)

The following SOPs are available: (located after Appendix B)

Medical Record Abstraction Form

Training Manual for Abstractors

Questionnaire

Cancer Confirmation Process

Occupational Radiation Exposure

3. U. S. Radiologic Technologist (USRT) Cohort studies: Dose Reconstruction: Nuclear

Medicine Technologists and Technologists Performing/ Assisting with Fluoroscopically-

Guided Procedures

The USRT study began in 1984 by NCI and is a nationwide retrospective cohort of 146,020 radiologic technologists who were certified between 1926 and 1984. Four surveys have been conducted in this cohort to ascertain work history, medical history, and various cancer risk factors, such as lifetime UV exposure. A major emphasis during the last few years has been a retrospective dose reconstruction to assign estimated annual and cumulative occupational radiation doses to individual technologists to assess occupational radiation-related dose-response patterns. However, absorbed doses to the technologists who assist with nuclear medicine (NM) procedures may be higher than those of other radiologic technologists, because radionuclides have much higher energies with greater tissue penetration than lower energy x- or γ-rays. Similarly, doses may be substantially higher for technologists who assist with fluoroscopically-guided interventional (FG) procedures due to the type and length of the procedures compared with radiography procedures. NCI is currently collecting additional work history information to improve dose estimation for workers who performed NM and

FG procedures. REB dosimetrists will develop detailed estimation of annual and cumulative dose estimates for radiologic technologists in the cohort whose occupational history indicates primarily working in NM or assisting or performing FG procedures. It is anticipated that the Contractor shall be the successor in interest for the subcontract with USRT. The

Contractor shall support expert dosimetry and statistical consultants and update vital status and film badge dose data through linkage with the American Association of

Amendment 2 Page 3 of 22

Radiologic Technologists and a commercial dosimetry company. (Medium)

There are no SOPs available for this study. The Contractor shall provide mathematical, scientific and computer consulting/support for epidemiologic research for REB. The

Contractor shall work directly with REB staff and others on various aspects of the analysis and management of data from the x-ray technologists study. A particular emphasis on this work will be the development and practical implementation of statistical methods to incorporate information on dosimetric uncertainty.

Environmental Radiation Exposure

4. Dose Reconstruction and Health Effects of In-utero and Early-life Radiation Exposure

(Chernobyl-related studies)

NCI is currently collaborating with investigators in Belarus to establish a cohort of about

2,500 individuals exposed in utero and in early life to radioactive iodine and other radioactive isotopes from Chernobyl fallout, reconstructing doses to the thyroid gland from internal and external radiation exposure, ascertaining thyroid cancer and other thyroid diseases and assessing radiation dose-responses for these endpoints. NCI is working with the collaborators to locate cohort subjects, interview their mothers, collect personal information on places and dates of residence, consumption of local foodstuff, countermeasures applied

(e.g., administration of stable iodine), time spent outdoors, construction materials of houses, etc., as well as specifics regarding the timing of the pregnancy during the period of exposure.

NCI will use this information for dose reconstruction. Measurements of 131-I content in the mother’s thyroid gland have been made and they will be linked to subjects to reconstruct fetal thyroid dose. Comprehensive dose reconstruction will take into account both internal and external sources of irradiation. The collaborators will ascertain thyroid cancer by linking the cohort with the Belarus National Cancer Registry. The Contractor shall be the liaison between the local public health officials in Belarus who are collaborating on this project. The Contractor shall coordinate the various phases of this project to assist with data management, pre-test questionnaires as needed, and ensure that milestones are met in a timely fashion and within budget and ship tissue specimens (about 100) to a

NCI designated laboratory for analysis. (Medium)

There are no SOPs available for this study. The Contractor shall provide support on computer codes for calculating thyroid doses due to iodine-131 intakes using a published dosimetry model. The Contractor shall adapt information obtained from Iodine-131 and

Cesium-137 deposition and questionnaire data and run computer code to calculate instrumental and ecological doses to the thyroid for cohort members. The Contractor shall obtain reliable central estimates and stochastic thyroid doses due to exposure to Iodine-131 for cohort members. To evaluate the feasibility of data collection for military clean-up workers, the Contractor shall collect data with detailed descriptions of ‘clean-up’ activities for military clean-up workers including results of direct thyroid measurements that were taken shortly after the Chernobyl accident in 1986.

Amendment 2 Page 4 of 22

Dosimetry Studies

5. Medical Radiation Dosimetry for Epidemiologic Studies In order to quantify the risk of cancer in populations exposed to ionizing radiation, REB investigators frequently require accurate estimates of organ-specific radiation dose in large numbers of individual study subjects in order to estimate dose-response relationships.

Dosimetry support will include making measurements on anthropomorphic/water/other phantoms, abstracting information on radiotherapy in medical records, calculating radiation doses to organs of interest as well as uncertainties in these dose estimates, and providing advice in support of pilot studies on the quality of radiotherapy data and probable estimates or organ doses for specific radiation exposures. An example of future REB-led project that shall require dosimetry support is Kaiser Permanente Health Plan Study to examine the long-term cancer risks of breast cancer treatments in a cohort of 8000 women. It is anticipated that the Contractor shall be the successor in interest for the subcontract with Kaiser. Another example is an ongoing study of gene-radiation interactions on second cancer risk in the Childhood Cancer Survivor Cohort (CCSS).

The Contractor shall provide dosimetry support for approximately 500 survivors for

CCSS. The Contractor shall work closely with extramural medical physicists and other dosimetry staff to provide support for a program of dose estimation for REB’s ongoing and new epidemiologic studies. (Large)

There are no SOPs available for this study. The Contractor provides services to support REB research activities in the area of radiation dosimetry in support of health risk studies.

6. Support state-of-the-art computer program for individual organ dose calculations from radiological accidents or terrorist events REB is currently developing a computer program for external organ dose estimations for individuals that might be exposed to photon radiation from radiological accidents, emergencies, or terrorist activities. The software program will include three components: (1) a Monte Carlo radiation transport code especially designed for human anatomy with relatively simple radiation field geometries, (2) realistic human anatomical models ranging from newborn to adult males and females that are flexible enough to represent any posture and body size of interest during exposure, and (3) a graphical user interface (GUI) for the user to specify the type and geometry of the radiation source and to specify simple shielding geometries that might have protected the person during exposure, and to conveniently calculate absorbed doses to individual organs. The software will calculate absorbed doses to organs through radiation transport simulations. The Contractor shall coordinate with consultants to test the software as it proceeds through stages including testing support of the Monte Carlo code, the GUI, and extensive comparison to other dose estimation tools as well as support of experimental validation. The Contractor shall also ensure that testing milestones are met on time and within budget. (Small-Medium)

There are no SOPs available for this study.

Amendment 2 Page 5 of 22

Multi-center Studies

7. InterLymph Subtypes International Project

Non-Hodgkin lymphoma (NHL), which affects over 86,000 individuals in the United States annually, is composed of numerous closely-related yet heterogeneous diseases with distinctive morphologic, immunophenotypic, genetic, and clinical features. Because individual epidemiologic studies do not have sufficient sample size to evaluate risk factors by

NHL subtype, the International Lymphoma Epidemiology Consortium (InterLymph) has undertaken a consortium-wide initiative, the “InterLymph NHL Subtypes Project” with the primary aims of 1) comprehensively evaluating risk factor profiles across NHL subtypes in a multivariate setting, and 2) quantitatively assessing etiologic heterogeneity across NHL subtypes. The project pools individual-level data on over 15 lifestyle, medical history, family history, and occupational risk factors from 20 case-control studies across North

America, Europe, and Australia, including a total of 17,564 NHL cases and 24,109 controls. Data are being analyzed centrally and will be published as 13 manuscripts in a special issue of a journal. The Contractor shall provide logistical support by organizing email communications amongst over 50 collaborators on 3 continents, including scheduling and coordinating approximately 2 teleconferences per year as needed, preparing and distributing teleconference notes to all participants, and tracking key study tasks. (Small)

The following SOPs are available: (located after Appendix B)

List of collaborators

Monograph proposal

8. Periconception Folic Acid Supplements and Other Postulated Risk Factors for Pediatric

Leukemia and Other Childhood Cancers: A Record-Linkage Study in a Chinese Cohort

The Chinese Center for Disease Control and Prevention (CCDC), the National Cancer

Institute (NCI), and U.S. Centers for Disease Control and Prevention (CDC) investigators will evaluate prospectively the role of periconception folic acid supplements and other postulated risk factors in risk of developing pediatric leukemia and other cancers. This study, the Children and Families Cohort Study (CFCS), will be carried out in a unique population of offspring of Chinese mothers who were enrolled during 1993-95 in a large (N=243,779)

Community Intervention Program (CIP) of periconception folic acid supplements. The

Contractor shall coordinate the various phases of this project to oversee data collection, assist with data management, and ensure that milestones are met in a timely fashion and within budget. A pilot study is now underway to determine if a main study is feasible. The aims for the pilot study include identifying and abstracting medical records for 1) all pediatric cancer cases in children born during 1994-96 and diagnosed in the 8 pilot study hospitals during 1994 to the present, (2) all pediatric cancer cases or related disorders that are incompletely worked up for diagnosis of pediatric cancer and/or completely worked up but not treated among children born during 1994-96. The aims of the Main Study are: (1) to compare risk of pediatric leukemia, brain tumors, and other cancers diagnosed in offspring of mothers who took versus did not take folic acid supplements during the peri-conception/early first trimester period based on the

1993-95 CIP records and (2) to assess prospectively postulated prenatal, early neonatal, Amendment 2 Page 6 of 22 and pre-conception risk factors for pediatric leukemias, brain tumors, and all cancers combined in the CFCS cohort using interview data collected from mothers and medical records during 1993-96 in a hospital and community-based component. (Medium)

The following SOP is available: (located after Appendix B)

Chinese language data manual

NEW STUDIES

1. Second Cancer Risks after Intensity Modulated Radiation Therapy and Proton

Therapy Intensity modulated radiation therapy (IMRT) is a newer and rapidly expanding approach to the planning and delivery of radiotherapy. IMRT allows dose to be concentrated in the tumor volume and so should result in better tumor control and reduction of acute toxic effects in surrounding organs. However, because more monitor units and more fields are used than in conventional radiotherapy the result is a larger total-body radiation dose and dose to organs outside the radiation fields. Hence, the reduction in acute toxic effects may be at the cost of increased risks of second malignancies. To date there have been no direct studies of the long-term second cancer risks from IMRT use. Proton therapy is also rapidly expanding and many similar concerns exist for this alternative therapy, especially exposure to neutrons as a by-product. NCI plans to conduct feasibility work to explore strategies for constructing a cohort of patients treated with these conventional and newer therapies in the U.S and to estimate doses. The Contractor shall conduct feasibility work including evaluation of treatment data completeness at state cancer registries and extraction of samples of medical and radiotherapy records. For these efforts the Contractor shall develop coding and data extraction forms. (Large)

2. Cancer in Solid Organ or Bone Marrow Transplant Patients – Expansion with More

Recently Treated Patients

Patients undergoing bone marrow transplantation (BMT) are of particular interest due to their unusual combination of exposures, including total body irradiation with 8-15 Gy, intensive chemotherapy, and late complications of severe immune dysfunction. To address the late carcinogenic effects of high dose radiotherapy in the presence of severe immune dysfunction, NCI assembled an international cohort of nearly 29,000 patients who received allogeneic

BMT between 1964 and 1996 at 272 transplant centers worldwide. NCI proposes to (1) conduct a feasibility study to assemble a new cohort that will evaluate new transplantation procedures and (2) increase follow-up for new malignancies for the existing cohort through

2004. There are several novel areas of study that NCI proposes to add during the expansion of this cohort, including evaluation of the relation between viral infections (e.g., cytomegalovirus) and subsequent malignancies, and a study to assess the feasibility of collecting biospecimens for future studies of genetic susceptibility to malignancies following transplantation. The Contractor shall conduct feasibility work and coordinate a follow-up of this cohort. (Medium)

3. A Pilot Study for a US Biobank Cohort Using HMOs

Many of the existing etiology cohorts in NCI are now 15-20 years past their initial baseline, Amendment 2 Page 7 of 22 have limited remaining biologic samples and are aging. There is the need, therefore, to start investigating settings for a new generation of cohorts that could answer a broad range of etiology questions and include multiple biologic samples for longitudinal molecular studies.

The HMOs provide a rich potential setting for such a cohort because of the passive follow-up systems via high-quality cancer registries, electronic medical records with data on medications, radiotherapy, co-morbidities and intermediate end-points and centralized laboratories for processing samples. In the next few years, NCI plans to conduct feasibility and then pilot studies for a U.S. biobank cohort within a group of HMOs. This is envisioned to be a Division-wide resource. The Contractor shall help identify collaborating centers, assess the best collection method for biological samples, and conduct pilot work for questionnaire development. If the pilot work is successful, then the Contractor may provide support with similar components of the full study. (Small)

4. U.S. Veterans “Weatherman” Biodosimetry Study

REB will investigate the use of quantitative biodosimetry (biomarkers of radiation exposure, including fluorescent in situ hybridization) for subjects exposed many decades before the assay, as well as summarize the cancer and mortality experience of U.S. veterans with the highest recorded radiation exposures. The proposed study will: (1) Validate the use of biodosimetry for exposures that took place six decades in the past. The exposures are estimated to range from 300 mGy-1 Gy; (2) Compare the biologically-based dose estimates with those from film badges; and (3) Summarize other data for two highly exposed groups of veterans. The subjects of this study will be (i) 9 military air weathermen (9 of 27 are still alive) exposed on Rongerik Atoll in the Pacific in 1954 to fallout from the largest U.S.

nuclear test, and (ii) the 9 living military personnel who were observers to nuclear tests in

1952 at the Nevada Test Site and who received the highest doses according to the Dept. of

Defense (DoD). The Contractor shall manage all aspects of the project. They shall provide support for development of the questionnaire, pre-test the questionnaire, contact subjects and collect questionnaire data and biosamples, and ship samples to a

NCI designated laboratory. The Contractor shall prepare an analytic data file. (Small)

Amendment 2 Page 8 of 22

Appendix B. Bibliography

PUBLICATIONS SINCE THE LAST Senior Advisory Group (SAG) REVIEW

(Period of current contract July 2009- June 2014)

1A. Medical, Diagnostic Radiation

CT Scan Use

1. Berrington de González A, Kim KP, Smith-Bindman R, McAreavey D.

Myocardial perfusion scans: projected population cancer risks from current levels of use in the United States. Circulation. 2010 Dec 7; 122(23):2403-10.

2. Berrington de González A, Kim KP, Yee J. CT colonography: perforation rates and potential radiation risks. Gastrointest Endosc Clin N Am. 2010 Apr; 20(2):279-

91.

3. Berrington de González A, Kim KP, Knudsen AB, Lansdorp-Vogelaar I, Rutter

CM, Smith-Bindman R, Yee J, Kuntz KM, van Ballegooijen M, Zauber AG, Berg

CD. Radiation-related cancer risks from CT colonography screening: a risk-benefit analysis. AJR Am J Roentgenol. 2011 Apr; 196(4):816-23.

4. Berrington de González A, Mahesh M, Kim KP, Bhargavan M, Lewis R, Mettler

F, Land C. Projected cancer risks from computed tomographic scans performed in the United States in 2007. Arch Intern Med. 2009 Dec 14; 169(22):2071-7.

5. Berrington de González A. Estimates of the potential risk of radiation-related cancer from screening in the UK. J Med Screen. 2011; 18(4):163-4.

6. Kim KP, Einstein AJ, Berrington de González A. Coronary artery calcification screening: estimated radiation dose and cancer risk. Arch Intern Med. 2009 Jul 13;

169(13):1188-94.

7. Linet MS, Slovis TL, Miller DL, Kleinerman R, Lee C, Rajaraman P, Berrington de González A. Cancer risks associated with external radiation from diagnostic imaging procedures. CA Cancer J Clin. 2012; 62:75-100.

Conference on Radiation and Health

8. Stram D, Puskin, J, Redpath, L, Kronenberg A, Brooks T, Schubauer-Berigan M, Preston D, Kleinerman RA, Sigurdson A, Zablotska L, Ronckers C, Colman M, Little M. New developments and future directions in radiation research American

Statistical Association Conference on radiation and health. Vail, Colorado, June15-

18, 2008. Radiation Research. 2010; 173, 392-398.

9. Stram D, Sigurdson A, Schubauer-Berigan M, Darby S, Zimbrick J, Colman M, Bhatti P, Cullings H, Kronenberg A, Amundson S, Jacob P, Puskin J. Radiation exposure in medicine: biological and public health significance American Statistical

Association Conference on radiation and health. Annapolis, Maryland, June 13-16, 2010. Radiation Research. 2011; 175, 131-142.

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Scoliosis Study

10. Ronckers CM, Land CE, Miller JS, Stovall M, Lonstein JE, Doody MM. Cancer mortality among women frequently exposed to radiographic exams for spinal disorders. Radiat Res. 2010; 174(1):83-90.

1B. Medical, Therapeutic Radiation

Benign Gynecologic Disorders

11. Sakata R, Mabuchi K, Kleinerman RA, Stovall M, Smith SA, Thompson WD, Wactawski-Wende J, Cookfair DL, Hadjimichael O, Boice JD Jr, Inskip PD.

Cancer mortality following radiotherapy for benign gynecological disorders. Radiat

Res, 2012, 178;266-79.

Retinoblastoma Survivors

12. Bhagia P, Colanta A, Abramson DH, Carlson D, Kleinerman RA, Kraus D, Dunkel I. Sinonasal adenocarcinoma: A rare second malignancy in long-term retinoblastoma survivors. Pediatr Cancer Blood. 2011; 57:693-695.

13. Francis JH, Kleinerman RA, Seddon JM, Abramson DH. Increased risk of secondary uterine leiomyosarcoma in hereditary retinoblastoma. Gynecol Oncol.

2012; 124:254-9.

14. Kleinerman RA, Schonfeld SJ, Tucker MA. Sarcomas in hereditary retinoblastoma. Clinical Sarcoma Review. 2012. Epub ahead of print.

15. Kleinerman RA, Yu CL, Little MP, Li Y, Abramson DH, Seddon JH, Tucker MA.

Variation of second cancer risk by family history among long-term survivors of retinoblastoma. J Clin Oncol. 2012;30:950-957

16. Kleinerman RA, Yu CL, Little MP, Li Y, Abramson DH, Seddon JH, Tucker MA.

Reply to AC Moll, et al. J Clin Oncol. 2012;24:3028-29.

17. Kleinerman RA. Radiation sensitive genetically susceptible pediatric sub-populations. Pediatr Radiol. 2009; 39 (Suppl 1):S27-S31.

18. Liu J, Givi B, Wolden S, Kleinerman RA, Dunkel IJ, Lee N, Shah JP, Abramson

DH, Kraus DH. Secondary skull base malignancies in survivors of retinoblastoma:

The Memorial Sloan Kettering Cancer Center experience. Skull Base Journal. 2011;

21:103-107.

19. Mills MB, Balise RR, Hudgins L, Kleinerman RA. Mutation risk associated with paternal and maternal age in a cohort of retinoblastoma survivors. Hum Mutat.

2012; 131:1115-1122.

20. Yu CL, Tucker MA, Abramson DH, Seddon JM, Stovall M, Fraumeni JF Jr, Kleinerman RA. Cause-specific mortality in long-term survivors of retinoblastoma. J Natl Cancer Inst. 2009:101:581-91.

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Second Gastrointestinal Cancers

21. Chaturvedi AK, Kleinerman RA, Hildesheim A, Gilbert EA, Chen BE, Storm H, Lynch CF, Hall P, Langmark F, Pukkala E, Kaijser M, Andersson M, Fossa S, Joensuu H, Travis LB, Engels EA. Second cancers following squamous cell carcinoma and adenocarcinoma of the cervix. J Clin Oncol, 2009; 27:967-73.

22. Kleinerman RA, Smith SA, Holowaty E, Hall P, Pukkala E, Vaalavirta L, Stovall

M, Weathers R, Gilbert E, Aleman B, Kaijser J, Andersson M, Storm H, Joensuu

H, Lynch CF, Dores GM, Travis LB, Morton LM, Curtis RE. Radiation dose and subsequent risk for stomach cancer in long-term survivors of cervical cancer.

IJROBP. 2012. Submitted.

23. Morton LM, Gilbert E, Hall P, Andersson M, Joensuu H, Dores GM, Stovall M, Holowaty EJ, Lynch CF, Curtis RE, Smith SA, Kleinerman RA, Storm H, Pukkala E, Weathers R, Linet MS, Rajaraman P, Fraumeni JF, Brown LM, van

Leeuwen FE, Fossa SD, Johannesen TB, Langmark F, Travis LB, Aleman B. Risk of treatment-related esophageal cancer among 5-year breast cancer survivors. Ann

Oncol. Epub on line, June 27, 2012.

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24. Lan Q, Zhang L, Shen M, Jo WJ, Vermeulen R, Li G, Vulpe C, Lim S, Re X, Rappaport SM, Berndt SI, Yeager M, Yuenger J, Hayes RB, Linet M, Yin S, Chanock S, Smith MT, Rothman N. Large-scale evaluation of candidate genes identifies associations between DNA repair and genomic maintenance and development of benzene hematotoxicity. Carcinogenesis. 2009;30:50-8.

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CM, Rappaport SM, Hayes RB, Linet MS, Yin S, Smith MT, Rothman N.

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Chernobyl Research Studies

26. Abend M, Pfeiffer RM, Ruf C, Hatch M, Bogdanova TI, Tronko MD, Riecke A, Hartmann J, Meineke V, Boukheris H, Sigurdson A, Mabuchi K, Brenner A.

Iodine-131 dose dependent gene expression in thyroid cancers and corresponding normal tissue following the Chernobyl accident. PlosOne. 2012. In press.

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AV, Zurnadzhy LY, Zablotska L, Tronko MD, Hatch M. NA cohort study of thyroid cancer and other thyroid diseases after the Chernobyl accident:

cytohistopathologic correlation and accuracy of fine-needle aspiration biopsy in nodules detected during the first screening in Ukraine (1998-2000). Cancer

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28. Brenner AV, Tronko MD, Hatch M, Bogdanova TI, Oliynik VA, Lubin JH, Zablotska LB, Tereschenko VP, McConnell RJ, Zamotaeva GA, O'Kane P, http://dceg.cancer.gov/reb/research/ionizing/medical/13 http://dceg.cancer.gov/reb/research/other/4

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131 Dose-response for incident thyroid cancers in Ukraine related to the Chornobyl accident. Environ Health Perspect. 2011;119:933-9.

29. Cahoon EK, Rozhko A, Hatch M, Polyanskaya O, Ostroumova E, Tang M, Nadirov PE, Yauseyenka V, Savasteeva I, McConnell RJ, Pfeiffer RM, Brenner

AV. Factors associated with serum thyroglobulin levels in a population living in

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31. Drozdovitch V, Minenko V, Khrouch V, Leshcheva S, Gavrilin Yu, Khrutchinsky

A, Kukhta T, Kutsen S, Luckyanov N, Shinkarev S, Tretyakevich S, Trofimik S, Voillequé P, Bouville A. Thyroid dose estimates for a cohort of Belarusian children exposed to radiation form the Chernobyl accident. Radiat Res. In press.

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33. Hatch M, Brenner A, Bogdanova T, Derevyanko A, Kuptsova N, Likhtarev I, Bouville A, Tereshchenko V, Kovgan L, Shpak V, Ostroumova E, Greenebaum E, Zablotska L, Ron E, Tronko M. A screening study of thyroid cancer and other thyroid diseases among individuals exposed in utero to iodine-131 from Chernobyl fallout. J Clin Endocrinol Metab 2009;94(3):899-906.

34. Hatch M, Furukawa K, Brenner AV, Olinjyk V, Ron E, Zablotska LB, Terekhova

GM, McConnell RJ, Markov VV, Shpak VM, Ostroumova E, Bouville AC, Tronko M. Prevalence of hyperthyroidism after exposure during childhood or adolescence to radioiodines from the Chornobyl nuclear accident: dose-response results from the Ukrainian-American Cohort study. Radiat Res. 2010

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35. Hatch M, Polyanskaya O, McConnell R, Gong Z, Drozdovitch V, Rozhko A, Prokopovich A, Petrenko S, Brenner A, Zablotska L. Urinary Iodine and Goiter

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36. Khrutchinsky A, Drozdovitch V, Kutsen S, Minenko V, Khrouch V, Luckyanov N, Voilleque P, Bouville A. Mathematical modeling of a survey-meter used to measure radioactivity in human thyroids: Monte Carlo calculations of device response and uncertainties. Appl Radiat Isotopes. 2012;70: 743–751.

37. Khrutchinsky A, Kutsen S, Minenko V, Zhukova O, Luckyanov N, Bouville A, Drozdovitch V. Monte Carlo modeling of beta-radiometer device used to measure milk contaminated as a result of the Chernobyl accident. Appl Radiat Isot. 2009;

67:1089-93.

38. Kryuchkov V, Chumak V, Maceika E, Anspaugh LR, Cardis E, Bakhanova E, Golovanov I, Drozdovitch V, Luckyanov N, Kesminiene A, Voillequé P, Bouville

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39. Leeman-Neill RJ, Brenner AV, Little MP, Bogdanova TI, Hatch M, Zurnadzy

LY, Mabuchi K, Tronko MD, Nikiforov YE. RET/PTC and PAX8/PPARΕγ chromosomal rearrangements in post-Chernobyl thyroid cancer and their association with I-131 radiation dose and other characteristics. Cancer. 2012. In

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Physics. Submitted.

41. Likhtarov I, Kovgan L, Chepurny M, Ivanova O, Boyko Z, Ratia G, Masiuk S, Gerasymenko V, Drozdovitch V, Berkovski V, Hatch M, Brenner A, Luckyanov

N, Voilleque P, Bouville A. Estimation of the thyroid doses for Ukrainian children exposed in utero after the Chernobyl accident. Health Physics 2011;100(6):583-593.

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Chernobyl nuclear power plant. Radiat Environ Biophys 2012;51: 187-93.

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50. Zablotska L, Ron E, Rozhko AV, Hatch M, Polyanskaya ON, Brenner AV, Lubin

JH, Romanov GN, McConnell RJ, O'Kane P, Evseenko VV, Drozdovitch VV, Luckyanov N, Minenko VF, Bouville A, Masyakin V. Thyroid cancer risk in

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51. Zablotska LB, Bazyka D, Lubin JH, Gudzenko N, Little MP, Hatch M, Finch S, Dyagil I, Reiss RF, Chumak VV, Bouville A, Drozdovitch V, Kryuchkov VP, Golovanov I, Bakhanova E, Babkina N, Lubarets T, Bebeshko V, Romanenko A, Mabuchi K. Radiation and the risk of chronic lymphocytic and other leukemias among Chornobyl cleanup workers. Environmental Health Perspectives. 2012. In press.

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Interventional Fluoroscopists

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