SEMINARS

BASIC SCIENCE Role of nuclear receptors in carcinogenesis Hawaii: February 18-19, 2004
	Organizers:	Dr. Frank J. GONZALES Dr. Shigeaki KATO
	Participants:	US- 7 Japan- 6
CLINICAL SCIENCE New Horiizons of Targeted Treatment in Radiation Oncology Kyoto: October 2-4, 2003
	Organizers:	Dr. Ritsuo KOMAKI Dr. Masahiro HIRAOKA
	Participants:	US- 9 Japan- 9
Screening Detected Lung Cancer: Diagnostic, Pathologic and Therapeutic Issues and Approaches to Innovative Research Tokyo: October 30-November 2, 2003
	Organizers:	Dr. Scott SAXMAN Dr. Junji YOSHIDA
	Participants:	US- 6 Japan- 10
EPIDEMIOLOGY/BEHAVIORAL SCIENCE Large Cohort Studies for Molocular Epidemiology San Diego: February 6-7, 2004
	Organizers:	Dr. David J. HUNTER Dr. Kei NAKACHI
	Participants:	US-10 Japan- 8

SEMINAR REPORT
UNDER THE U.S.-JAPAN COOPERATIVE CANCER RESEARCH PROGRAM


1. New Horizons of Targeted Treatment in Radiation Oncology
Period: from October 2 to October 4, 3days
Site: Kyoto Park Hotel (644-2, Sanjuusangen-do Temple, Higashiyama-ku, Kyoto)

Japanese Organizer:
Hiraoka Masahiro
Graduate School of Medicine Kyoto University
Therapeutic Radiology and Oncology
Professor

US Organizer
Komaki Ritsuko
University of Texas MD Anderson Cancer Center
Division of Radiation Oncology
Professor


List of Japanese-side Participants
Tetsuo Akimoto
Instructor
Gunma University

Satoshi Ishikura
Clinical Research Fellow
National Cancer Center Higashi Hospital

Yoko Harima
Associate Professor
Kansai Medical University

Saburo Sone
Professor
Tokushima University

Hiroki Shirato
Associate Professor
Hokkaido University

Norio Mitsuhashi
Profesor
Tokyo Women’s Medical University

Yoshihiro Takai
Associate Professor
Tohoku University

Yutaka Hirokawa
Associate Professor
Hiroshima University

List of US-side Participants
Ritsuko Komaki
Professor
Univ. Texas MD Anderson Cancer Center

James D. Cox
Professor
Univ. Texas MD Anderson Cancer Center

Kian K. Ang
Professor
Univ. Texas MD Anderson Cancer Center

C.Clifton Ling
Professor
Memorial Sloan-Kettering Cancer Center

Alan Pollack
Professor
Fox Chase Cancer Center


Shiao Y. Woo
Professor
Baylor College of Medicine

Catherine C. Park
Assistant Professor
Univ. California San Francisco San Francisco, California

Nancy Lee
Assistant Professor
Univ. California San Francisco San Francisco, California

Cliff K.S.Chao
Assistant Professor
Washington Univ. St Louis, Missouri

Luca Milas
Professor
Univ. Texas MD Anderson Cancer Center

Mack Roach III
Professor
Univ. California San Francisco



Itinerary and Topics

October 2 (Thu.) : Head and Neck Including Brain
	Molecular Predictor and Therapeutic Target in Head and Neck Carcinoma	K. Kian Ang
	Improvement in Therapeutic Ratio for Head and Neck Cancers by Chemoradiotherapy and IMRT	Yasumasa Nishimura
	C225 & radiotherapy; targeting treatment to EGFR-antibody in head & neck cancer	Luca Milas
	Continuous superselective intraarterial chemotherapy combined with radiotherapy for head and neck cancer	Nobukazu Fuwa
	IMRT for Nasopharyngeal Tumors	Nancy Lee
	The use of Intensity Modulated Radiation Therapy in the Treatment of Brain	Shiao Y. Woo
	Real-time Tumor-tracking Intensity-synchronized Radiotherapy	Hiroki Shirato
	IMRT for Prostate Cancer: Image Guidance and Hypofractionation	Alan Pollack
	Clinical results of radiation therapy for localized prostate cancer, and experimental data of molecular targeting for enhancement of radiosensitivity in prostate cancer cell lines	Tetsuo Akimoto
	Imaging of hypoxic cells	Yoshihiro Takai
October 3 (Fri.) Pelvis and Thorax
	Management of cancer of the prostate and dose escalation without increasing toxicity	Mack Roach III
	Genomic Analysis for Cervical Cancer after Radiotherapy	Yoko Harima
	Cytoprotection for management Lung Cancer	Ritsuko Komaki
	Genetic predictor of EGF receptor-targeted therapy for non-small cell lung cancer	Saburo Sone
	Current status of 3-D stereotactic radiotherapy for early lung cancer	Yasushi Nagata:
	The role of targeting therapy in breast cancer	Masahiro Hiraoka
	Molecular Targeting for Breast Cancer	Catherine C. Park
	Chemoradiation for esophageal cancer: Current status in Japan and future directions	Satoshi Ishikura
	Targeting RT with Concurrent CT for Cancer of the Esophagus	James D. Cox
	Current status of high dose rate brachytherapy for esophageal cancer	Yutaka Hirokawa
October 4 (Sat.) Integration of Targeted Cancer Therapy
	Integrating the Advances in Radiotherapy and Biological Imaging	C. Clifton Ling
	Potential molecular targets in radiation therapy	Norio Mitsuhashi
	Integration of Hypoxia Imaging in Cancer Treatment	K.S. Clifford Chao

Scientific Achievements
1) October 2 (Thu.) : Head and Neck including Brain
a) Ang: Molecular Predictor and Therapeutic Target in Head and Neck Carcinoma
Ang reported limitation of so-called chemoradiation and referred to the possibility of concurrent administration of molecular-targeted drug and radiation.
b) Nishimura: Improvement in Therapeutic Ratio for Head and Neck Cancers by Chemoradiotherapy and IMRT
Experience in concurrent chemoradiation for head and neck cancers using Docetaxel was reported. Improvement of therapeutic ratio for head and neck cancers using IMRT was also demonstrated.
c) Milas:C225 & radiotherapy; targeting treatment to EGFR-antibody in head & neck cancer
Sensitization effect of novel anti-EGFR antibody C225 on both chemotherapeutic agent and radiation for head and neck cancers with high EGFR expression was demonstrated.
d) Fuwa: Continuous superselective intraarterial chemotherapy combined with radiotherapy for head and neck cancer
The method and results of superselective intraarterial chemotherapy combined with radiotherapy for head and neck cancer was demonstrated. The advantage over systemic chemotherapy was discussed.
e) Lee: IMRT for Nasopharyngeal Tumors
Experience of IMRT for nasopharyngeal cancer was reported. Preservation of the function of salivary gland was demonstrated.
f) Woo: The use of Intensity Modulated Radiation Therapy in the Treatment of Brain
Reduction of late oto-toxicity in the treatment of medulloblastoma by using IMRT boost was reported.
g) Shirato: Real-time Tumor-tracking Intensity-synchronized Radiotherapy
Increase of therapeutic ration by combining Real-time Tumor-tracking system System and IMRT was reported. Its results in pelvic tumors and head and neck cancers was were also reported.
h) Pollack: IMRT for Prostate Cancer: Image Guidance and Hypofractionation
Current status and problem of hypofractionated radiation therapy for prostate cancer was reported.
i) Akimoto: Clinical results of radiation therapy for localized prostate cancer, and experimental data of molecular targeting for enhancement of radiosensitivity in prostate cancer cell lines
Current status of hypofractionated external beam radiation therapy followed by high dose rate brachytherapy for prostate cancer was reported. Radiosensitization effect of Hsp90 chaperone complex inhibitor, radicicol, was also reported
j) Takai: Imaging of hypoxic cells
Visualization of hypoxic cells by double-tracer autoradiography using [18F] labeled fluoroRP-170, 4-[N-methyl-14C] iodoantipyrine, and 2-[1-14C]-deoxy-D-glucose was reported.
2) October 3 (Fri.): Pelvis and Thorax
a) Roach: Management of cancer of the prostate and dose escalation without increasing toxicity
Reduction of the risk of impotence after radiation therapy for prostate cancer by reducing the dose to penile bulb was reported.
b) Harima: Genomic Analysis for Cervical Cancer after Radiotherapy
Prediction of radiosensitivity using cDNA microarray was reported. Both local control and survival was poor in Ku80 positive tumors.
c) Komaki: Cytoprotection for management Lung Cancer
Usefulness of radioprotector WR2721 in chemoradiation therapy for lung cancer was reported.
d) Sone: Genetic predictor of EGF receptor-targeted therapy for non-small cell lung cancer
Effect of organ-specific microenvironment in the development of metastases was analyzed using cDNA microarray. Prediction of the effect of EGFR-TKI on lung cancer was also explored using cDNA microarray.
e) Nagata: Current status of 3-D stereotactic radiotherapy for early lung cancer
The result of 3-dimensional stereotactic radiation therapy for early lung cancer was reported.
f) Hiraoka: Çshe role of targeting therapy in breast cancer
Physical targeting in breast conserving therapy was demonstrated. Gene therapy using hypoxia induced vector and suicide gene NTR was also demonstrated.
g) Park: Molecular Targeting for Breast Cancer
The effect of interaction between organ microenvironment and tumor cells on radiosensitivity was reported. Novel radiosensitization mechanism by inhibition of b1 integrine was proposed.
h) Ishikura: Chemoradiation for esophageal cancer: Current status in Japan and future directions
The result of chemoradiation therapy for esophageal cancer was reported. Special emphasis was made on the late toxicity in lung and heart.
i) Cox: Targeting RT with Concurrent CT for Cancer of the Esophagus
The optimization of tri-modality approach (Chemoradiation chemoradiation therapy and surgery) for esophageal cancer was discussed.
j) Hirokawa: Current status of high dose rate brachytherapy for esophageal cancer
Current status of high dose rate brachytherapy for esophageal cancer in Japan was reported. The importance of the dose per fraction to reduce the risk of late toxicity was demonstrated.
3) October 4 (Sat.) : Integration of Targeted Cancer Therapy
a) Ling: Integrating the Advances in Radiotherapy and Biological Imaging
The importance of treatment planning based on not only anatomic image but also functionl image was reported. The concept of “dose painting” was introduced.
b) Mitsuhashi: Potential molecular targets in radiation therapy
Potential molecular targets in intracellular signal transduction pathways (EGFRÅAHsp90-chaperone complexÅAand HDAC) were comprehensively reviewed.
c) Chao: Integration of Hypoxia Imaging in Cancer Treatment
Use of fused image of CU-ATSM PET and X-CT in the treatment planning of radiation therapy to selectively increase the dose to hypoxic area of the tumor was reported.

Other Seminar Activities
Reception (All the members participate.): October 2, 18:00 ~ Kyoto Park Hotel (JSPS sources of revenue)
Dinner party: October 4, 18:00~ Ran-tei (Other sources of revenue)

Comments and Opinions
We appreciate the financial support from JSPS which enabled us to perform this fruitful meeting.
The topic “Physical and biological targeting in radiation oncology” of this seminar was so timely and stimulating that participants from US want to continue the seminar of the same topic.



2. Screening Detected Lung Cancer, A New Clinical Entity: Diagnostic, Pathologic, and Therapeutic Issues and Approaches to Innovative Research
Period: from October 30 to November 2, 2003, 4 days
Site: The Asakusa View Hotel, Nishi-asakusa, Taito, Tokyo

Japanese Organizer
YOSHIDA, Junji
National Cancer Center Hospital East
Division of Thoracic Surgery
Attending Thoracic Surgeon

US Organizer
SAXMAN, Scott
National Cancer Institute
Cancer Therapy Evaluation Program
Senior Investigator


List of Japanese-side Participants
OHMATSU, Hironobu
Attending Physician
National Cancer Center Hospital East, Chiba

OHNO, Yoshiharu
Assistant Professor
Kobe University Graduate School of Medicine

ISHIKAWA, Yuichi
Associate Member
Cancer Institute, Japanese Foundation for Cancer Research

YATABE, Yasushi
Attending Thoracic Surgeon
Aichi Cancer Center Hospital

SUZUKI, Kenji
Senior Pathologist
National Cancer Center Hospital

SEKIDO, Yoshitaka
Assistant Professor
Nagoya University School of Medicine

NAGATA, Yasushi
Associate Professor
Graduate School of Medicine, Kyoto University

OKUNAKA, Tetsuya
Head and Professor
San'no Hospital, International University of Health and Welfare

SANO, Yoshifumi
Assistant
Okayama University Graduate School of Medicine and Dentistry

TAKAMI, Koji
Attending Thoracic Surgeon
Osaka Medical Center for Cancer and Cardiovascular Diseases

List of US-side Participants
Jonathan G. Goldin
Associate Professor
David Geffen School of Medicine at UCLA

Matthew Meyerson
Associate Professor
Dana-Farber Cancer Institute, Harvard Medical School

Robert D. Timmerman
Associate Professor
Indiana University School of Medicine

Fadlo Khuri
Associate Director
Winship Cancer Institute, Emory University School of Medicine

Scott Swanson
Chief
Mt Sinai Medical Center,

Itinerary and Topics
October 31 (Friday)
Presentations and discussions on diagnostic radiology, pathology, and molecular biology.
November 1 (Saturday)
Invited lecture on new drug approval system and clinical research grant support in Japan was given by Dr. FUJIWARA, Yasuhiro, Deputy Director, Clinical Trial Coordinating Office, National Cancer Center Hospital. Presentations and discussions on non-surgical intervention followed.
November 2 (Sunday)
Presentations and discussions on surgical intervention followed by lectures to provide perspectives on collaborative research across the Pacific by Dr. Rui-Ping Dong, Medical Director of Clinical Research/Oncology, AstraZeneca US and Dr. Scott Saxman, Senior Investigator, Cancer Therapy Evaluation Program, National Cancer Institute.
The agenda book is attached.

Scientific Achievements
The attendees exchanged cutting-edge information and discussed on:
l) Comparison of two lung cancer screening periods in Japan with or without helical CT
2) Randomized U.S. Iung cancer screening trial
3) New application of MR imaging for lung cancer
4) Pathologic characteristics of non-invasive carcinoma in the peripheral lung
5) Role of cellular lineage in the pulmonary adenocarcinoma
6) Prospective study of radiologic-pathologic correlation for lung cancer in Japan
7) Gene expression analysis and profiling of lung cancer and their relevance for developing novel therapeutic strategies
8) Alterations of protooncogenes and tumor suppressor genes in lung cancer
9) Novel radiotherapeutic approaches for stage I Iung cancer
10) Photodynamic therapy for peripheral type lung cancer
11) Radiofrequency ablation of lung cancer
12) Chemoprevention of early lung cancer
13) Minimally invasive surgical approaches for small lung cancers
14) Prospective study of operation methods for small sized lung cancers in Japan.

Three lectures provided perspectives on international collaboration:
New drug approval system and clinical research grant support in Japan by Dr. Fujiwara of the National Cancer Center Hospital
Global clinical study - the benefit and difficulty by Dr. Dong of AstraZeneca US
3) Organizational structure and conduct of cancer research sponsored by the Cancer Therapy Evaluation Program of the National Cancer Institute by Dr. Saxman of the National Cancer Institute

Collaboration ideas were presented on:
1) Definition on early peripheral lung cancers
2) Optimal treatment of "early" peripheral lung cancers
3) Natural history of ground-glass opacity lesions
4) Difference in lung cancer molecular/genetic characteristics across the Pacific
5) Difference in diagnostic/therapeutic practice across the Pacific
6) MAC (malignancy associated changes) cells in sputum and buccal smear

Other Seminar Activities (Reception, Excursion, other meetings)
October 30 (Thursday) 19:30-
Welcome reception.
October 31 (Friday) 14:00-
Afternoon bus excursion of the Tokyo metropolitan.

Comments and Opinions
The organizers and attendees are indebted to the JSPS and NCI for their generous support. Even more so after they allowed us to carry over the Seminar to the next fiscal year.
Dr. Scott Saxman, the US organizer added the following: All of the U.S. investigators expressed their appreciation for the meeting and all felt that the meeting was extremely successful in fostering the exchange of scientific information that clearly will impact on the design and collaborative efforts in both countries and hopefully between countries in this disease entity. This clearly was a well organized and extremely valuable conference. Dr. Yoshida is to be congratulated for leading this important effort. All attendees genuinely benefited and are grateful for the JSPS and NCI support.