LUNG CANCER PROGRAM AREA REPORT
September 1977 to October 1978

Program Coordinators: Dr. Yuichi Yamamura
Dr. Oleg Selawry


Summary of Activities
During this reporting period, activities of the Lung Cancer Program Area were as follows:

MEETINGS, SEMINARS, AND CONFERENCES
The Fourth Joint Seminar on Lung Cancer was held in the East-West Center, Honolulu. Hawaii, on February 2 and 3, 1978, on the subject of Multidisciplinary Treatment of Lung Cancer. This conference was attended by seven American and six Japanese participants and included 15 presenrations with six discussion periods covering progress in :
1. Morphology.
Dr. Raymond Yesner. Chair-man of the WHO Committee, and Dr.Yukio Shimosato, a member of the WHO Committee, presented the WHO Second Edition of Morphology of Pulmonary Neoplasms.
2. Immunotherapy.
Dr. Yuichi Yamamura presented the newest advances in chemistry and clinical application of cell-wall skeletons: Dr. Kenneth Ramming presented current data on surgical adjuvant intratumorous injection of BCG: and Dr. Ramming of the U.S. and Dr. Mitsuo Ohta of Japan presented the present status of immunotherapy in the United States.
3. Multidisciplinary Treatment of Small Cell Carcinoma.
Dr. Shoji Hattori presented multidisciplinary treatment in Japan, including surgery: Dr. Ralph Johnson presented experiences with aggressive radiotherapy and chemotherapy: and Dr. Lawrence Broder presented treatment with non-cross resistant drug combinations.
4. Multidisciplinary Treatment of Non-small Cell Cancer.
Summaries for Japan were presented by Dr. Shoji Hattori and for the U.S. by Dr. Oleg Selawry, stressing the consistent 60 percent response rates for chemotherapy of adenocarcinoma.
5. Adjuvant Surgery.
Drs. Clifton Mountain and Keiichi Suemasu presented summaries.
6. Cell Kinetics and Marker Substances.
The impact of cell kinetics and marker substances on planning and monitoring of therapeutic studies were presented by Drs. Marc Strauss and Lawrence Broder.
The presentations at this seminar reflected considerable mutual progress in all areas of the Lung Cancer Program Area. The agenda of this meeting follows this report.

EXCHANGE OF SCIENTISTS
Two American scientists, Dr. Clifton Mountain and Dr. Oleg Selawry, made highly rewarding visits to Japan during this reporting period. From June 26 to July 7, they visited the National Cancer Center Hospital (Dr. Ishikawa): the Tokyo Medical College (Dr. Hayata): Aichi Medical Center, Nagoya (Dr. Nishimura): Osaka Medical Center (Dr. Yamamura): the Center for Adult Diseases in Osaka (Dr. Hattori); and the Kyushu Cancer Center in Fukuoka (Dr. Ohta). They learned about progress in fiberoptic bronchoscopy from Dr. Ikeda at the Cancer Center Hospital and from Dr. Oho at the Tokyo Medical College; new needles for trans-thoracic biopsy (Dr. Oho); chemistry and experimental data on cell-wall skeletons of various origins (Dr. Yamamura and co-worker); and clinical experience with these cell-wall skeletons (Drs. Hayata, Yamamura, Hattori, Ohta, and co-worker).
During their very stimulating meetings with these Japanese scientists, Dr. Mountain had the opportunity to present his own data on surgical staging and surgical adjuvant treatment, and Dr. Selawry presented data on chemotherapy. Two Japanese scientists visited and studied in the United States as part of the exchange program of the Lung Cancer Program Area. Dr. Nagahiro Saijo of the National Cancer Center Hospital in Tokyo, studied at the M.D. Anderson Hospital in Houston, Texas; visited the Comprehensive Cancer Center for the State of Florida (Miami) and the National Cancer Institute (NCI) in Bethesda, Maryland: and participated in the Annual Meeting of ASCO/AACR in Washington, D.C. These activities took place from March to July 1978.
Dr. Ryuhei Tateishi, of the Department of Pathology, Center for Adult Diseases (Osaka), visited the United States from June 28 to July 29, 1978. His activities included visits to the New Haven Veterans Hospital: the Memorial Sloan-Kettering Cancer Center: the Washington, D.C., Veterans Administration Hospital; and the Mayo Clinic.

FIVE-YEAR SUMMARY REPORT
The following activities summarize the accomplishments of the Lung Cancer Program Area over the past five years:
1. Staging.
Drs. Mountain and Ishikawa advanced fully compatible and very similar staging systems for bronchogenic carcinoma. These staging systems are generally and widely accepted as the official staging systems in both countries.
2. Morphology.
Drs. Yesner. Shimosato. Melamed. Matthews, and Hattori reached full agreement on morphologic classification by cell type and ascertained congruence of interpretation by mutual slide reviews. Dr. Selawry had the opportunity to recommend representatives of both countries to the morphology committee of WHO (Dr. Sobin) for an update of the WHO Classification of Lung Cancer. Thus, Dr Yesner was invited as chairman of the WHO Committee and Dr. Shimosato as Committee Member, leading to the integration of their mutual work into the updated WHO publication Morphology of Pulmonary Neoplasms (Second Edition). This classification has found worldwide acceptance.
3. Early Diagnosis. (Drs. Frost, Sanderson. Fontana, Beattie, Ikeda, and Oho).
The Japanese investigators developed fiberoptic bronchoscopy and trained U.S. investigators in the use of these instruments for early diagnosis of cytology-positive, chestfilm negative cancer. The U.S. investigators, in turn, tested the new methodology in a major NCI-supported field trial (Dr. Berlin) and shared their results with their colleagues in Japan.
4. Therapy with Emphasis on Multidisciplinary Treatment. (Drs. Selawry and Yamamura).
U.S. investigators advanced the methodology of comparative clinical trials and the logic of drug development (Phase I to III Trials), now increasingly accepted in Japan. Japanese investigators defined the chemical structures of cell-wall skeletons and modified them, leading to reproducible and improved immunotherapeutic agents. Both countries contributed greatly to the development of antineoplastic drugs (discussed elsewhere). Ex-change contributed to impressive initial results in adjuvant immunotherapy and to substantial increases in response rate (including complete tumor regression in 40 to 60 percent of small-cell carcinoma) and longevity, notably in patients with small-cell and adenocarcinoma.
5. The U.S. Co-Chairman, Dr. Selawry, was elected the first non-Japanese honorary member of the Japan Lung Cancer Society.
6. Dr. Yamamura is a frequent participant in conferences and workshops in the U.S. on immunotherapy of lung cancer. Cell-wall skeletons from BCG and Nocardia rubra find increasing interest in laboratories and clinical studies in the United States.

Future Problems and Developments
Efforts over the last five years were mainly directed at better cure rates and more effective palliation of lung cancer. On the basis of this work, we are now prepared to extend our joint program toward prevention.
Agreement on diagnosis by cell type will permit the mapping of lung cancer incidence by cell type in order to focus on etiologic factors, which commonly express themselves in a relative increase of squamous and small-cell carcinoma, respectively. This might aid in cancer prevention by decreased exposure to carcinogens and co-carcinogens.
An increasing number of anticarcinogenic principles are successfully advanced against carcinogen-incuded respiratory cancer in animals. These include among others, analogues of retinoic acid (Bollag, Nettesheim, Sporn) and cell-wall skeletons of BCG and Norcardia rubra. Phase I studies and preliminary Phase II data on refined acid analogues are in progress.
Thus, controlled clinical trials in persons at high risk are in sight. If successful, they might represent the single most successful application of currently available methodology toward a decrease of lung cancer incidence and mortality.
The Fifth Joint Meeting of the Lung Cancer Program Area held in Miami, Florida, in February 1979, reflects this transition, focusing on squamous cell carcinoma and moving from treatment to chemoprevention and immunoprevention.




FOURTH JOINT SEMINAR ON LUNG CANCER
East-West Center
Honolulu, Hawaii
February 2 and 3, 1978

AGENDA
Thursday, February 2
9:00 a.m. Introductory Remarks Dr. Selawry and Dr. Yamamura
9: 10 a.m. Session I:
Progress in Morphology: The Updated WHO Classification of Lung Cancer, With Special Reference to the Morphologic Subtypes of Small-Cell and Large-Cell Carcinoma
9:30 a.m. WHO Committee for the Morphologic Classification of Lung Cancer Dr. Yesner-Chairman
9:50 a.m. WHO Committee for the Morphologic Classification of Lung Cancer Dr. Shimosato-Member
10:10 a.m. Discussion
10:25 a.m. COFFEE BREAK
10:40 a.m. Session II:
Advances in Immunotherapy of Lung Cancer Moderators: Dr. Yesner and Dr. Hayata
Immunotherapy of Carcinomatous Pleuritis with BCG Cell-Wall Skeleton Dr. Yamamura
11:10 a.m. The Present State of Immunotherapy of Lung Cancer in the U.S.A. Intratumoral Injection of Immunostimulants Dr. Ramming
11:30 a.m. Immunotherapy and Surgery of Lung Cancer Dr. Ohta
11:50 a.m. Discussion
12:05 p.m. LUNCH
Session III:
Progress in the Treatment of Small Cell Carcinoma Moderators: Dr. Suemasu and Dr. Strauss
2: 15 p.m. Non-Cross Resistant Drug Combinations Rationale and Current Experience Dr. Broder
2:35 p.m. Multidisciplinary Treatment Dr. Hattori
2:55 p.m. Considerations for Optimal Combination of Chemotherapy and Radiotherapy Dr. Ralph Johnson
3:15 p.m. Discussion
3:30 p.m. COFFEE BREAK
Session VI:
Treatment of Non-Small Cell Lung Cancer Moderators: Dr. Broder and Dr. Hattori
3:45 p.m. Multidisciplinary Treatment Dr. Hayata
4:05 p.m. Progress in Chemotherapy Dr. Selawry
4:25 p.m. Discussion
Evening: Reception for the Japanese Delegation

Friday, February 3
Session V:
Indications for Surgery in Advanced Lung Cancer Moderators: Dr. Ohta and Dr. Ramming
9:00 a.m. Dr. Mountain
9:20 a.m. Dr. Suemasu
9:40 a.m. Discussion
9:55 a.m. COFFEE BREAK
Session Vl:
Cell Kinetics and Marker Substances. Their Role for Planning and Monitoring of Therapeutic Studies Moderators: Dr. Yamamura and Dr. Ralph Johnson
10:10 a.m. Clinical Trials based on Cell Kinetics of Lung Cancer Dr. Strauss
10:30 a.m. Marker Substances in Lung Cancer: Incidence and Correlation with Clinical Course Dr. Broder
10:50 a.m. Discussion
Session VII:
Business Meeting-General Discussion and Future Plans Moderators: Dr. Selawry and Dr. Yamamura
12:00 noon Adjourn