RADIATION ONCOLOGY

The Department of Radiation Oncology at Fox Chase consists of three sections: clinical radiation oncology, radiation physics, and tumor biology and biophysics. The clinical radiation oncology section participates in several aspects of cancer treatment including clinical care, clinical research, and education.

A number of the departmental programs, including the prostate cancer program, the breast cancer program and the esophageal cancer program, continue to have international recognition and an international leadership role. In addition, clinical programs in lung cancers, head and neck cancers, and gastrointestinal cancers maintain national prominence and an important interdisciplinary leadership role. Translational research programs continue to be an extremely important component of our clinical care program.

The Patterns of Care Studies chaired by Dr. Hanks provide national benchmarks for radiation therapy in the management of several malignancies for which radiation therapy has played an important curative role over the last 20 years. These studies have established a national basis for improving cancer treatment by radiation and provide a basis for quality assurance in radiation oncology.

Over the period covered by this report, the Patterns of Care Studies have conducted national surveys of structure, process and outcome for patients treated in 1994 in the United States. The disease sites included are prostate cancer, cervical cancer, anal cancer, breast cancer, esophageal cancer, colorectal cancer and seminoma. These studies are designed to provide United States national averages for processes of care. A separate long term follow-up study has been conducted for patients accessed in the Patterns of Care Study in 1989 so that the first five year follow-up will be available for those disease sites originally surveyed in a process survey after treatment in 1989. A unique study has been completed in facilities treating 40% or more minority patients. Prostate cancer and cervical cancer patients have been surveyed for processes of care that are compared to the United States national sample; results from this study will be reported within the next year.

Our department continues to maintain a position in the top three for total case accrual and to demonstrate leadership in design, conduct and analysis of clinical trials in urologic cancer, gastrointestinal cancers, gynecologic cancers and lung cancer. The Radiation Therapy Oncology Group (RTOG) effort is an interdisciplinary effort on Fox Chase's behalf.

Prostate Cancer The prostate cancer program continues under the leadership of Dr. Hanks along with Drs. Horwitz and Pinover. During the period of this update, the following clinical investigations and research have been addressed. The prostate brachytherapy program has commenced. Permanent I-125 interstitial implants are one treatment option, along with three-dimensional (3D) conformal radiation therapy (3DCRT), for patients with early stage, clinically localized disease. For patients with locally advanced, non-metastatic disease, treatment on study with a combination of 3DCRT and two temporary interstitial high dose rate (HDR) prostate implants (FCCC 97-026) is now an option.

We continue to define the subsets of patients who benefit from increasing radiation doses using 3DCRT. We have published long-term results for patients with pre-treatment prostate-specific antigen (PSA) levels between 10 to 20 and >20 ng/ml (1). As the follow-up for the patients treated with 3DCRT has matured, we have demonstrated improvements in bNED (biochemical no evidence of disease) control with high (>7150 cGy) doses of radiation for patients with pre-treatment PSA levels <10 ng/ml (2), and with doses >7400 cGy for patients with pre-treatment PSA greater than 10 ng/ml. We also reported the bNED control results for patients with non-palpable PSA-detected prostate cancer, now the most common patient presentation due to screening (3).

The use of PSA has revolutionized the diagnosis, management, and assessment of treatment efficacy in prostate cancer. Multiple definitions of bNED control exist making direct comparisons of treatment modalities between institutions difficult. Recently, an American Society of Therapeutic Radiology and Oncology (ASTRO) committee developed a consensus definition. This year we reported the results of a study, which correlated this definition with the clinical outcome for patients with clinically localized prostate cancer, treated with external beam RT (4).

Other areas where we continue to further define the optimal radiation treatment for prostate cancer lies with the determination of pre-treatment prognostic factors. The impact of Gleason score, perineural invasion, and pre-treatment PSA level on bNED control were examined (5). The importance of target identification (the prostate in this case) increases with radiation dose. We continue to develop new ways to immobilize and identify the prostate for patients receiving high dose 3DCRT, and this year reported our results with daily computed tomography (CT) imaging (6). Collaborative efforts between our department and the Departments of Pathology and Radiology continued and several reports were published. We reported the results of a review of prostate biopsies and its impact on cost and treatment outcome (7). We also investigated the effect of palliative radiation for cranial nerve deficits in patients with metastatic prostate cancer. Finally, we reported an increase in the risk of late complications for patients with diabetes mellitus treated with external beam RT (8), the risk of developing metastases based on age (9), and the absence of risk of second malignancies following prostate irradiation (10).

We are currently investigating the effect of adjuvant hormones on rates of bNED control, a cost comparison of 3DCRT and conventional treatment, and the use of ultrasound to further define the location of the prostate during treatment.

Breast Cancer The breast cancer program in Radiation Oncology continues under the leadership of Dr. Fowble in conjunction with Drs. Freedman and Nicolaou. In 1998, our staff conducted many areas of important clinical research. The method of cancer detection and outcome of women treated by breast conserving surgery and radiation was evaluated based on whether or not they had used postmenopausal hormone replacement therapy (11). This study did not find an adverse effect of the hormone replacement therapy in detecting breast cancers early; these women, in fact, presented with smaller tumor sizes that were commonly detected by mammography. Although women who used replacement therapy had a minimal increase in breast recurrence, they had a statistically significant decrease in distant metastases and a small improvement in overall survival when compared with women without a history of hormone use. The interaction between margin status and adjuvant systemic therapy in women treated with breast-conserving surgery and radiation was also reported (12). Important findings in this study were that women with positive or close resection margins after a lumpectomy had significantly higher risks of recurrence in the breast after radiation when compared with women with clear negative margins. Adjuvant chemotherapy with or without tamoxifen appeared to delay, but not reduce, the appearance of breast recurrences, but only in those women with close or positive margins. Women who achieved negative resection margins with one or two breast-conserving surgeries had very low rates of breast recurrence (7% at 10 years after radiation). Additional research on the importance of resection margins for breast conservation with radiation was also reported and reviewed (13).

A study was conducted (by Dr. Nicolaou) on the patterns of regional lymph node recurrence in axillary node-positive women treated by breast conserving surgery and radiation. Among the important findings was the observation that African-American women were at a higher risk of developing a regional nodal recurrence than Caucasian women with similar stage breast cancer. For this reason, supraclavicular nodal irradiation is recommended if any axillary nodes are positive in an African American patient; this is in contrast to Caucasian women, in whom it is usually needed only if 4 or more nodes are positive. Furthermore, a radiation boost to the axilla was only of benefit in those patients with fewer than 6 lymph nodes dissected at surgery.

We also reported that bone scans are not necessary for most women with early stage breast cancer as part of their initial staging (14). Decreasing the use of bone scans for early stage disease could save considerable patient time and expense if implemented on a national level. Research examining the patterns of failure and prognosis of women who had recurrences after a mastectomy for initially noninvasive early stage breast cancer was also conducted (15). Results indicated that all of the recurrences were invasive cancers, the size of the recurrences on the chest wall was small showing they could be detected at an early stage, and that the interval to recurrence was long with a median detected 5 years after the initial mastectomy. Long term survival in these patients having an invasive recurrence after mastectomy was high with the combination of surgical excision, postoperative radiation, and adjuvant systemic therapy.

An important clinical advance in our breast program has been 3D field planning using CT scanning and virtual simulation for all women receiving postlumpectomy radiation. This technology is used to design the patient's electron boost fields used during the final 1.5 to 2 weeks of radiation. More accurate targeting of the entire biopsy cavity and scar within an intact breast is attainable with a radiation field as small as possible to spare the remaining breast tissue, chest wall, and lung. The CT simulation allows optimization of field parameters such as electron prescription depth, beam orientations and choice of treatment energies. The preliminary results of this research have been reported (16).

Several other findings were conducted and published in 1998, including: 1) a report that a close or positive margin after mastectomy was an indication for post-mastectomy radiation in some women (17), 2) a study showing that women with proliferative changes in the breast tissue outside of the main cancer did not increase the risk of recurrence after breast-conserving surgery and radiation (18), 3) an analysis of the percentages of heart and lung volumes in standard radiation fields used to treat breast cancer (19), and 4) work illustrating the potential for inadequate treatment of large breasted women when they are radiated in a prone rather than standard supine position (20).

In summary, the breast cancer program in Radiation Oncology conducted many areas of important clinical research and collaborative efforts with the Medical and Surgical Oncology groups at Fox Chase in 1998. These activities shared a common goal of addressing important clinical questions that arise in the management of our breast cancer patients. Our efforts this year brought some answers in areas of hormone replacement therapy and breast cancer, the optimal margins after breast-conserving surgery, the irradiation of regional lymph nodes in early stage breast cancer, and the optimal technique for irradiating the tumor bed after breast-conserving surgery.

The department is committed to training residents and fellows in radiation oncology for academic and clinical research positions so they may advance the frontiers of the field. The residency-training program at Fox Chase, currently under the direction of Dr. Pinover, was initiated in 1992 and represents the only Fox Chase-based residency program.

Nurses in the department are leaders in the national Quality of Life (QOL) studies. Clinical Nurse Specialist, D. Bruner, who is co-chair of the RTOG-QOL Committee, a member of the Gynecology Oncology Group QOL Committee, and chair of the ASTRO QOL committee, has developed QOL studies for prostate, bladder and gynecologic cancers. In-house research studies include gynecologic, rectal, and pelvic QOL protocols.

The Prostate Cancer Risk Assessment Program (PRAP) has been initiated in collaboration with the Population Science Division. The purpose of the program is to: 1) identify the relatives of prostate cancer patients who are at increased risk, 2) solicit their involvement in appropriate screening, and 3) study them from a genetic, behavioral, dietary and environmental exposure point to assess the relative roles of these parameters in the initiation of these cancers. Dr. Hanks is the program director and D. Bruner is the program coordinator.

1.   HANKS, G.E., HANLON, A.L., SCHULTHEISS, T.E., PINOVER, W.H., MOVSAS, B., EPSTEIN, B.E., HUNT, M.A. Dose escalation with 3D conformal treatment: Five year outcomes, treatment optimization and future directions. Int. J. Radiat. Oncol. Biol. Phys. 41(3):501-510, 1998.

2.   HORWITZ, E.M., VICINI, F.A., ZIAJA, E.L., DMUCHOWSKI, C.F., STROMBERG, J.S., MARTINEZ, A.A. The correlation between the ASTRO consensus panel definition of biochemical failure and clinical outcome for patients with prostate cancer treated with external beam irradiation. Int. J. Radiat. Oncol. Biol. Phys. 41:267-272, 1998.

3.   HORWITZ, E.M., HANLON, A.L., PINOVER, W.H., HANKS, G.E. The treatment of non-palpable PSA detected adenocarcinoma of the prostate with 3-dimensional conformal radiation therapy. Int. J. Radiat. Oncol. Biol. Phys. 41:519-523, 1998.

4.   HORWITZ, E.M., HANLON, A.L., HANKS, G.E. An update on the treatment of prostate cancer with external beam irradiation. The Prostate 37:195-206, 1998.

5.   ANDERSON, P.R., HANLON, A.L., PATCHEFSKY, A., AL-SALEEM, T., HANKS, G.E. Perineural invasion and Gleason 7-10 tumors predict increased failure in prostate cancer patients with pretreatment PSA <10 ng/ml treated with conformal external beam radiation therapy. Int. J. Radiat. Oncol. Biol. Phys. 41(5):1087-1092, 1998.

6.   LATTANZI, J.P., MCNEELEY, S.W., HANLON, A.L., DAS, I., SCHULTHEISS, T.E., HANKS, G.E. Daily CT localization for correcting portal errors in the treatment of prostate cancer. Int. J. Radiat. Oncol. Biol. Phys. 41(5):1079-1086, 1998.

7.   WURZER, J.C., AL-SALEEM, T.I., HANLON, A.L., FREEDMAN, G.M., PATCHEFSKY, A., HANKS, G.E. Histopathic review of prostate biopsies from patients referred to a comprehensive cancer center. Correlation of pathologic findings, analysis of cost, and impact on treatment. Cancer 83(4):753-759, 1998.

8.   HEROLD, D.M., HANLON, A.L., HANKS, G.E. Diabetes Mellitus: Predictor for late radiation morbidity. Int. J. Rad. Oncol. Biol. Phys. 43:475-479, 1999.

9.   HEROLD, D.M., HANLON, A.L., MOVSAS, B., HANKS, G.E. Age-related prostate cancer metastases. Urology 51(6):985-990, 1998.

10.   MOVSAS, B., HANLON, A.L., PINOVER, W., HANKS, G.E. Is there an increased risk of second primaries following prostate irradiation? Int. J. Radiat. Oncol. Biol. Phys. 41(2):251-255, 1998.

11.   FOWBLE, B., HANLON, A.L., FREEDMAN, G., PATCHEFSKY, A., KESSLER, H., NICOLAOU, N., HOFFMAN, J.P., SIGURDSON, E.R., BORAAS, M., GOLDSTEIN, L.J. Postmenopausal hormone replacement therapy (HRT): Effect on diagnosis and outcome in early stage invasive breast cancer treated with conservative surgery and radiation. Int. J. Radiat. Oncol. Biol. Phys. 42:180, 1998.

12.   FREEDMAN, G.M., FOWBLE, B., HANLON, A., FEIN, D., NICOLAOU, N., HOFFMAN, J., SIGURDSON, E., BORAAS, M., GOLDSTEIN, L. Patients with close or positive margins treated with conservative surgery and radiation have an increased risk of breast recurrence that is delayed by adjuvant systemic therapy. Int. J. Radiat. Oncol. Biol. Phys. 42: 126, 1998.

13.   FOWBLE, B. The significance of resection margin status in patients with early-stage invasive cancer treated with breast-conservation therapy. The Breast J. 4:126-131, 1998.

14.   MONTGOMERY R.C., FOWBLE B.L., GOLDSTEIN L.J., HOFFMAN J.P., SIGURDSON, E.R., MAY, D., HANLON, A., EISENBERG, B.L. Local recurrence after mastectomy for ductal carcinoma in situ: a recurrence with a good prognosis. The Breast J. (in press).

15.   HADLEY, D., FOWBLE, B., TOROSIAN, M.H. Evidence for selective use of bone scans in early stage breast cancer. Oncol. Rep. (in press).

16.   DAS, I., CHENG, E.C., WURZER, J.C., FREEDMAN, G., FOWBLE, B. Impact of CT simulation for radiation cone down treatment of breast cancer. Int. J. Radiat. Oncol. Biol. Phys. 42:244, 1998.

17.   Freedman, G.M., Fowble, B.L., Hanlon, A.L., Myint, M.A., Hoffman, J.P., Sigurdson, E.R., Eisenberg, B.L., Goldstein, L.J., Fein, D.A. A close or positive margin after mastectomy is not an indication for chest wall irradiation except in women aged fifty or younger. Int. J. Radiat. Oncol. Biol. Phys. 41:599-605, 1998.

18.   Fowble, B., Hanlon, A.L., Patchefsky, A., Freedman, G., Hoffman, J.P., Sigurdson, E.R., Goldstein, L.J. The presence of proliferative breast disease with atypia does not significantly influence outcome in early stage invasive breast cancer treated with conservative surgery and radiation Int. J. Radiat. Oncol. Biol. Phys. 42:105-115, 1998.

19.   Das, I.J., Cheng, E.C., Freedman, G., Fowble, B. Lung and Heart Dose Volume Analyses with CT Simulator in radiation treatment of breast cancer. Int. J. Radiat. Oncol. Biol. Phys. 41:599-605, 1998.

20.   Algan, Ö., Fowble, B., McNeeley, S., Fein, D. Use of the prone position in radiation treatment for women with early stage breast cancer. Int. J. Radiat. Oncol. Biol. Phys. 40:1137-1140, 1998.

AJANI, J.A., EISENBERG, B., EMANUEL, P., FUCHS, C., HAYMAN, J., HEITMILLER, R., KURTZ, R., LEVIN, B., MEROPOL, N., MINSKY, B., MOVSAS, B., NESBITT, J., ORRINGER, M., POEN, J., PUTNAM, J.B., SCHWARZ, R. NCCN practice guidelines for upper gastrointestinal carcinomas. Oncology 12(11A):179-223, 1998.

CHAPMAN, J., ENGELHARDT, E., STOBBE, C., SCHNEIDER, R., HANKS, G. Measuring hyPOXIA AND predicting tumor radioresistance with nuclear medicine assays. Radiother. Oncol. 46:229-237, 1998.

COIA, L., MINSKY, B., JOHN, M., HALLER, D., LANDRY, J., PISANSKY, T., WILLET, C.G., MAHON, I., OWEN, J., HANKS, G. Patterns of care study decision tree and management guidelines for esophageal cancer. Radiat. Med. 16:321-327, 1998.

FOWBLE, B. The significance of resection margin status in patients with early-stage invasive cancer treated with breast-conservation therapy. The Breast J. 4:126-131, 1998.

GREEN, G.A., HANLON, A.L., AL-SALEEM, T., HANKS G.E. A Gleason score of 7 predicts for a worse outcome for prostate carcinoma patients treated with radiotherapy. Cancer 83:971-976, 1998.

HADLEY, D., FOWBLE, B., TOROSIAN, M.H. Evidence for selective use of bone scans in early stage breast cancer. Oncol. Rep. (in press).

HALL, E., SCHIFF, P., HANKS, G., BRENNER, D., RUSSO, J., CHEN, J., SAWANT, S., PANDITA, T. A preliminary report: frequency of A-T heterozygotes among prostate cancer patients with severe late responses to radiation therapy. The Cancer J. From Sci. Am. 4:385-389, 1998.

HANKS, G.E., BUZYDLOWSKI, J., SAUSE, W.T., EMAMI, B., RUBIN, P., PARSONS, J.A., RUSSELL, A.H., BYHARDT, R.W., EARLE, J.D., PILEPICH, M.V. Ten year outcomes for pathologic node positive patients. Int. J. Rad. Oncol. Biol. Phys. 40(4):765-768, 1998.

HANKS, G.E. Strategies for improving the outcome of patients with poor prognosis prostate cancers. Acta Oncologica 37(1):5-9, 1998.

HANLON, A.L., MOORE, D.F., HANKS, G.E. Modeling post-radiation PSA level kinetics: Predictors of rising post-nadir slope suggest cure in men who remain biochemically free of prostate cancer. Cancer 83:130-134, 1998.

HANLON, A.L., HANKS, G.E. Patterns of inheritance and outcome in prostate cancer. Urology 52:735-738, 1998.

KATZ, A., HANLON, A.L., LANCIANO, R.M., HOFFMAN, J.P., COIA, L.R. Prognostic value of CA 19-9 levels in patients with carcinoma of the pancreas treated with radiotherapy. Int. J. Radiat. Oncol. Biol. Phys. 41:393-396, 1998.

MINSKY, B.D., COIA, L., HALLER, D., HOFFMAN, J., JOHN, M., LANDRY, J., PISANSKY, T., WILLETT, C., MAHON, I., OWEN, J., HANKS, G. Treatment systems guidelines for primary rectal cancer from the 1996 Patterns of Care Study. Int. J. Rad. Oncol. Biol. Phys. 41:21-27, 1998.

MOVSAS, B., BARROWS, M.C., STEINBERG, S.M., MIDDLETON, L.P., OKUNIEFF, P., JAFFE, E.S., EPSTEIN, A.H. Response during radiotherapy may be associated with outcome in mediastinal Hodgkin's disease. Radiat. Oncol. Invest. 6:216-225, 1998.

MOVSAS, B., HANLON, A.L., LANCIANO, R., SCHER, R.M., WEINER, L.M., SIGURDSON, E.R., HOFFMAN, J.P., EISENBERG, B.L., COOPER, H.S., PROVINS, S., COIA, L.R. Phase I dose escalating trial of hyperfractionated pre-operative chemoradiation for locally advanced rectal cancer. Int. J. Radiat. Oncol. Biol. Phys. 42(1):43-50, 1998.

MOVSAS, B., TERUYA-FELDSTEIN, J., SMITH, J., GLATSTEIN, E., EPSTEIN, A. Primary cardiac sarcoma: A novel treatment approach using hyperfractionated radiotherapy and 5'-Iododeoxyuridine. Chest 114(2): 648-652, 1998.

RECHT, A., BARTELINK, H., FOURQUET, A., FOWBLE, B., HARRIS, J.R., KURTZ, J., MCCORMICK, B., OLIVOTTO, I.A., RUTQVIST, L., SOLIN, L.J., YARNOLD, J. Postmastectomy radiotherapy: Questions for the Twenty-First Century. J. Clin. Oncol. 16:2886-2889, 1998.

TESHIMA, T., ABE, M., IKEDA, H., HANKS, G.E., OWEN, J.B., HIRAOKA, M., HIOKAWA, Y., OGUCHI, M., NISHIO, M., YAMASHITA, T., NIIBE, H., MASUDA, K., WATANABE, S., INOUE, T. Patterns of Care study of radiation therapy for esophageal cancer in Japan: influence of the stratification of institution on the process. Jpn. J. Clin. Oncol. 28(5):308-313, 1998.

HORWITZ, E.M., HANLON, A.L., HANKS, G.E. An update on the treatment of prostate cancer with external beam irradiation. Prostate 37:195-206, 1998.

SIEGELMANN-DANIELI, N., HANLON, A., RIDGE, J.A., PADMORE, R., FEIN, D.A., LANGER, C.J. Oral tongue cancer in patients less than 45 years old: institutional experience and comparison with older patients. J. Clin. Oncol. 16(2):745-753, 1998.

STROMBERG, J.S., MARTINEZ, A.A., HORWITZ, E.M., GUSTAFSON, G.S., GONZALEZ, J., SPENCER, W., BRABBINS, D.S., DMUCHOWSKI, C.F., HOLLANDER, J., VICINI, F.A. Conformal high dose rate Ir-192 boost brachytherapy in locally advanced prostate cancer: Superior prostate specific antigen response compared to external beam treatment. The Cancer J. from Sci. Am. 3:346-352, 1997.

TESHIMA, T., HANK, G.E., HANLON, A.L., PETER, R.S., SCHULTHEISS, T.E. Rectal bleeding after conformal 3D treatment of prostate cancer: time to occurrence, response to treatment and duration of morbidity. Int. J. Radiat. Oncol. Biol. Phys. 39(1):77-83, 1997.

VICTOR, S.J., BROWN, D.M., HORWITZ, E.M., MARTINEZ, A.A., KINI, V.R., PETTINGA, J.E., SHAHEEN, K.W., CHEN, P.Y., VICINI, F.A. Treatment outcome with radiation therapy after breast augmentation or reconstruction in primary breast cancer. Cancer 82:1303-1309, 1998.

^a   A. Katz: Present address--Division of Radiation Oncology, The University of Texas, M.D. Anderson Cancer Center, Houston, TX 77030

Illustrations or unpublished data in these reports should not be used without permission of the author.

Fox Chase Cancer Center

Scientific Report 1998