Joint Center For Radiation Therapy Research Articles

First person profile: C. Norman Coleman, MD: A leading radiation and medical oncologist, Dr. Coleman has worked to improve cancer prevention, treatment, and quality of life on a global level.

First person profile: C. Norman Coleman, MD: A leading radiation and medical oncologist, Dr. Coleman has worked to improve cancer prevention, treatment, and quality of life on a global level.

When should proton radiation therapy be used to treat brain tumors?

Jay S Loeffler, MD, FACR, FASTRO, is an honors graduate of both Williams College (MA, USA) and Brown University School of Medicine (RI, USA). Loeffler completed his radiation oncology training at the Harvard Joint Center for Radiation Therapy, where he served as Chief Resident in 1985–1986, after completing a year of postdoctoral fellowship at the Harvard School of Public Health Radiobiology Laboratory with Jack Little. Since 1986 he has served on the faculty at Harvard Medical School (MA, USA), initially at the Brigham and Women’s Hospital (MA, USA) and Dana-Farber Cancer Institute (MA, USA). He also served as Director of the Brain Tumor Center at Brigham and Women’s Hospital, Dana-Farber Cancer Institute and Children’s Hospital from 1988 to 1996. He was recruited to the Massachusetts General Hospital (MA, USA) in 1996 as Director of the Northeast Proton Therapy Center. He served as the Andreas Soriano Professor and is currently the Herman and Joan Suit Professor of Radiation Oncology, Harvard Medical School and Chairman of the Department of Radiation Oncology since 2000. Loeffler is an authority on the treatment of benign and malignant brain tumors. He is an author of over 210 peer-reviewed publications, 180 book chapters and review articles, and co-editor of nine textbooks in the fields of radiation oncology and neuro-oncology. He has served as the principal investigator on a large program project grant from the National Cancer Institute concerning proton therapy. He has served on numerous journal editorial boards in the field of oncology. Loeffler is a Fellow of the American College of Radiology and the American Society of Radiation Oncology and is a Member of the Institute of Medicine of the National Academy of Sciences.

Unique management considerations for rectal cancer and colon cancer

Bruce D Minsky recently joined the Department of Radiation Oncology at the MD Anderson Cancer Center in Houston (TX, USA) as a Professor and Director of Clinical Research. Dr Minsky received his medical degree from the University of Massachusetts (USA). He completed an internship at New England Deaconess Hospital (MA, USA), and a residency in radiation therapy at Harvard Joint Center for Radiation Therapy (MA, USA). He spent 20 years in New York at the Memorial Sloan Kettering Cancer Center and was the Vice Chairman of Radiation Oncology and a Professor of Radiation Oncology in Medicine at Cornell University. From 2007 to 2012 he was a Professor of Radiation and Cellular Oncology and Associate Dean in the Biological Sciences Division at the University of Chicago (IL, USA). In 2004, Dr Minsky received a medical degree honoris causa from Friedrich Alexander University, Erlangen, Germany in recognition for his work in gastrointestinal cancers. Dr Minsky is an editorial board member of several journals and has served on the board of directors of the American Society of Clinical Oncology and the American Society for Therapeutic Radiology and Oncology Board of Directors.

Breastfeeding in survivors of Hodgkin lymphoma treated with chest radiotherapy

Female survivors of therapeutic chest radiation often question whether they will have difficulty with breast feeding, given their prior exposure to breast radiation. In the current study, the rates of successful breastfeeding in long-term survivors who received chest radiotherapy (CXRT) as a treatment for Hodgkin lymphoma (HL) were examined. A survey study of survivors of HL who were treated at the Joint Center for Radiation Therapy in Boston from 1969 through 1996 was performed. Patients were queried about childbearing and breastfeeding. The authors analyzed self-reported breastfeeding success in women who reported live births after CXRT and compared them with a sibling control group. Overall, 83 female survivors of HL who were treated with CXRT reported at least 1 birth after treatment. There were a total of 141 post-HL pregnancies resulting in births. In these women, the median age at the time of the HL diagnosis was 23 years (range, 14-40 years) and the median radiation dose was 41 grays (Gy) (range, 27-46 Gy). For survivors, 57 of the 94 (61%) breastfeeding attempts were successful, whereas within the control group, 74 of the 94 (79%) attempts were successful (P = .044). Accounting for maternal age at first birth and birth era, multivariable analysis suggested that HL survivors treated with CXRT may be less likely to breastfeed successfully than their siblings (odds ratio, 0.42; 95% confidence interval, 0.2-1.0 [P = .06]). The majority of female HL survivors who were treated with CXRT report being able to breastfeed successfully. However, the results of the current study indicate a trend toward less successful breastfeeding in survivors as a previously unreported late effect of radiation.

What Is the Appropriate Systemic Chemotherapy for Lymphocyte-Predominant Hodgkin's Lymphoma?

TO THEEDITOR: The optimal systemic therapy for lymphocytepredominant Hodgkin’s lymphoma (LPHL) is uncertain. It is known to be a rare variant with distinct morphologic and immunophenotypic differences compared to classic HL. The distinct B-cell immunophenotype, low-grade clinical biology, and lymph node usually not in a distribution more typical of classic HL questions as to the biology and appropriate chemotherapy. 1 The majority (approximately 80%) of patients present with localized disease. There have been no series of specific chemotherapy regimens published for those patients requiring systemic chemotherapy, and the question of regimen remains unanswered. We attempted to combined the systemic chemotherapy data in previously untreated patients with LPHL from two published Cancer and Leukemia Group B trials (8251 and 8952) 2,3 consisting of only 17 of a total 1,213 patients and published trials of the Dana-Farber Cancer Institute and Joint Center for Radiation Therapy 4,5 (20 of 127 patients) to gain some estimate of the effectiveness of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) or etoposide, vinblastine, and doxorubicin as compared to an alkylating agent-containing regimen, nitrogen mustard, vincristine, procarbazine, and prednisone (MOPP) or MOPP-ABVD hybrid. It is now known that the immunophenotypic features of CD20 allow for rituximab to be effective as an antitumor agent in patients relapsing from radiation therapy. 6 However, the mentioned trials preceded the

Radiosurgery for Intracranial Malignancies.

Radiosurgery was historically designed as a technology to be used for the treatment of functional disorders, benign tumors, and vascular malformations. In the last 5 years, malignant lesions have become an increasingly common target for the radiosurgeon. In fact, by 1994 the most common disease treated with radiosurgery in the United States was metastatic disease. Published data suggest that radiosurgery offers excellent local control for intracranial metastatic lesions regardless of location or histology with the majority of patients demonstrating an improved quality of life. Recent information from the Joint Center for Radiation Therapy suggests that radiosurgery compares favorably with interstitial brachytherapy for both recurrent as well as in newly diagnosed patients with malignant gliomas in terms of improved survival and the need of surgery and steroid support for symptomatic radiation changes. Prospective studies (Phase I through III) are ongoing to determine the ultimate role of radiosurgery in the management of patients with newly diagnosed and recurrent malignant gliomas, recurrent pediatric brain tumors disease, and patients with single or multiple intracranial metastases.

Cosmetic outcome and incidence of infection with the mammosite breast brachytherapy applicator

We present our results regarding the cosmetic outcome achieved and the rate of infection using the MammoSite breast brachytherapy applicator to treat patients with partial breast irradiation. In addition, factors associated with cosmetic outcome and infection are analyzed. The study population consisted of 30 patients with early stage breast cancer treated using the MammoSite device from October 28, 2002 to February 13, 2004. Treatment was delivered in 10 fractions of 3.4 Gy per fraction, b.i.d., with a minimum of 6 hours between daily fractions. Cosmetic outcome was assessed on a four-point scale using the scoring system developed at the Joint Center for Radiation Therapy. Cosmetic outcome was analyzed for its association with the following parameters: volume of the balloon, balloon-to-skin distance, maximal skin point dose per fraction, V100 (percent of volume that received 100% of the prescription dose), V150 (percent of volume that received 150% of the prescription dose) and V200 (percent of volume that received 200% of the prescription dose). The occurrence of infection at the time of treatment and during follow up was also recorded. The incidence of infection was analyzed for its association with track length (TL) (length of catheter located beneath the skin of the patient’s breast) and the use of chemotherapy. At a median follow up of 13 months (range 1 to 16), 53.3% of the patients (16/30) were reported to have an excellent cosmetic outcome, 40.0% (12/30) had a good cosmetic outcome, 3.3% (1/30) had a fair cosmetic outcome, and 3.3% (1/30) had a poor cosmetic outcome. Excellent cosmetic outcome was associated with a greater mean balloon-to-skin distance compared to those who achieved a good cosmetic outcome (1.46 cm vs. 1.19 cm). However, this did not reach statistical significance (p = .164). Sixty eight percent of patients with a skin distance greater than 0.7 cm had an excellent cosmetic outcome vs. 22% of patients with a skin distance less than 0.7 cm. The mean V100, V150, and V200 of those in the excellent cosmetic outcome group were 92.1%, 34.5%, and 7.6% vs. 93.0%, 34.7% and 7.6% in the good cosmetic outcome group (p = .642, .926, and .853), The mean balloon volumes were 47.7 cm3 and 56.9 cm3 respectively (p = .063) in the excellent and good outcome groups. The mean maximal skin doses per fraction in the excellent and good outcome groups were 354.8 cGy vs. 422.3 cGy (p = .286). Infection occurred in 13.3% of the patients (4/30). Systemic chemotherapy was used in 25% of the patients (1/4) who developed an infection and in 30.8% of the patients (8/26) who did not develop an infection. The mean TL of those patients who developed an infection was 8.50 cm vs. 8.16 cm (p = .625) in those patients who did not develop an infection. An excellent or good cosmetic outcome was achieved in 93.3% of patients treated with the MammoSite breast brachytherapy applicator. Excellent cosmetic outcome was associated with a greater balloon-to-skin distance, lower maximal skin dose per fraction, and smaller mean balloon volume, however the results did not reach statistical significance. Infection occurred in 13.3% of patients and was not associated with TL or systemic chemotherapy use.

Failure pattern implications following external beam irradiation of prostate cancer: long-term follow-up and indications of cure. Alexandra L. Hanlon, Ph.D.,a,b Gerald E. Hanks, M.D.,b Departments of aRadiation Oncology and bBiostatistics, Fox Chase Cancer Center, Philadelphia, PA, USA.Clinical utility of the percentage of positive prostate biopsies in defining biochemical outcome after radical prostatectomy for patients with clinically localized prostate cancer. Anthony

Failure pattern implications following external beam irradiation of prostate cancer: long-term follow-up and indications of cure. Alexandra L. Hanlon, Ph.D.,a,b Gerald E. Hanks, M.D.,b Departments of aRadiation Oncology and bBiostatistics, Fox Chase Cancer Center, Philadelphia, PA, USA.Clinical utility of the percentage of positive prostate biopsies in defining biochemical outcome after radical prostatectomy for patients with clinically localized prostate cancer. Anthony

The Harvard Joint Center for Radiation Therapy, 1968–1999: a unique concept and its relationship to the prevailing times in academic medicine

Purpose: Institutional structure, function, and philosophy reflect the organizational needs, and tend to mirror societal values of the times. For many years, the field of radiation oncology had among its major academic centers, an organization that served as a model for collaboration among health care institutions in an effort to serve the common good of its patients, hospitals, professional colleagues, and community. For over three decades, the Joint Center for Radiation Therapy (JCRT) was a leader in developing new organizational approaches for academic and clinical radiation oncology through the philosophy of collaboration in patient care, education, and research. Methods and Results: In tracing the development and changes in organizational philosophy and structure of the JCRT, one can see the impact on academic oncology and cancer care through the emergence of both radiation and medical oncology as independent subspecialties, the importance of the National Cancer Act of 1971 accompanied by the growth of the NIH research and training programs and, more recently, the effect of the changing attitudes and approaches of hospitals, academicians, practitioners, and policy makers to health care delivery, structures, and cooperation. Conclusion: Lessons learned from the 31-year history of the JCRT may help provide organizational insight useful in guiding academic oncology and academic medical centers through periods of change.

The relation between the presence and extent of lobular carcinoma in situ and the risk of local recurrence for patients with infiltrating carcinoma of the breast treated with conservative surgery and radiation therapy.

When found in an otherwise benign biopsy, lobular carcinoma in situ (LCIS) has been associated with an increased risk of development of a subsequent invasive breast carcinoma. However, the association between LCIS and the risk of subsequent local recurrence in patients with infiltrating carcinoma treated with conservative surgery and radiation therapy has received relatively little attention. Between 1968 and 1986, 1625 patients with clinical Stage I-II invasive breast carcinoma were treated at the Joint Center for Radiation Therapy at Harvard Medical School with breast-conserving surgery (CS) and radiation therapy (RT) to a total dose to the primary site of > or =60 grays. Analysis was limited to 1181 patients with infiltrating ductal carcinoma, infiltrating lobular carcinoma, or infiltrating carcinoma with mixed ductal and lobular features who, on review of their histologic slides, had sufficient normal tissue adjacent to the tumor to evaluate for the presence of LCIS and also had a minimum potential follow-up time of 8 years. The median follow-up time was 161 months. One hundred thirty-seven patients (12%) had LCIS either within the tumor or in the macroscopically normal adjacent tissue. The 8-year crude risk of recurrence was not significantly increased for patients with LCIS associated with invasive ductal, invasive lobular, or mixed ductal and lobular carcinoma. Among the 119 patients with associated LCIS adjacent to the tumor, the 8-year rate of local recurrence was 13%, compared with 12% for the 1062 patients without associated LCIS. For the 70 patients with moderate or marked LCIS adjacent to the tumor, the 8-year rate of local recurrence was 13%. The extent of LCIS did not affect the risk of recurrence. The risks of contralateral disease and of distant failure were similarly not affected by the presence or extent of LCIS. Breast-conserving therapy involving limited surgery and radiation therapy is an appropriate method of treating patients with invasive breast carcinoma with or without associated LCIS. Neither the presence nor the extent of LCIS should influence management decisions regarding patients with invasive breast carcinoma. [See editorial counterpoint and reply to counterpoint on pages 978-81 and 982-3, this issue.]

Postprostatectomy External Beam Irradiation

Background: A significant proportion of patients will be found to have extracapsular disease and/or detectable prostate specific antigen (PSA) values after radical prostatectomy. The role of postoperative radiotherapy to the prostatic tumor bed remains controversial. Methods: Ninety patients were treated at the Joint Center for Radiation Therapy after radical prostatectomy. The medium dose to prostatic fossa was 64.0 Gy. Medium follow‐up was 28.9 months (from time of prostatectomy). Failure after radiotherapy is defined as a persistently detectable PSA level or the development of a detectable PSA level after radiotherapy. None of the patients received androgen ablative therapy until documented postradiotherapy failure. Presurgical PSA levels, Gleason score, pathological findings at surgery, and preradiotherapy PSA levels were analyzed as predictors of PSA failure. Results: A presurgical PSA of >20.0 ng/ml is associated with PSA failure after radiotherapy (p = 0.0239). Preoperative Gleason score, PSA at time of radiotherapy or pathological findings at surgery do not predict for subsequent PSA failure. Conclusion: Postprostatectomy radiotherapy to the prostatic fossa is unlikely to provide long‐term PSA‐defined, disease‐free survival for patients who undergo prostatectomy with a presurgical PSA of >20 ng/ml. Regardless of findings at surgery, these patients have a high rate of developing PSA failure.

Correlation of tumor size and axillary lymph node involvement with prognosis in patients with T1 breast carcinoma

The prognosis of patients with T1 breast carcinoma remains controversial. Some studies have shown a low risk of lymph node metastasis and distant failure whereas others have not, possibly due to differences in the definition of tumor size. In this study, the authors assessed the relation between macroscopic tumor size, microscopic invasive tumor size, axillary lymph node involvement, and prognosis in a group of patients with clinically lymph node negative disease. Between 1968 and 1986, 1865 women with American Joint Committee on Cancer clinical Stage I or II infiltrating carcinoma of the breast were treated at the Joint Center for Radiation Therapy with conservative surgery and radiation therapy. The study population was limited to 118 patients with clinically negative axillary lymph nodes for whom the macroscopic pathologic tumor size was identified unambiguously as being < or = 2.0 cm, who underwent an axillary lymph node dissection with at least 6 lymph nodes sampled, and for whom the microscopic size of the invasive component could be determined. The median follow-up time for surviving patients was 134 months (range, 90-208 months). No patients with pathologically negative axillary lymph nodes received systemic therapy. Macroscopic and microscopic tumor sizes differed by > 5 mm in 17 patients (14%), by 3-5 mm in 24 patients (20%), and by < or = 2 mm in 77 patients (65%). The macroscopic tumor size was smaller than the microscopic size in 37 patients (31%), larger in 55 patients (47%), and equal in 26 patients (22%). Pathologic axillary lymph node involvement was present in 21% of all patients. The risk of lymph node involvement was not significantly different for those patients with tumors < or = 1 cm compared with patients with tumors > or = 1.1 cm, regardless of whether tumor size was measured by macroscopic or microscopic examination. The 10-year actuarial rate of freedom from distant recurrence (FFDR) was 91% for lymph node negative patients with macroscopic tumors measuring < or = 1.0 cm compared with 77% for patients with macroscopic tumors measuring > or = 1.1 cm (P = 0.07). When measured microscopically, the rates were 96% and 72%, respectively (P = 0.001). There often is a discrepancy between microscopic tumor size and macroscopic tumor size. T1 tumors have a substantial risk of axillary lymph node metastasis whether measured macroscopically or microscopically. Among those patients with pathologic lymph node negative tumors who are not treated with systemic adjuvant therapy, microscopic invasive tumor size is a better predictor of 10-year FFDR than macroscopic tumor size. There is a substantial risk of distant failure for patients with tumors whose invasive component microscopically measure > or = 1.1 cm, whereas the prognosis for patients with tumors that microscopically measured < or = 1 cm is excellent. These results suggest that the microscopic size of the invasive component of breast carcinomas < or = 2.0 cm routinely should be reported.

Correlation of tumor size and axillary lymph node involvement with prognosis in patients with T1 breast carcinoma

BACKGROUND The prognosis of patients with T1 breast carcinoma remains controversial. Some studies have shown a low risk of lymph node metastasis and distant failure whereas others have not, possibly due to differences in the definition of tumor size. In this study, the authors assessed the relation between macroscopic tumor size, microscopic invasive tumor size, axillary lymph node involvement, and prognosis in a group of patients with clinically lymph node negative disease. METHODS Between 1968 and 1986, 1865 women with American Joint Committee on Cancer clinical Stage I or II infiltrating carcinoma of the breast were treated at the Joint Center for Radiation Therapy with conservative surgery and radiation therapy. The study population was limited to 118 patients with clinically negative axillary lymph nodes for whom the macroscopic pathologic tumor size was identified unambiguously as being ≤ 2.0 cm, who underwent an axillary lymph node dissection with at least 6 lymph nodes sampled, and for whom the microscopic size of the invasive component could be determined. The median follow-up time for surviving patients was 134 months (range, 90-208 months). No patients with pathologically negative axillary lymph nodes received systemic therapy. RESULTS Macroscopic and microscopic tumor sizes differed by > 5 mm in 17 patients (14%), by 3-5 mm in 24 patients (20%), and by ≤ 2 mm in 77 patients (65%). The macroscopic tumor size was smaller than the microscopic size in 37 patients (31%), larger in 55 patients (47%), and equal in 26 patients (22%). Pathologic axillary lymph node involvement was present in 21% of all patients. The risk of lymph node involvement was not significantly different for those patients with tumors ≤ 1 cm compared with patients with tumors ≥ 1.1 cm, regardless of whether tumor size was measured by macroscopic or microscopic examination. The 10-year actuarial rate of freedom from distant recurrence (FFDR) was 91% for lymph node negative patients with macroscopic tumors measuring ≤ 1.0 cm compared with 77% for patients with macroscopic tumors measuring ≥ 1.1 cm (P = 0.07). When measured microscopically, the rates were 96% and 72%, respectively (P = 0.001). CONCLUSIONS There often is a discrepancy between microscopic tumor size and macroscopic tumor size. T1 tumors have a substantial risk of axillary lymph node metastasis whether measured macroscopically or microscopically. Among those patients with pathologic lymph node negative tumors who are not treated with systemic adjuvant therapy, microscopic invasive tumor size is a better predictor of 10-year FFDR than macroscopic tumor size. There is a substantial risk of distant failure for patients with tumors whose invasive component microscopically measure ≥ 1.1 cm, whereas the prognosis for patients with tumors that microscopically measured ≤ 1 cm is excellent. These results suggest that the microscopic size of the invasive component of breast carcinomas ≤2.0 cm routinely should be reported. Cancer 1998;83:2502-2508. © 1998 American Cancer Society.

Linac radiosurgery at the joint center for radiation therapy

The Joint Center for Radiation Therapy (JCRT) has treated intra-cranial lesions with high-dose single fraction stereotactic radiosurgery (SRS) since 1986 and with multi-fraction stereotactic radiotherapy (SRT) since 1992. This paper describes the JCRT techniques for treatment planning and delivery for SRS, and to a limited extent for SRT. LINAC quality assurance, treatment delivery, and patient management for stereotactic radiosurgery and stereotactic radiotherapy technique are closely related at the JCRT, although differences exist. An historical retrospective of our experience with stereotactic techniques including imaging modalities, treatment planning techniques, optimization methods, and treatment delivery is presented. Three treatment planning approaches, single isocenter, multiple isocenter, and micro-jaw field shaping are used to demonstrate the capabilities and technical dosimetric features of each approach. The major planning differences and clinical of each technique are described. From our experience, lesions less than 3.0 cm in maximum extent are well treated with circular fields using either a single or multiple isocenter configuration. Lesions greater than 3.0 cm in maximum extent usually benefit from field shaping using the micro-jaws. For these large lesions, the shaped field approach typically improves the dose homogeneity as well as reduces the amount of healthy brain irradiated. Our physicians choose between the three techniques to meet the desired clinical outcome the patient’s situation requires.

Assessment of outcome prediction models for patients with localized prostate carcinoma managed with radical prostatectomy or external beam radiation therapy

A clinical staging system for localized prostate carcinoma that provides reliable information on which management decisions regarding an individual patient can be based is lacking. This study compared the abilities of all published proposed clinical staging systems to predict time to prostate specific antigen (PSA) failure after radical prostatectomy or external beam radiation therapy for clinically localized prostate carcinoma. A total of 1441 clinically localized prostate carcinoma patients who were managed with radical prostatectomy at the University of Pennsylvania in Philadelphia (n = 688) or the Brigham and Women's Hospital in Boston (n = 288) or with external beam radiation therapy at the Joint Center for Radiation Therapy in Boston (n = 465) were entered into this study. Patients who received adjuvant or neoadjuvant hormonal or radiation therapy were excluded. Akaike's Information Criterion (AIC) and Schwartz Bayesian Criterion (SBC) estimates, which are comparative measures, were calculated for each clinical staging system. Pairwise comparisons of the AIC and SBC estimates for the most predictive clinical staging systems were performed using a formal bootstrap technique with 2000 replications. Both the staging system based on the risk score and the staging system based on the calculated volume of prostate carcinoma and PSA (cVCa-PSA) optimized the prediction of time to posttreatment PSA failure. The cVCa-PSA system, however, provided a more clinically useful stratification of outcome. Improved clinical staging for patients with localized prostate carcinoma may be possible with parameters obtained during routine evaluation. Validation by other investigators is underway.

Radiation-Associated Morbidity in Patients Undergoing Small-Field External Beam Irradiation for Prostate Cancer

Purpose: To quantify complication rates after small-field external beam irradiation for adenocarcinoma of the prostate in a uniformly treated patient population with long follow-up using a simple tool designed to identify subtle treatment-related side effects; and to identify clinical and technical variables associated with increased morbidity after irradiation. Methods and Materials: A total of 441 patients with nonmetastatic adenocarcinoma of the prostate treated at the Joint Center for Radiation Therapy between 1985 and 1989 were eligible for analysis. Gastrointestinal, genitourinary, and sexual function were assessed retrospectively using a patient self-scoring, five-grade toxicity scale. Seven clinical and 15 technical variables were recorded for each patient. The association between the clinical and technical variables and rectal, bladder, and sexual side effects was examined. The 375 patients who received small-field (<12.5 × 12.5-cm) external beam irradiation via a four-field box on a 6-MV ( n = 74, or 20% of patients), 8-MV ( n = 140, or 37%), or 15-MV ( n = 161, or 43%) linear accelerator form the basis for the study. Ninety-one percent of patients received treatment with 1.8–2.0 Gy fractions to a delivered dose of at least 66 Gy. Follow-up was complete through 62 months in living patients, with five (1%) of the entire group lost to follow-up. Results: A total of 137 of 354 evaluable patients (39%) reported rectal complications after treatment; however, 20 patients(6%) had heme-positive stools as their only symptom and 66 (19%) had mild symptoms not requiring treatment. Only 14% of the entire group required intervention. Of 356 patients, 117 (33%) evaluable for bladder complications developed genitourinary changes: In 14 patients (4%) asymptomatic hematuria occurred, 71 (20%) had mild symptoms not requiring treatment, and 32 (9%) required treatment. Of the 171 patients who were potent prior to radiation, 106 (62%) reported impotence after treatment. No statistically significant association was identified between any clinical or technical variables (including machine energy) assessed and complications. Conclusions: In this retrospective review, treatment-related bowel and bladder side effects were not identified in the majority of patients despite the use of a grading system designed to identify subtle changes. Impotence, however, was common. Although pretreatment clinical characteristics varied among patients, they could not be used to predict the subsequent development of complications. The only treatment-related characteristic that varied in this study was machine energy, which did not correlate with complications.

No long-term increase in cardiac-related mortality after breast-conserving surgery and radiation therapy using modern techniques.

To determine whether left-breast irradiation using modern techniques after breast-conserving surgery leads to an increased risk of cardiac-related mortality. Between 1968 and 1986, 1,624 patients were treated for unilateral stage I or II breast cancer at the Joint Center for Radiation Therapy, Harvard Medical School, Boston, MA, with conservative surgery and breast irradiation. Seven hundred forty-five patients with a potential follow-up of at least 12 years were analyzed. Clinical, pathologic, and treatment characteristics were compared between the 365 patients (49%) who received left-sided irradiation and the 380 patients (51%) who received right-sided irradiation. The relationship between left-sided breast irradiation and the risk of nonbreast cancer- and cardiac-related mortality was examined. There was no significant difference in the distribution of clinical, pathologic, or treatment characteristics between the two groups, with the exception of a small difference in pathologic tumor size (medians, left, 2.0 cm, right, 1.5 cm; P = .007). At 12 years, a majority of patients still were alive. Slightly more patients with left-sided tumors had died of breast cancer (31% v 27%; P = NS). Equivalent proportions from each group died of nonbreast cancer causes (11%), including nine patients (2%) from each group who died from cardiac causes. The risk of cardiac mortality did not increase as time after treatment increased for patients who received left-sided irradiation compared with right-sided irradiation. A model that controlled for clinical, pathologic, and treatment differences showed no significant increase in any category of cause of death (breast, cardiac, or other) for patients who received left-sided irradiation. These results suggest that modern breast radiotherapy is not associated with an increased risk of cardiac-related mortality within at least the first 12 years after treatment.

Skin recurrences after breast-conserving therapy for early-stage breast cancer.

To assess the frequency and prognosis of skin recurrences after breast-conserving therapy (BCT) compared with other breast recurrences. From 1968 to 1986, 1,624 patients with unilateral stage I or II breast cancer treated with BCT at the Joint Center for Radiation Therapy (Boston, MA) underwent gross tumor excision and received a dose of > or = 60 Gy to the tumor bed. Skin recurrences (SR) were defined as breast recurrences without associated parenchymal disease. An invasive breast recurrence with any parenchymal disease noted clinically or radiographically was scored as an other breast recurrence (OBR). Median follow-up for survivors was 137 months. SR represented 8% (18 of 229) of all breast recurrences and occurred in 1.1% of all patients. The outcome after local recurrence was different for patients with SR and invasive OBR. Patients with SR more frequently had uncontrolled local failure (50%; 9 of 18) than did patients with OBR (14%; 26 of 188) (P = .0007). Forty-four percent (8 of 18) of patients with SR had distant metastasis simultaneously or within 2 months of the recurrence compared with 5% (9 of 188) of invasive OBR patients (P < .0001). For patients without distant metastasis at the time of recurrence, the 5-year actuarial rate of development of distant metastasis was 60% for SR patients compared with 39% for invasive OBR patients (P = .07), and the corresponding 5-year actuarial survival rates beyond the time of local failure were 51% and 79%, respectively (P = .06). In contrast to other types of invasive breast recurrence after breast-conserving therapy, skin recurrences are rare and are associated with a significantly higher rate of distant metastasis and uncontrolled local disease as well as a lower rate of survival.

A blueprint for linking academic oncology and the community.

The processes by which academic medicine will train the next generation of physicians and develop new knowledge have brought to the forefront the relationship between academic medical centers and community hospitals and practitioners. Over the past thirteen years, the Harvard Medical School Joint Center for Radiation Therapy (JCRT) has developed an integrated radiation oncology program designed to serve simultaneously the needs of the community, teaching hospitals, medical schools, and faculty. The structure and function of this program are described here, as are the challenges posed by the highly competitive health care marketplace. We believe that long-term vision should guide short-term goals. The success of academic-community collaborative programs depends not only on the good will and vision of the participants but also on the medical administration, academic leadership, policy makers, and politicians who define the principles and rules by which cooperation within the health care industry occurs.

OUTCOME BASED STAGING FOR CLINICALLY LOCALIZED ADENOCARCINOMA OF THE PROSTATE

Some patients with clinically localized prostate cancer are not cured after radical prostatectomy because of the presence of occult systemic disease. The American Joint Commission on Cancer staging classification for prostate cancer does not reliably distinguish between clinically localized patients who are likely or unlikely to be cured after local therapy. This project was undertaken to develop a staging system capable of predicting long-term outcome after radical prostatectomy on the basis of the clinical parameters obtained routinely during the standard workup for patients with adenocarcinoma of the prostate. A total of 688 clinically localized prostate cancer patients managed with a radical retropubic prostatectomy for adenocarcinoma of the prostate between 1989 and 1996 was evaluated for clinical features predictive of time to prostate specific antigen (PSA) failure using a Cox regression multivariate analysis. A recently defined clinical factor called the calculated prostate cancer volume and its ability to predict time to PSA failure in conjunction with PSA, biopsy Gleason score and clinical stage were evaluated. The calculated prostate cancer volume (p <0.0001) and the pretreatment PSA (p <0.001) provided the optimal staging system for predicting freedom from PSA failure after radical prostatectomy. The calculated prostate cancer volume and PSA may provide clinically useful information regarding outcome after radical prostatectomy, enabling the selection of a therapeutic approach for an individual patient with clinically localized disease. Validation of this staging system is needed.