Gene Kopelson

Medulloblastoma: The identification of prognostic subgroups and implications for multimodality management

For 43 medulloblastoma patients who had five‐and ten‐year actuarial survival rates of 56%, prognostic factors of statistical significance included: T‐stage (82% T1,2; versus 46% T3,4; P < 0.02), M‐stage (63% M0,1 versus 0% M2,3; P < 0.03), and histopathologic tumor score (TS, based upon necrosis, desmoplasia, cytoplasmic processes, and mitoses) (81% TS ⩽ 5 versus 41% TS ⩾ 6; P < 0.05). Posterior fossa local control rates were also function of T‐stage (90% T1,2 versus 38% T3,4) and TS (83% TS ⩾ 5 versus 38% TS ⩾ 6). Combining TS with T‐stage, patients fell into three prognostic and local control groups, which may have different future management implications: Small (T1,2) tumors of favorable (TS ⩽ 5) histology had a 92% ten‐year actuarial survival rate with 100% (8/8) local control; no change from current management is suggested. For the intermediate prognosis group (T1,2‐TS ⩽ 6 or T3,4‐TS ⩾ 5 with 67% and 70% survival, respectively), increasing the irradiation dose alone may improve survival because these tumors exhibited an irradiation dose‐response relationship. However, it is the poor prognosis group (T3,4‐TS ⩾ 6 with 42% survival) which might be suitable for future adjuvant chemotherapy or radiosensitizer trials since there is no evidence that higher irradiation doses improve local control. This article identifies prognostic subgroups based on histologic type and TM staging in medulloblastoma patients which potentially may be utilized to improve therapeutic results, and confirms the value of staging patients with central nervous system malignancies.

Intramedullary spinal cord astrocytoma versus glioblastoma: the prognostic importance of histologic grade.

Fourteen patients with intramedullary spinal cord astrocytoma (Grades I, II) or glioblastoma (Grades III, IV) were seen at a major referral center over a 19‐year period. Although similar surgical and radiotherapeutic techniques were used for each group, the nine patients with astrocytoma had a five‐year actuarial survival rate of 89% with five patients alive and well at least five years after treatment; none of the five patients with glioblastoma survived past three years. Histologic grade is the most important factor affecting prognosis for patients with intramedullary spinal cord astrocytomas or glioblastomas, and long‐term survival can be achieved postirradiation for many patients with astrocytomas with improved neurologic functioning in most.

Medulloblastoma in adults. Improved survival with supervoltage radiation therapy

During the period from January 1962‐June 1979, 17 adults (⩾16 years of age) received postoperative supervoltage neuraxis radiation therapy for medulloblastoma. An actuarial five‐ and ten‐year survival rate of 46% was achieved, and the major site of recurrence postirradiation was in the posterior fossa. Compared to previous pediatric series, adults may demonstrate more visceral metastases and fare less well after tumor recurrence. Compared to prior series of adult patients, the demonstrated improved survival is attributed to increased doses delivered to the posterior fossa.

Infratentorial glioblastoma: the role of neuraxis irradiation

The patterns of clinical-and autopsy-documented tumor spread were evaluated for 15 patients with biopsy-proven infratentorial (8 cerebellar, 2 brainstem, 5 intramedullary spinal cord) glioblastoma. No patient developed clinical nor autopsy evidence of subarachnoid dissemination, even though no patient had received craniospinal axis irradiation. Fully 14 of the 21 previously reported patients with subarachnoid dissemination from infratentorial glioblastoma had this diagnosis made only at autopsy. The overall poor prognosis at present (8% 3-year survival from the present series and recent literature) along with the demonstrated pattern of local-regional aggressiveness as the major form of initial spread and post-irradiation recurrence, suggests that routine craniospinal axis irradiation may not be indicated for most patients with infratentorial glioblastoma.

Extra-hepatic biliary tract metastases from breast cancer

Abstract A retrospective review was conducted of 49 breast cancer patients who were seen at the Massachusetts General Hospital from 1962 to 1978 and who developed biliary tract metastases. Although these findings were incidental at autopsy in 21 patients, clinical evidence of extra-hepatic biliary involvement developed in 28. This was documented radiographically, surgically, and/or confirmed at autopsy. Although most patients had previous or concurrent nonbiliary tract metastases, in 6 patients the initial site of failure was in the extra-hepatic biliary system. Analysis of the 28 patients in the clinical group revealed that initial management with radiation therapy alone produced a response in 3 of 6 patients. However, when radiation was coupled with bypass surgery and/or adjuvant chemotherapy, a response occurred in 3 of 3; the total radiation therapy response rate was 6/9. Chemotherapy given either alone or in combination with surgery produced a response in only one of 7 patients. All 4 irradiated patients who were treated with a time-dose-fractionation (TDF) > 40 had a complete response compared to a complete response in only 2 of 8 with a TDF ≤ 40. The median survival of the irradiated group was 6 months compared to 3.3 months in the treated-unirradiated patients and 0.7 months in the untreated patients. The onset of jaundice in a breast cancer patient does not necessarily indicate progressive hepatic involvement. Patients with extrahepatic metastatic obstruction are being recognized increasingly and should be treated vigorously, especially since such patients with no liver parenchymal involvement have a greater survival (median 6 months) than those with liver involvement (median 1.8 months).

Primary and adjuvant radiation therapy in gallbladder and extrahepatic biliary tract carcinoma

The natural history and pathways by which carcinomas of the gallbladder and extrahepatic bile ducts spread after attempted curative surgery offer a rationale for postoperative radiation therapy. We review: 1) the increasing use of primary-curative radiation therapy for these cancers, along with 2) the early results of innovative intraoperative irradiation and the transluminal insertion of radioactive sources into transhepatic catheters, 3) the efficacy of irradiation for metastases to the portahepatis, and 4) the overall effects of irradiation on the gallbladder and extrahepatic biliary system.

Radiation therapy for postoperative local-regionally recurrent lung cancer

Abstract Twenty-four patients with post-resection local-regionally recurrent non-small-cell-undifferentiated lung carcinoma received external beam radiation therapy over an 18-year period at the Department of Radiation Medicine, Massachusetts General Hospital. No patient had demonstrable distant metastases; the median time interval from initial surgery to recurrence was 15 months. Fully 1724 patients (71 %) had histopathologic/cytologic proof of recurrence, and none had either prior, concurrent, nor adjuvant chemotherapy. The 5-year actuarial survival rate for the 24 patients was 10%; our 2 long term survivors each had early-stage initial lesions: (one T 2 N 0 patient with later hilar/supraclavicular recurrence who received a dose Time-Dose-Fractionation (TDF) 67 and lived 7.3 years with normal chest x-ray (CXR) at death; the other patient, T 1 N 0 with first stump/hilar recurrence removed surgically but had later stump re-recurrence, received a dose TDF 67 and lived 9.5 years with normal CXR at death). In 11 patients local tumor control was achieved, documented by autopsy and/or CXR at death or last follow-up. complete and permanent disapperance was achieved post-irradiation for 15/31 thoracic symptoms (48%). Of 8 patients with isolated bronchial stump ± adjacent hilum recurrence, local control was achieved in 5.

Preoperative Irradiation, Lymphadenectomy and 125Iodine Implant for Patients with Localized Prostatic Carcinoma: a Correlation of Implant Dosimetry with Clinical Results

The 30 patients with clinically and surgically localized prostatic carcinoma who were selected for treatment by a short course of preoperative irradiation (1,050 rad), pelvic lymphadenectomy and 125iodine implant have been followed for 1 to 4 years. Perioperative morbidity (10 per cent), postimplant impotence (11 per cent), lymphedema (17 per cent), tumor recurrence (4 per cent) and distant metastasis (4 per cent) have been minimal to date. However, urinary irritative symptoms, which usually subsided in 6 to 9 months, occurred in half of the patients and correlated with implant volume. Total dose and total dose per unit of implanted activity were calculated. Of the various implant parameters evaluated implant dose homogeneity has corrrelated with the rate of tumor regression.

Radiation tolerance of the spinal cord previously-damaged by tumor and operation: Long term neurological improvement and time-dose-volume relationships after irradiation of intraspinal gliomas

Of 26 patients with intramedullary spinal cord gliomas (9 astrocytomas, 5 glioblastomas, 12 ependymomas) seen at the Massachusetts General Hospital from 1962--1980, 24 were irradiated (21 initially and 3 after post-surgical recurrence). Those 19 patients who survived at least 1 year after completion of irradiation were evaluated for post-irradiation neurological changes. No patient developed radiation myelopathy. Return to a permanently and completely normal neurological status occurred for 33/51 (65%) of pre-irradiation neurological deficits. The major cause of post-irradiation neurological deterioration was tumor recurrence. Although 18/19 patients had their thoracic or lumbar spinal cords irradiated, each with field sizes greater than 10 cm, spinal cord doses approaching, equalling, or occasionally exceeding various definitions of spinal cord tolerance were tolerated well without evidence of radiation myelopathy. Spinal cords of patients with intramedullary gliomas, often with major neurological deficits prior to irradiation, may be treated safely to doses approaching or equalling spinal cord tolerance levels. These doses are expected to locally control most ependymomas and astrocytomas without an increased risk of radiation myelopathy. Caution should be observed if doses higher than this are contemplated in an attempt to cure a glioblastoma, because the 5% tolerance level of the damaged spinal cord remains to be defined.

Bilateral breast cancer: radiation therapy results and technical considerations

Abstract A retrospective review was done of 34 women with bilateral breast carcinoma (11 synchronous, 23 metachronous) who received bilateral breast irradiation (breast, chest wall, and/or internal mammary chain (IMC) nodes) from 1964–1979. For the 31 curative patients, the 10-year actuarial survival rate after completion of irradiationh to the second primary was 6796 (8096 in the group having bilateral radical comprehensive irradiation ). Based upon the development of bilateral medial subcutaneous fibrosis/necrosis in 315 long-term (≥ 5 year) survivors, various technical problems unique to bilateral breast irradiation were examined: In metacbronous presentations, the dose to the contralateral subcutaneous medial tissue was determined as a function of the distance across the midline that the ipsilateral medial tangential border and the ipsilateral medial direct IMC border is placed and the total dose that this point should receive if future contralateral IMC irradiation is required also. In synchronous presentations the doses to the spinal cord and anterior pericardium were determined for bilateral IMC irradiation as a function of modality, field width and energy. Suggestions for solving these technical problems are made, and the importance of permanent skin markings documenting portal placement to aid in possible future contralateral breast irradiation is stressed.