Sidney H. Sobel

Definitive treatment of anal-canal carcinoma by means of radiation therapy and chemotherapy

In the light of the relatively poor response of squamous-cell carcinoma of the anus to surgery, an alternative method of treatment has been sought. During the past five years, in a series of 19 patients, the first four were treated by a combination of preoperative irradiation, 5-fluorouracil (5-FU) and mitomycin C as radiosensitizers plus surgery. As a result of complete responses at the time of surgery of all these patients, 15 additional patients have been treated by definitive radiotherapy combined with 5-FU and mitomycin C, thereby avoiding abdominoperineal resection. Eighteen patients had local control, and the one treatment failure is discussed. The method of treatment is described, and recommendations are made concerning techniques to be used or to be avoided.

Tumor persistence as a predictor of outcome after radiation therapy of head and neck cancers

Abstract Tumor clearance or persistence was assessed at different time intervals during, at the completion of, and after radiation therapy in order to predict local control of failure in 144 cases of head and neck cancer. The rate of tumor clearance (TC) during treatment is less important than is complete tumor clearance in predicting for local control (LC). If tumor clearance occurred within one to three months following completion of treatment, local control could be predicted in cancers of the oral cavity, oropharynx and hypopharynx with approximately 80, 70 and 50% reliability, respectively. However, tumor persistence (TP) (evidenced by induration and surface irregularity) was a highly accurate predictor of failure (90–100%) at this assessment interval. Persistence of induration at the completion of treatment is inaccurate in the assessment of eventual local failure (LF), since local control eventually is achieved in 25–35% of the cases.

Treatment of rectal carcinomas by means of endocavitary irradiation: a progress report

Treatment of rectal carcinomas with endocavitary irradiation is now an established method in the United States and is an important advance in the curative management of patients with selected cancers of the rectum that should be available to all such patients. Excellent palliation can also be achieved in many cases with advanced local disease. The total experience at Highland Hospital, Rochester, New York, is over 70 cases. Now that there are more centers using this method of treatment, an awareness of some of the problems and pitfalls encountered at Highland Hospital becomes relevant.

Combined betaseron R (recombinant human interferon beta) and radiation for inoperable non-small cell lung cancer

PURPOSE Based on in vitro evidence of radiosensitization by Betaseron (beta-IFN), a Phase I/II study was undertaken to determine toxicity and response using combined radiation (RT) and B-IFN in patients with unresectable Stage III and nonsmall cell lung cancer. METHODS AND MATERIALS Varying doses of beta-IFN(10 to 90 x 10(6) IU) were administered IV immediately preceding RT on the first three days of weeks 1, 3, and 5. The RT dose was 1.8 Gy/day, 5 days/week for a total of 54 or 59.4 Gy. RESULTS Thirty-nine patients were entered, 32 of whom were evaluable. The median follow-up time at time of analysis was 60 months. Responses were based on CT scan. The response rate for the total group was 81% with 44% achieving complete response. Seventy-eight percent of patients with complete response survived a minimum of 21 months. Twenty-six patients had Stage III A/B disease with a median tumor size of 6.5 cm. and median survival was 19.7 months. The 5-year actuarial survival for this group was 31%, with a plateau persisting after 3 years. There were no treatment related deaths nor any event of life threatening toxicity. Of eight patients surviving 3-5 years, no long-term toxicity has been observed. Karnofsky indices were 90-100 and respiratory symptoms were minimal. CONCLUSION beta-IFN is well-tolerated. Response and survival rates are sufficiently encouraging to warrant further investigation in a randomized trial which has been accepted as an RTOG study awaiting drug availability.

Treatment of breast cancer with segmental mastectomy alone or segmental mastectomy plus radiation

A retrospective review of the outcome of treatment for primary, Stage I and II breast cancer with segmental mastectomy (SGM) alone or segmental mastectomy plus postoperative irradiation (SGM + RT) at four Rochester, New York, city hospitals is reported. Between January 1971 and March 1984, 99 women were treated with SGM and 146 with SGM + RT. Groups were similar regarding significant clinical and histologic prognostic factors; they differed, however, in that the SGM group was considerably older (means = 72) than the SGM + RT group (means = 56). Among SGM patients, local and total locoregional failure was 26.44 and 35.2%, respectively. Local and total locoregional failure (7.6 and 12.4%, respectively) was significantly reduced among patients treated with SGM + RT (p less than 0.0001). Among SGM patients, there was scant advantage in enlarging the extent of resection from local excision (29.5% local failure) to wide local excision (27.3%) to quadrantectomy (22.2%). Among women receiving SGM + RT, similar rates of local failure occurred among patients receiving local excision (15.5%) and wide local excision (12.5%). By contrast, only 2.8% of those receiving quadrantectomy failed. Results are viewed as supportive of findings of NSABP-B06. Findings suggest that SGM constitutes inadequate treatment of Stage I and II breast cancer. Locoregional failure rates of 30-40% may be reduced to around 10% with postoperative irradiation.

Eastern Cooperative Oncology Group: A Comparison of Adjuvant Doxorubicin and Observation for Patients With Localized Soft Tissue Sarcoma

Forty-seven patients with stage I, II, or III soft tissue sarcoma were entered into a prospective randomized Eastern Cooperative Oncology Group (ECOG) adjuvant protocol. Eligibility included conservative or radical primary treatment for local cure. Patients were then randomized to control or Adriamycin (Adria Laboratories, Columbus, OH). Adriamycin was administered at 70 mg/m2 (slow push, every 3 weeks for seven courses for a maximum of 550 mg/m2). To date, 32 patients, 17 males and 15 females, with an age range of 17 to 75 years (median, 44 years) have been followed sufficiently long to be included in this analysis. Nine patients have died. The median follow-up of the remaining 23 patients is 30 months (range, 2 to 50 months). Survival was not significantly different between Adriamycin or control. However, the disease-free interval was slightly different in favor of observation. This preliminary report does not support the hypothesis that Adriamycin is an effective adjuvant therapy for soft tissue sarcoma. Due to the small numbers, these results must be interpreted in relation to our ability to detect a difference, if in fact one existed. These preliminary data suggest that adjuvant Adriamycin not be used outside the confines of a clinical trial such as the current intergroup adjuvant sarcoma study.

Treatment of rectal carcinomas by means of endocavity irradiation.

Direct contact irradiation may be used in the curative treatment of patients with carefully selected early rectal lesions. With earlier diagnosis, a large number of patients may present with suitable lesions. The treatments last three minutes and are administered every two weeks to a total dose of 9,000 rad to 12,500 rad. The patients require no general anesthesia or hospitalization and may continue working during this treatment. There appears to be no risk of morbidity or mortality. The rectum is preserved. Most beneficial of all to the patient, a colostomy is avoided, although later surgery is not precluded for local failures. It has been found that recurrence, should it occur, appears within the 18 months immediately following treatment. Good palliation can be achieved in some cases for patients with metastatic disease, for their local symptoms. We believe that the endocavity method of irradiation contributes an important advance in the management of patients with cancer of the rectum and feel it should be available universally.

Treatment of rectal carcinomas by means of endocavitary irradiation

Treatment of rectal carcinomas with endocavitary irradiation is now an established method in the United States and is an important advance in the curative management of patients with selected cancers of the rectum that should be available to all such patients. Excellent palliation can also be achieved in many cases with advanced local disease. The total experience at Highland Hospital, Rochester, New York, is over 70 cases. Now that there are more centers using this method of treatment, an awareness of some of the problems and pitfalls encountered at Highland Hospital becomes relevant.

John Call Dalton, Jr., MD America’s first neurophysiologist

Article abstract Before the discoveries of John Call Dalton, Jr., MD (1824–1889), innervation of laryngeal muscles, long-term effects of cerebellar lesions, and consequences of raised intracranial pressure were poorly understood. Dalton discovered that the posterior cricoarytenoid muscles adducted the vocal cords during inspiration. He confirmed Flourens’ observations that acute ablation of the cerebellum of pigeons caused loss of coordination. Dalton observed that properly cared for pigeons gradually recovered “coordinating power.” Dalton observed that prolonged raised intracranial pressure caused tachycardia and then fatal bradycardia in dogs. Before Dalton published his photographic atlas of the human brain, neuroanatomy atlases were sketched by Europeans and imported into the United States. Dalton’s atlas of the human brain contained precise photographs of vertical and horizontal sections that equal modern works. Before Dalton introduced live demonstrations of animals, physiology was taught by recitation of texts only. Dalton was the first American-born professor to teach physiology employing demonstrations of live animals operated on under ether anesthesia. He wrote an essay advocating experimentation on animals as the proper method of acquiring knowledge of function and that humane animal experimentation would ultimately improve the health of man and animals. His eloquent advocacy for humane experimental physiology quelled attacks by contemporaneous antivivisectionists. Dalton was America’s first experimental neurophysiologist.