Arthur H. Knowlton

Therapy of locally unresectable pancreatic carcinoma: a randomized comparison of high dose (6000 rads) radiation alone, moderate dose radiation (4000 rads + 5-fluorouracil), and high dose radiation + 5-fluorouracil: The Gastrointestinal Tumor Study Group.

One‐hundred‐ninety‐four eligible and evaluable patients with histologically confirmed locally unresectable adenocarcinoma of the pancreas were randomly assigned to therapy with high‐dose (6000 rads) radiation therapy alone, to moderate‐dose (4000 rads) radiation + 5‐fluorouracil (5‐FU), and to high‐dose radiation plus 5‐FU. Median survival with radiation alone was only 51/2 months from date of diagnosis. Both 5‐FU‐containing treatment regimens produced a highly significant survival improvement when compared with radiation alone. Forty percent of patients treated with the combined regimens were still living at one year compared with 10% of patients treated with radiation only. Survival differences between 4000 rads plus 5‐FU and 6000 rads plus 5‐FU were not significant with an overall median survival of ten months. Significant prognostic variables, in addition to treatment, were pretreatment performance status and pretreatment CEA level.

Randomized phase II clinical trial of adriamycin, methotrexate, and actinomycin-d in advanced measurable pancreatic carcinoma. A gastrointestinal tumor study group report

Sixty‐six patients with advanced pancreatic carcinoma were randomized to receive single agent chemotherapy with either adriamycin, methotrexate, or actinomycin‐D using conventional dose, route and schedule of administration. All patients had measurable lesions which were used for objective assessment of response. For adriamycin, 2 of 25 patients (8%) evidenced a partial response (2 of 15 (13%) previously untreated patients). One of 25 patients treated with methotrexate and one of 28 who received actinomycin‐D responded. The duration of responses ranged from 43–64 days for those patients with no chemotherapy prior to study entry. The median survival of patients who received adriamycin as initial treatment was 12 weeks compared to 8 weeks for methotrexate and 6 weeks for actinomycin‐D therapy.

Supradiaphragmatic Hodgkin's disease: significance of large mediastinal masses.

Abstract In order to assess the significance of large mediastinal masses in patients with Hodgkins disease, we analyzed all patients with pathological stage (PS) IA or IIA disease evaluated and treated at Yale between 1969 and 1978. There were 131 such patients treated initially with radical radiotherapy only, combination chemotherapy being reserved for those who failed radiation. Actuarial 5 and 10 year survivals were 95%. The presence of a mediastinal mass reglardless of size did not affect survival. Relapse-free survival was 77% at 5 years, 74% at 10 years in the entire group. Patients with any mediastinal involvement had a 65% relapse-free survival, 72% if the mass was 33%. These differences are suggestive of a greater tendency of such patients to fail radiotherapy but the differences were not statistically significant. Patients who did fail radiotherapy were for the most part successfully retreated with combined modality therapy (chemotherapy and radiation), accounting for the overall survival of 95%. Only 6 patients died of causes related to Hodgins disease and 2 of these deaths were related to combined modality therapy complications. Because of the serious potential long term consequences of combined modality treatment, it should be used with great caution and on an individual basis only in PSIA and IIA patients.

Toxicity associated with adjuvant postoperative therapy for adenocarcinoma of the rectum

The Gastrointestinal Tumor Study Groups (GITSG) adjuvant rectal carcinoma study compared four postoperative treatment regimens: (1) control (no adjuvant therapy); (2) chemotherapy alone consisting of pulses of 5‐fluorouracil and methyl CCNU for 18 months; (3) pelvic and perineal radiotherapy using parallel opposed fields with 4000 rad in 4.5 to 5 weeks or 4800 rad in 5 to 5.5 weeks; and (4) a combination of both modalities. The results of this study are published elsewhere and show a significantly reduced recurrence rate and prolonged disease‐free survival time for the combined modality arm compared with the no therapy arm. Severe toxicity in the combined therapy arm was significantly worse (P < 0.001) than in either single modality arm. Most of the differences in toxicity experienced between the three regimens involved diarrhea, thrombocytopenia, and leukopenia. Analysis of all parameters of radiotherapy quality assurance data was not significantly associated with toxicity. Radiation enteritis was noted in 5 patients of 96 (5.2%) in the two arms containing irradiation. All five required laparotomy. The two enteritis fatalities occurred late at 605 and 1000 days after start of combined modality treatment, respectively. One other patient on the chemotherapy arm died of acute nonlymphocytic leukemia. The authors conclude that combined radiotherapy and chemotherapy, although significantly more effective in reducing recurrence than no therapy, is significantly more toxic than single‐modality therapy in many parameters, although most of the toxicity is transient and therefore not limiting. Late complications, which are less reversible and therefore much more important than early reactions, and radiation enteritis in this study were relatively uncommon. This schedule of combined modality therapy is not only effective but appears to have tolerable toxicity, because of the relative lack of late effects.

Endodermal sinus tumor of the infant vagina

A case of endodermal sinus tumor of the infant vagina is reported with long-term survival after successful therapy by surgery, chemotherapy, and radiation. The previous 26 reported cases are reviewed and the problems of therapy and long-term management are discussed. Therapy of these tumors should be monitored by alpha-fetoprotein radioimmunoassay.

Perineal effects of postoperative treatment for adenocarcinoma of the rectum

Nine (4%) first recurrences that involved the perineum were identified in a randomized study of 202 patients treated by no further therapy, chemotherapy only, radiotherapy only, combined radiotherapy and chemotherapy, following complete surgical excision of adenocarcinoma of the rectum. Six of these were in unirradiated patients and in two of the three irradiated patients the perineum was included in the treatment volume. Eight of the nine patients were male and all nine had received abdominoperineal resection (APR). Our quality assurance procedures identified 22 of 96 irradiated patients in whom the perineum was grossly outside the fields. Sixteen of these had undergone APR. As only one of these 16 relapsed in the perineum no definite effect of the surgical procedure on the likelihood of perineal recurrence could be demonstrated. Examination of the pathology reports revealed that 28 patients undergoing APR had tumors within 2 cm of the anorectal junction (pectinate line). Five (17.8%) developed perineal recurrence compared with 4 (3.6%) of 110 patients whose tumors were more than 2 cm from the anus (p less than 0.02-Fisher exact test). No survival differences could be demonstrated between those receiving perineal irradiation and those not but perineal irradiation was associated with toxicity with at least nine (12.2%) out of 74 developing severe complications directly related to the perineum. The routine inclusion of the perineum in postoperative pelvic irradiation fields for all cases of adenocarcinoma of the rectum is questioned. Our current policy following APR includes optional coverage of the perineum for those tumors more than 5 cm from the anorectal junction.

Effect of radiation on cell-mediated cytotoxicity and lymphocyte subpopulations in patients with ovarian carcinoma.

Lymphocyte subpopulations and cell‐mediated cytotoxicity (CMI) were studied during radiation therapy in 16 patients with ovarian carcinoma. The total lymphocyte count became depressed in all patients. The depression was more marked among T cells, while the proportion of B cells remained unaffected. In patients with Stage I and II ovarian cancer, CMI was depressed significantly by radiotherapy after 7 days of treatment, remained low at 14 days but recovered despite continuation of radiation. This depression of CMI occurred at a delivered dose of 1,000 rads with subsequent recovery. Patients with Stage III ovarian cancer given pelvic and abdominal radiation were found to have no consistent depression of CMI, a finding similar to that in Stage III ovarian carcinoma patients given chemotherapy.

Mediastinal irradiation in combined modality therapy for hodgkin's disease

Patients with Hodgkins disease who present with large mediastinal masses in the setting of either early or advanced stage disease are frequently treated with combined modality therapy. Policies for radiation dose to the mediastinum in these settings range from no radiation to doses in the 3600-4000 cGy range. We reviewed the charts of 50 patients treated with radiation therapy following remission induction with chemotherapy between 1979 and 1983 to determine whether the dose of radiation to the mediastinum could be correlated with mediastinal control, relapse-free, and overall survival. Patients were divided into groups with small (SM, 30 pts.) and large (LM, 20 pts.) mediastinal masses and analyzed according to whether they had received low dose (LD, less than or equal to 2500 cGy) or high dose (HD, greater than 2500 cGy) radiation to the mediastinum. The 5-year relapse-free survival (RFS) for all 50 patients was 84% (+/- 8%, 95% confidence limits). For the patients with small mediastinal masses, 5-year RFS was 81% +/- 20%, and for the patients with large mediastinal masses, 89% +/- 16%. No clear dose-response effect was observed when the outcomes of the low dose and high dose patients were compared. This was true even in the patients with large mediastinal masses although the high dose subset of this group included patients felt to be at a higher risk for relapse following chemotherapy. Nine of eleven patients with large mediastinal masses treated with chemotherapy and low dose radiation remain disease-free. There was only one isolated mediastinal relapse in the entire group of patients. Treatment was well tolerated with no acute treatment-related deaths. Two patients developed second malignancies. We conclude that combined modality therapy using low dose radiation results in excellent 5-year relapse-free survival for most small and many large mediastinal mass patients, and that it is not necessary to treat all chemotherapy patients who present with mediastinal disease with high dose radiation to achieve these relapse-free survival rates.

Testicular Tumors in 2 Families

Testicular cancers in closely related family members are rare. We herein report the second incidence of pure seminoma occurring in a father and son. The increased risk of malignant tumors developing in the undescended testis is well established. We also describe the second reported incidence of testicular cancers occurring in 2 non-twin brothers, in which 1 of the cancers developed in an undescended testis.