Donald S. Childs

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.

Neurologic Toxicity Associated with High-Dose Metronidazole Therapy

Excerpt Special interest in hypoxic-cell radiation sensitizers and their potential application in the treatment of malignant tumors has been stimulated by the report of Urtasun and associates (1) o...

Elective whole lung irradiation in the treatment of osteogenic sarcoma

Fifty‐three patients with histologically confirmed osteogenic sarcoma of bone and no clinical evidence of pulmonary metastases were divided into two equivalent groups: one received elective pulmonary irradiation of 1500 rads administered to both lung fields, and the other acted as a control group. There were no significant differences in either survival probabilities or the interval between treatment and the development of pulmonary metastases. Therefore, elective whole lung irradiation so administered was not found to be of value as a prophylactic measure in the treatment of osteogenic sarcoma. There were no recognized untoward reactions to the pulmonary irradiation.

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.

A prospective controlled evaluation of combined pelvic radiotherapy and methanol extraction residue of BCG (MER) for locally unresectable or recurrent rectal carcinoma

Forty-four patients with unresectable primary, residual, or recurrent colorectal carcinoma confined to the pelvis were randomized to treatment with split course megavoltage radiotherapy alone (5,000 rad given over 7 weeks) or in combination with the intradermal administration of the methanol extraction residue of BCG (MER) over an eight-month period. No improvement was observed in frequency of symptomatic palliation, interval to progression, or survival among patients receiving MER. Furthermore, there was no evidence of enhanced immunological status in patients receiving MER as compared to those receiving radiation alone. Although temporary pain relief was seen in 94% of patients with pretreatment pelvic or perineal pain, 37 patients (84%) have experienced subsequent progressive malignant disease. Regional recurrences within the radiotherapy port were observed in 28 of 31 patients who were evaluable for analysis of pattern of sites of initial progression. Eleven of the 28 patients with local failure also had distant metastasis at the time of tumor progression. There was no discernible clinical value associated with MER treatment in combination with radiotherapy as employed in this study. The high frequency of pelvic recurrence following radiotherapy at the dose and schedule we employed highlights the need for more effective treatment strategies for this group of patients.

TREATMENT OF MALIGNANT NEOPLASMS OF THE GASTROINTESTINAL TRACT WITH A COMBINATION OF 5-FLUOROURACIL AND RADIATION: A RANDOMIZED DOUBLE-BLIND STUDY.

Combined chemotherapy and irradiation in the management of malignant disease is a subject of wide and current interest. It has been hoped that the combining of these therapeutic modalities would produce results superior to those achieved with either alone. Hodnett recently reviewed the literature in this field (4). Some authors believe that their results demonstrate marked synergism or additive effects of the combined therapy, while others have withheld judgment, pending the results of controlled studies. The University of Wisconsin group published several reports of controlled studies. They used 5-fluorouracil (5-FU) and irradiation to treat mammary carcinoma of mice (6) and the same combination for bronchogenic carcinoma in man (1, 3). In the animal studies, the combination of 5-fluorouracil, actinomycin P2, or cyclophosphamide (Cytoxan) with fractional x-ray therapy resulted in increased inhibition of tumor growth as well as in prolonged survival when compared to either mode of therapy alone. From thei...

Radiotherapy plus 5-Fu compared to radiotherapy alone for inoperable and unresectable bronchogenic carcinoma

One hundred and eighty‐eight patients with inoperable or unresectable bronthogenic carcinoma, classified by cell type and extent of disease, were randomly allocated to radiotherapy alone or to radiotherapy plus 5‐FU. Results of therapy, evaluated primarily by survival rates, revealed no significant improvement by the addition of 5‐FU. For example, the survival rates at 12 months for patients with squamous cell carcinoma were 32% after radiotherapy alone and 36% after radiotherapy plus 5‐FU. Comparable survival rates for patients with adenocarcinoma were 42% and 60%; for patients with small cell carcinoma, 19% and 23%; and for patients with large cell undifferentiated carcinoma, 31% and 28%. Our data reveal that the regimen of 5‐FU and radiotherapy is not significantly more effective than radiotherapy alone in the treatment of inoperable or unresectable bronchogenic carcinoma.

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.

ADJUVANT USE OF RADIOACTIVE COLLOIDS IN THE TREATMENT OF CARCINOMA OF THE OVARY.

The definitive treatment for malignant lesions of the ovary is removal of the tumor by hysterectomy and bilateral salpingo-oophorectomy. The peritoneal surfaces are a major route of metastasis in ovarian carcinoma (6), and at operation release of malignant cells into the peritoneum by spill from a cystic tumor, the presence of malignant cells in peritoneal washings, and superficial excrescences of tumor on the surface of the ovary are signs that peritoneal spread has already taken place or is highly likely. Such situations have been considered indications for postoperative radiation therapy. Irradiation of the entire peritoneal cavity by conventional external means at cancerocidal dose levels is not possible in most patients, however, because of the large volume of tissue to be treated. The definitive treatment for malignant lesions of the ovary is removal of the tumor by hysterectomy and bilateral salpingo-oophorectomy. The peritoneal surfaces are a major route of metastasis in ovarian carcinoma (6), and...

Radiation therapy and 100 per cent oxygen breathing in the treatment of adenocarcinomas of the large bowel. A controlled study.

The oxygen effect is a well established radiobiologic principle. The exploitation of this effect in clinical radiation therapy has not been particularly rewarding. The work of Cater and Silver (1) and Rubin (2) has indicated, however, that breathing 100 per cent oxygen at atmospheric pressure during conventionally fractionated radiation therapy is worthy of investigation. In 1964, our group undertook a study of patients with adenocarcinoma of the large bowel in whom the lesion was unresectable at the time of operation, or biopsy verified a recurrent tumor. There was no clinical or laboratory evidence of distant metastasis. All known tumor could be encompassed within radiation-therapy portals of 20 × 20 cm or less. All patients were treated with supravoltage radiation therapy at the rate of 1,000 to 1,200 rads in five to six fractions per week to a total midplane dose of 3,750 to 4,500 rads. Composition of the treatment groups was determined by random selection. Onehalf the patients breathed 100 per cent o...