Stanley E. Order

Improvement in Quality of Survival Following Whole-Brain Irradiation for Brain Metastasis

The benefits of palliative therapy for patients with brain metastases have often been questioned (1–4) since these patients usually have widely disseminated disease and a limited survival. Assessment of therapeutic gain or successful palliation has proved to be the most difficult task. Prolongation of life (2, 5), or “increased survival for at least six months without further disability” (3), has been the surgical criterion for success, and amelioration of signs was reported as the criterion in the largest radiotherapeutic series (6). Yet, ultimately, it is the improvement of the functional capacity of the patient, his regained intellectual awareness and physical abilities, that determines whether a palliative result has been achieved. It is the purpose of this study to review the clinical findings, results, and implications of the treatment of brain metastases in 108 patients treated with whole-brain radiation. A patient classification based on functional status, which defines improvement and reports suc...

Palliation of hepatic metastasis

Between 1971 and 1975,55 patients underwent palliative radiation therapy for symptomatic hepatic metastasis. Most patients received 2400 rad in 300 rad fractions to the entire liver. There were 31 patients who received concomitant chemotherapy, and 14 who were prior chemotherapy failures. Ninety percent of the patients with symptomatic pain and liver enlargment and significant palliation of their symptoms. The median survival of the entire group was 4.5 months, while those patients experiencing an excellent response (21) had a median survival of 9 months. The median survival of patients having an excellent response to radiation is comparable to that of patients having regional arterial chemotherapy while incuring fewer complications. The overall complication rate of those patients completing therapy (50) was 12%.

Hodgkin's disease: evidence for a tumor-associated antigen.

Abstract Perisplenic nodes and splenic tumor nodules were obtained from two patients with Hodgkins disease and used to immunize individually assigned rabbits. After immunization, the antiserums were absorbed with the normal splenic tissue from the same patient. The absorbed antiserums were used to identify a tumor-associated antigen by indirect immunofluorescence in cryostat sections. Tumor nodules fluoresced, whereas adjacent normal splenic tissue, serving as concomitant control, did not. Common antigenicity between patients was also demonstrated by fluorescence of absorbed antiserums cross-reactive with cryostat sections of other patients tumors.

An aggressive approach to marginally resectable lung cancer.

Between July 1968 and December 1974, 53 patients with lung cancer were planned for preoperative irradiation and surgery. All patients were considered clinically marginally resectable because of advanced local disease, 4 Stage II patients, with limited pulmonary reserve and 49 Stage III patients. Most patients received 3000 to 4000 rad followed in two weeks by thoracotomy. Forty‐six patients were explored and 38 were resectable. Twelve patients are alive with a median follow‐up of 48 months. The cumulative 5‐year survival of all resectable patients is 27%. The survival of patients with marginally resectable lung cancer treated by accelerated radiotherapy followed by aggressive surgery approaches the survival experience of patients with primary resectable lung cancer and is superior to such patients treated with radiation therapy alone.

Immunotherapy of ovarian carcinoma. An experimental model.

The specificity of a tumor antigen of an experimental ovarian carcinoma was determined by immunofluorescence, cytotoxicity, and immunoelectro‐phoresis using an absorbed heterologous tumor antiserum. Tumor controls and normal rabbit sera controls were compared to tumor antiserum‐treated recipients. Tumor control animals died by the 36th day after tumor transplantation. Normal rabbit serum was shown to contain a natural antibody which prolonged survival. Treatment with unabsorbed tumor antiserum in vitro led to 100% survival; 24 hours after tumor transplantation 30–40% survival; 48 hours after tumor transplantation 50%; and when animals with advanced disease were treated from the 4th‐8th day with daily injections this resulted in 30% long‐term survivors. The intraperitoneal administration of tumor antiserum allows for direct binding with tumor cells without dilution in the circulation and at a reduced risk of nonspecific binding in critical organs and demonstrates the efficacy of serologic immunotherapy.

A phase I/II study of the hypoxic cell sensitizer misonidazole as an adjunct to high fractional dose radiotherapy in patients with unresectable squamous cell carcinoma of the head and neck: A RTOG randomized study (#79-04)

A randomized prospective trial was performed to study the toxicity and efficacy of the hypoxic cell sensitizer, misonidazole (MISO), used as an adjunct to high fractional dose radiotherapy in the management of unresectable Stage III and IV squamous cell carcinomas of the oral cavity, oropharynx and hypopharynx. From June 1979 to February 1983, 42 patients were randomized with 40 patients available for analysis. In the radiotherapy (RT) only group, 19 patients received a short course of high fractional dose radiotherapy with 400 rad per day, 5 days per week, to a total of 4400 to 5200 rad. In the radiotherapy plus misonidazole group (RT + MISO) 21 patients received the same radiotherapy plus 1.5 gm/m2 of misonidazole 3 times a week for a total of 7 doses. The observed side effects associated with misonidazole were: persistent numbness and paresthesia (1 patient), transient peripheral nerve paresis and persistent paresthesia (1 patient), and nausea and vomiting (2 patients). The treatment related morbidities were similar in both groups. Acute mucositis was seen in 4 of 19 patients in the RT group and 3 of 21 patients in the RT + MISO group. Acute airway obstruction requiring tracheotomy was seen in 2 patients with massive tumor in the base of tongue (1 in each group). Severe dysphagia requiring NG tube feeding was seen in 3 patients in the RT + MISO group and 3 patients in the RT group. The initial complete response rate in the RT group was 53%, versus 48% in the RT + MISO group. The estimated 2-year loco-regional control rates were 10% for RT alone and 17% for RT + MISO (no significancy). These results indicate that the addition of misonidazole does not improve the efficacy of high fractional dose radiotherapy for management of unresectable head and neck carcinomas. However, high fractional dose radiotherapy can be administered for the management of advanced head and neck carcinomas with acceptable morbidity and thus, is a useful regimen for future clinical trials of hyperbaric oxygen or new hypoxic cell sensitizers.

Computed tomography assisted volumetric analysis of primary liver tumor as a measure of response to therapy

SERIAL COMPUTED TOMOGRAPHY ASSISTED VOLUMETRIC ANALYSES were made in 33 patients with hepatoma. Thirteen of 27 patients with tumor volumes less than 2,290 cc had a partial response to experimental therapy. However, only three of these patients also demonstrated a significant change in liver volume. Tumor volume determinations made by the method described are an accurate (× 10%) and reproducible way to measure response to therapy. In spite of small changes in total liver volume, there may be concomitantly substantial changes in tumor volume.

Selective tumor irradiation by infusional brachytherapy in nonresectable pancreatic cancer: A phase I study

PURPOSEnSelective high-dose radiation of solid tumors has been a goal of radiation oncology. The physiological barriers of solid tumors (high interstitial tumor pressure, reduced tumor vascularity, and poor perfusion) have been major barriers in achieving significant tumor dose of systemically infused radioconjugates. Direct tumor infusional brachytherapy overcomes these barriers and leads to selective high tumor doses.nnnMETHODS AND MATERIALSnThe development of interstitial tumor infusion of macroaggregated albumin (MAA) followed by colloidal chromic phosphate 32P has overcome solid tumor obstacles in 47 patients with nonresectable pancreatic cancer in a Phase I dose escalation study. The colloidal 32P infusion was followed by external radiation and five fluorouracil.nnnRESULTSnOf the 28 patients with cancer limited to the pancreas, 15 of 16 patients retained 86-100% (mean 96%) of the infused colloidal 32P isotope. While the other 12 patients had partial shunting to the liver, shunting to the liver was due to high interstitial resistance with tumor dose deposition of 17-88% (mean 52 %). Of the 19 patients with metastatic pancreas cancer, colloidal 32P tumor deposition ranged from 22 to 100% of the infused dose (mean 79%). The less than optimal tumor deposition led to our increasing the MAA from 600,000 to 1.5-2.5 million particles. Interstitial dexamethasone 2 mg and later 4 mg was infused first and prevented liver shunting by somehow reducing tumor resistance. The median survival in 28 Phase I patients with nonresectable pancreas cancer without metastasis, was 12 months. No significant toxicity occurred when treatment was limited to two infusions with as much as 30 mCi each. The maximum tumor dose was 17,000 Gy (1.700,000 cGy). In 19 nonresectable pancreatic cancer patients with metastasis, a 6.9 months median survival was observed.nnnCONCLUSIONSnInfusional brachytherapy is an outpatient procedure that delivers high-dose radiation selectively to pancreatic cancer. Results of the Phase I study in nonresectable pancreas cancer has led to a national multiinstitutional Phase II trial.

Remission and survival following monthly intraarterial cisplatinum in nonresectable hepatoma.

Precis: Intraarterial delivery of 50 mg/m2 cisplatinum on a monthly basis is a well-tolerated regimen for patients with nonresectable hepatoma. The selective uptake of cisplatinum delivered intraarterially suggests other selective intraarterial protocols would be of use in regional cancers treated with cisplatinum. Background: Sixty-seven patients with nonresectable hepatoma were treated with hepatic artery infusions (HAI) of 50 mg/m2 cisplatinum on a monthly basis. Methods: Forty-eight patients received an initial course of whole liver external radiation with intravenous (IV) cisplatinum 50 mg/m2. Nineteen patients did not receive radiation and received HAI cisplatinum only. All patients then received HAI cisplatinum at 50 mg/m2 on a monthly basis. Six patients were given a tracer dose of radioactive 195mcisplatinum for quantitation by the HAI and IV routes. Results: Monthly HAI cisplatinum was well tolerated and could be repeated indefinitely. Median survival for primarily treated nonresectable hepatomas was 12 months [alpha fetoprotein (AFP) elevated] and 17.5 months (AFP negative). Radioactive cisplatinum given by HAI yielded 34–55% tumor uptake of cisplatinum vs. <5% by IV delivery. Conclusions: Hepatic intraarterial cisplatinum at 50 mg/m2 is a well-tolerated monthly regimen for patients with nonresectable hepatoma.

Radionuclide immunoglobulin lymphangiography: A case report†

Iodine‐131‐labeled immunospecific gamma globulin derived from immunization of rabbits with F antigen, a tumor associated antigen in Hodgkins disease, has been utilized for intralymphatic infusion in a patient with known recurrent Hodgkins disease in the inguinofemoral and pelvic regions. Rectilinear scanning successfully delineated the tumor masses, and external monitoring showed retention of activity in the tumor sites over an 8‐day period.