Absence of major depressive disorder in female cancer patients.

This investigation evaluated the prevalence of depression in female patients who had cancer in any of five predesignated sites. Five hundred five women aged 17 to 80 (190 with breast cancer, 143 with gynecologic malignancies, 111 with melanoma, 37 with bowel cancer, and 24 with lymphoma) were randomly screened. Assessment included the Hamilton rating scale for depression, the Zung self-rating depression scale, the Karnofsky performance scale, and a 10-cm visual pain analogue line. The results revealed a mean Hamilton of 10.2 (range, 0 to 41; SD, 7.5), a mean Zung score of 35.3 (range, 11 to 68; SD, 9.6), a Karnofsky median score of 80, and a median pain score of 0. Scores on the Zung scale were highly correlated with those of the Hamilton scale (r = .75). Based on cutoff scores accepted as indicating depression (Hamilton greater than or equal to 20 and Zung greater than or equal to 50), patients were depressed. The depressed subgroup was in significantly more pain, experienced greater physical disability, and was more likely to have had prior episodes of depression as compared to the non-depressed women. The two best predictors of current depression were performance status (Karnofsky) and history of depression. No relationship was found between depression and other demographic variables or disease parameters (diagnosis, time since diagnosis, stage or phase of illness, and current treatment). Our findings indicate that the prevalence of major depression in cancer patients is lower than many previous studies have indicated and falls within the range seen in the general population.

Stage I and II non-Hodgkin's lymphomas: long-term results of radiation therapy.

One hundred and sixteen patients with Stages I and II non-Hodgkin's lymphomas were treated with curative radiotherapy between 1964 and 1977. The initial biopsy material was classified according to the criteria of Rappaport et al. All the patients except six were followed for a minimum of 8 years or until death with ninety-two patients having been followed for 10 or more years. Histological pattern was found to be an important prognostic factor with better survival in patients with nodular histology. There were forty-three patients with an initial involvement of an extra-nodal site forming 37% of the total group. Stage I extra-nodal lymphomas had a survival and recurrence-free survival rates of 80% and 74% respectively, similar to those of nodal lymphomas. Stage II patients in both groups did worse than those with Stage I. Survival rates and disease-free survival rates for different histologic types and their pattern of recurrence are presented.

The influence of surgery and radiation therapy on patients with brain metastases.

The place for operation and for radiation therapy in the management of brain metastases is reviewed from the experience of 1895 patients treated in two studies of the Radiation Therapy Oncology Group. Operative removal may be of benefit to patients with solitary peripheral lesions in non-critical brain locations. Operation is also appropriate when the diagnosis is in doubt. Radiation therapy with appropriate steroid management is of benefit to patients with multiple metastases or where operative intervention is not reasonable. Short course low-dose treatment has been as beneficial as more aggressive prolonged radiation therapy.

Re-irradiation of locally recurrent tumors with fast neutrons.

Forty-six patients with locally recurrent disease were re-irradiated with fast neutrons at Fermilab. All had received prior radical radiation therapy either with or without surgery. Six were palliative. Forty patients treated with curative intent were analyzed for local response, survival, and complications. The overall response rate was 78% (31/40); 50% (20/40) had a complete local response. Ten of 16 patients (63%) with non-epidermoid carcinomas in the head and neck regions had complete response, whereas only nine of twenty patients (45%) with epidermoid carcinomas were complete responders. In a subset of 12 patients with salivary gland type tumors, 10 had a complete response (83%). Two of these 10 patients are alive beyond 5 years. Observed median survival for the forty patients was 9.3 months, and for complete responders 14.4 months. Observed median survival for partial responders was only 7.5 months. Four of six patients treated for palliation had significant subjective improvement. Significant morbidity, Grade III or greater (EORTC/RTOG scale), was seen in only 10 patients (25%), and this was found to depend directly on the total dose delivered. We conclude that neutron beam therapy can be used as a therapeutic modality for patients with recurrent tumors with an acceptable degree of morbidity.

Salvage whole abdomen radiation therapy: its role in ovarian cancer.

PURPOSE: In spite of high initial response rates, many patients with epithelial ovarian carcinoma eventually fail their primary treatment. Further treatment with second-line regimens has been ineffective in producing durable responses. Thus, whole abdomen radiation therapy was evaluated as a salvage therapeutic modality as to its feasibility, efficacy, and toxicity. METHODS AND MATERIALS: Between June 1983 and June 1990, 44 patients who failed one or more chemotherapeutic regimens were treated with whole abdomen radiation therapy. Forty patients had epithelial carcinoma of the ovary and the remaining had primary adenocarcinoma of the peritoneal cavity. Radiation was delivered with an open-field technique and 2500 cGy were planned to the whole abdomen, with a boost when indicated. Prior to radiation, the amount of residual disease after debulking was noted to be microscopic in one-half of the patients and macroscopic in the other half. Pelvis alone was the site of residual disease in 14 patients, and upper abdominal involvement was found in 30. RESULTS: Five patients (11%) were unable to complete the planned therapy secondary to acute toxicity. The 4-year actuarial survival and recurrence-free survival rates for the entire group were 23% and 22%, respectively. The survival and recurrence-free survival rates for the group with microscopic residual disease at 37% and 42% were significantly better than those for the patients with macroscopic residual disease at 9% and 5% (p < 0.005; p < 0.001) at 4 years, respectively. Patients with disease limited to pelvis only had a recurrence-free survival of 56% compared to 0% when the upper abdomen was involved (p < 0.005). The abdomino-pelvic cavity was the first site of recurrence in 28 of 31 patients in whom the site of recurrence could be determined. Eight patients (18%) experienced bowel complications, of whom five needed surgical intervention. CONCLUSIONS: Whole abdomen radiation therapy with a pelvic boost is feasible with acceptable acute and late toxicity. It is effective in patients with minimal residual disease.

Normal tissue reactions and complications following high-energy neutron beam therapy: I. Crude response rates.

The incidence of significant complications (fibrosis, ulceration, necrosis of bone or soft tissue or serious functional impairment) was determined in relation to neutron dosage and follow-up time for 5 anatomical sites totalling 617 patients who had survived 2 or more years following treatment. The regions studied were head and neck (268 patients), thorax (lung and esophagus, 76 patients), upper abdomen (132 patients), pelvis (prostate and bladder, 114 patients) and extremities (27 patients). Neutron doses ranged from 16 to 28 Gy. All patients were followed until death or up to 10 years after treatment. A total of 109 complications were observed yielding a crude complication rate of 18% for the whole series. Observed complication rates were 7% in the 16-20 Gy dose range, 19% between 20 and 24 Gy, and 33% in patients receiving more than 24 Gy. Probit analysis of the data indicated a median effective dose (50% complications) of 29 (+/- 0.5) Gy with an estimated standard deviation of 8 Gy. A reasonable estimate of "tolerance" may then be taken as 29 - 8 = 21 Gy. Comparing the 5 anatomical sites revealed no significant differences in estimated tolerance doses. With the available data, no effect of field-size or target volume could be demonstrated. The incidence of complications apparently increases with time in long-term survivors. Although the overall incidence is only 18%, actuarial analysis of the data suggests that the complication rate might have exceeded 50% if all treated patients had survived 10 years. It is concluded that, with the exception of the nervous system and possibly other viscera, a neutron dose of 20 Gy (in 12 fractions over 4 weeks) represents a practical tolerance limit for all sites.

An update on malignant salivary gland tumors treated with neutrons at Fermilab.

One hundred and thirteen cases of recurrent and/or unresectable malignant salivary gland tumors, treated with fast neutron therapy at Fermilab between September 1976 and December 1984, are analyzed for local control, sites of failure, and treatment-related morbidity. Sixty-three patients had major and 55 had minor salivary gland tumors. Local control was achieved in 67% of patients with major and 58% of patients with minor salivary gland tumors. In the subgroup of patients with oropharyngeal and oral cavity lesions, 19/24 (80%) had local control. However, only four of 15 patients with maxillary antrum tumors had successful control of their disease. Seventy-four percent of patients with lesions measuring 5 cm or less and 30% of patients with larger lesions had their local disease controlled. Histology did not influence the local control rate. Both observed and adjusted median survival for patients with major salivary gland tumors was 36 months. Disease-free survival was 31 months. Observed and adjusted median survivals for patients with minor salivary gland tumors are 48 and 57 months respectively. Twenty of 86 patients (23%) had major morbidity; this was directly related to the total dose delivered. In the dose range 20-24 Gy the complication rate was 16%. Most of these complications were successfully managed with minimal functional disability. We have concluded that fast neutron irradiation is an appropriate treatment for malignant salivary gland tumors.

Failure of accelerated neutron therapy to control high grade astrocytomas.

Sixty-two patients with high grade malignant astrocytoma were treated with fast neutrons using three different treatment schemes to evaluate the effect of shortening the overall time. Dose and fraction number were kept constant. The total dose was 16-18 neutron Gy delivered in six fractions, weekly for 6 weeks, twice a week over 3-4 weeks, or three times a week over 2 weeks. There were no obvious differences in survival times among the three groups. We conclude that accelerated neutron therapy does not improve survival of patients with grade 3 and 4 astrocytoma.

Fast neutron beam radiation therapy in the United States.

Following a 30-year hiatus after Dr. Stone's work in the 1930's and 1940's, clinical trials with fast neutrons were restarted in the United States in 1972. Approximately 2500 patients have been treated with neutrons since that time. Three hundred and seven patients with squamous cell carcinomas of the head and neck were entered on an RTOG-coordinated randomized study comparing standard photon irradiation with mixed beam radiation therapy. No significant differences were noted in the local control, survival or complication rates. One hundred and sixty patients were entered on a randomized glioblastoma study. Although there were no significant differences in median survival, autopsy results showed greater tumor effect on the neutron-treated tumors. Twenty-six patients were treated for transitional cell carcinomas of the bladder with either preoperative mixed beam irradiation or mixed beam irradiation alone. Both the local control rates and survival rates compare favorably with photon radiation therapy. The future of fast neutron beam radiation therapy in the United States is discussed.

Technique for breast irradiation using custom blocks conforming to the chest wall contour.

A technique for the treatment of the breast and regional nodes is presented. The technique involves the use of tangential fields to treat the breast and chest wall. Customized blocks which conform to the slope of the chest wall are made for each tangent field. Simulation and treatment with this technique requires no special equipment. The setup is simple and quick. A three-field technique is also described using the custom half-beam blocks; this technique avoids the use of tangential field corner blocks, thus simplifying simulation and treatment.

Retrospective analysis of hyperthermia for use in the palliative treatment of cancer: a multi-modality evaluation.

Forty-two patients with local or superficial metastatic or recurrent malignant tumors were treated in a non-randomized Phase I/II study to assess the tumoricidal effects of heat combined with radiation and/or chemotherapy. Radiation doses administered averaged 3130 +/- 350 cGy; chemotherapeutic agents employed included bleomycin, mitomycin-C, adriamycin, and cis-platin, heat was induced by radiative or interstitial microwave applicators operating at frequencies ranging from 95 to 900 MHz. Forty-one of the forty-two patients were evaluated for initial therapeutic effects yielding the following response distributions: local hyperthermia with radiation--42% complete response (CR), 44% partial response (PR), and 15% no response (NR); local hyperthermia with chemotherapy--0% CR, 50% PR and 50% NR. Long-term response duration was evaluated for local hyperthermia with radiation, yielding mean time to recurrence of 9.4 months for CR's and mean time to progression of 3.4 months for PR's. In retrospective analysis, we examined the correlations of previously established response-predictor variables of tumor volume and minimum thermal dose with both initial and long-term response rates. Initial complete response rates were correlated directly with non-site-specific minimum thermal dose, varied inversely with tumor volume and exhibited a positive correlation for a limited histologic type/treatment site combination. Surprisingly, long-term response did not correlate either with tumor volume or thermal dose. The frequency of thermally induced complications, which did not correlate with any measured thermal parameters, was found to be 42%, expressed on a per-patient basis.

Fast neutron radiation therapy for unresectable squamous cell carcinomas of the head and neck: the results of a randomized RTOG study.

Forty patients with advanced, unresectable squamous cell carcinomas of the head and neck were entered on a prospective, randomized study comparing fast neutron radiation therapy with conventional photon radiation therapy. Twenty-six patients were randomized to neutrons, and 14 patients were randomized to photons. The randomization was purposefully unbalanced in favor of the experimental treatment. The complete response rate for the neutron-treated group of patients was 52%. The complete response rate for the photon-treated group of patients was 17%. The difference is statistically significant at the p = .04 level. The two-year survival rates for the neutron-treated group and the photon-treated group were 25 and 0%, respectively. The major complication rates were not statistically significantly different for the two groups (18% for neutrons, and 33% for photons).

Tolerance of the human spinal cord to high energy p(66)Be(49) neutrons.

The risk of post irradiation myelopathy was evaluated in 76 patients followed for 1-5 years after neutron irradiation of the cervical and thoracic regions. No overt myelopathy was observed. Forty-six patients received doses (central cord dose) in excess of 10 Gy, 9 received doses in excess of 12 Gy, and 5 received doses between 13 and 17 Gy, all without any evidence of spinal cord injury. On careful questioning, a subjective transient neuropathy (a tingling sensation in one extremity) was reported by 6 patients, but this was apparently unrelated to dose. A review of available literature revealed a total of 14 patients with myelopathy, 13 of whom received doses in excess of 13 Gy delivered with relatively low energy neutrons generated by the deuteron + beryllium reaction. It is concluded from these studies that the tolerance limit for the human spinal cord irradiated with high energy [p(66)Be(49)] neutrons is close to 15 Gy, above which the risk of cord injury becomes significant. Central cord doses of 13 Gy or less appear to be well tolerated with little, if any, risk of myelopathy. These conclusions are valid for a treatment time of 4 weeks or more with two or more fractions per week (9 or more fractions). The RBE for the human spinal cord irradiated under the above conditions compared with conventionally fractionated photon therapy does not exceed 4.0.

Carcinoma of the nasopharynx: survival and patterns of recurrence.

We have analyzed survival, disease-free (NED) survival, and patterns of recurrence for 76 patients with carcinoma of the nasopharynx treated from June 1964 through July 1979. Patients with Stages I through IV, who were treated for cure, comprise the study group. Megavoltage teletherapy treatment was delivered to the primary bilateral neck and supraclavicular areas. Dose to the nasopharynx ranged from less than 55 Gy to 70 Gy with several patients receiving higher doses. The observed 5 year NED survival rates were: Stage I, 75%; Stage II, 20%; Stage III, 42%; and Stage IV, 31%. During a 5-year minimum follow-up for all patients, 46 or 60.5% failed. Ninety-five percent of these failures occurred within 3 years; only two patients relapsed after more than 5 years.

Results of radiotherapeutic management of primary carcinoma of the vagina.

Forty-five previously untreated patients with primary carcinoma of the vagina were treated with curative radiotherapy from 1965 through 1985. All patients were staged according to the FIGO system. One patient was classified as Stage 0, 15 as Stage I, 22 as Stage II, 6 as Stage III, and 1 as Stage IV. Treatment consisted of intracavitary irradiation alone in Stage 0 patients. Stage I patients received intracavitary/interstitial irradiation alone or in combination with external irradiation and an implant when feasible. When treated with an implant only, the total tumor dose delivered was between 65-70 Gy. External irradiation consisted of delivering a dose of 45-50 Gy over a period of 4 1/2-5 weeks to the whole pelvis to treat the regional lymph nodes. An additional dose of 20-25 Gy was delivered to the site of original involvement using an implant when feasible. If not technically feasible, as in advanced stages, the patient was treated with additional external irradiation to a total dose of 65-70 Gy by a shrinking field technique. All patients except one were followed either until death or for a minimum of 2 years. The actuarial 5-year survival rates were 100% for Stage 0, 78% for Stage I, and 71% for Stage II patients. None of the patients with Stage III or IV disease survived. Of the patients who recurred, all but two did so within 16 months after diagnosis. Pelvic recurrence as the first site of recurrence occurred in 86% of the patients who recurred. Distant recurrence as a component occurred in 20% of all failures. Complications as a consequence of therapy occurred in 18% of the patients. Vaginal necrosis that healed with conservative treatment was seen in four patients and the other four patients had rectal complications of varying severity. Thus, curative radiotherapy is an effective method of treatment, with acceptable morbidity, in patients with early stage primary carcinoma of the vagina.

Neutron vs photon irradiation of inoperable salivary gland tumors: results of an RTOG-MRC Cooperative Randomized Study.

A total of 32 patients with inoperable, recurrent or unresectable malignant salivary gland tumors were entered on a randomized RTOG/MRC study comparing fast neutron radiotherapy with conventional photon radiotherapy. Twenty-five patients were entered from the United States and 7 patients were entered from Scotland. Seventeen patients were randomized to receive neutrons and 15 patients were randomized to receive photons. Sixty-one percent of the neutron-treated patients and 75% of the photon-treated patients presented with inoperable or unresectable tumors, while 39% of the neutron-treated and 25% of the photon-treated patients had recurrent disease. Twenty-five patients were study-eligible and analyzable. The minimum follow-up time is 2 years. The complete tumor clearance rates at the primary site were 85% (11/13) for neutrons and 33% (4/12) for photons following protocol treatment (p = 0.01). The complete tumor clearance rates in the cervical lymph nodes were 86% (6/7) for neutrons and 25% (1/4) for photons. The overall loco/regional complete tumor response rates were 85% and 33% for neutrons and photons respectively. The loco/regional control rates at 2 years for the 2 groups are 67% for neutrons and 17% for photons (p less than 0.005). The 2-year survival rates are 62% and 25% for neutrons and photons respectively (p = 0.10). These findings are consistent with previously published uncontrolled series.

Preoperative combined modality therapy for stage III M0 non-small cell lung carcinoma.

More than 1/3 of all non-small cell lung carcinoma (NSCLC) patients present with locally advanced non-metastatic disease. Despite radiation therapy and surgery the survival of these patients remains poor. In an effort to improve upon these results 33 clinical Stage III M0 patients from April 1985 through September 1986 were entered into a Phase II study at Rush-Presbyterian-St. Luke's Medical Center. Treatment included 5-FU by continuous infusion, VP-16, cisplatin and concurrent split course radiation therapy followed by surgical resection when possible. The overall clinical response rate is 74%. Fifty-seven percent of the preoperative group of patients went to surgery with a 100% resectability rate. These patients had a 50% pathologic complete response with no tumor found in the resected specimen. All surgical margins were free of disease and there were no operative deaths. This concurrent combined modality therapy is feasible with the major toxicities being leukopenia, nausea, and vomiting. With an overall median follow-up of 15 months, 36% of the patients remain alive. Overall local control is 71%. Actuarial observed 2 yr. survival is 33% and the median survival is 15 months. Histologic complete response appears to be an early indicator of the efficacy of this treatment regime. With 83% of the resected pathologic complete responders alive without evidence of disease, this preoperative combined modality therapy offers an appealing approach.

Neutron irradiation of human pelvic tissues yields a steep dose-response function for late sequelae.

PURPOSE: Analysis of the dose-response function in normal tissues following pelvic irradiation for carcinoma of the prostate. METHODS AND MATERIALS: A homogeneous group of 136 patients with locally advanced carcinoma of the prostate were treated with the Fermilab high-energy neutron beam at three dose levels: 19, 20.4, and 21 Gy, using the same treatment plan and fractionation scheme for all patients. RESULTS: Tumor control rates were about 83% at the three dose levels studied. However, the normal tissue complication rate (late sequelae) varied with dose: 0 out of 5 at 19 Gy, 5 out of 58 (8.6%) at 20.4 Gy, and 9 out of 73 (12.3%) at 21 Gy. CONCLUSIONS: Neutron therapy to the pelvis reveals a steep dose-response function for late effects with a coefficient of variation of only 11%. This is lower than that usually observed with photons or with less uniform clinical data sets, and may be characteristic for well-planned high-LET radiotherapy.

Combined modality therapy for stage III non-small cell lung carcinoma: results of treatment and patterns of failure.

Patients with Stage III non-small cell lung carcinoma continue to pose a therapeutic problem with dismal cure rates. In an effort to improve on these results, 129 patients with biopsy-proven clinical Stage III non-small cell lung carcinoma from November 1982 through November 1987, were entered into two consecutive Phase II studies at Rush-Presbyterian-St. Luke's Medical Center. Treatment in the first study consisted of Cisplatin and 5-Fluorouracil infusion with concomitant split course radiation; in the second Etoposide was added. Radiation and chemotherapy were given simultaneously on days one through five of each cycle in a preoperative fashion for four cycles in patients considered eligible for surgery and in a definitive fashion for six cycles in patients considered ineligible for surgery. Radiation was given in 2 Gy fractions for a planned preoperative dose of 40 Gy and a definitive dose of 60 Gy. Surgical resection was attempted four to five weeks later in patients treated preoperatively. Thus, 83 patients were treated preoperatively and 46 definitively. Eighty-three patients (64%) had IIIA disease and IIIB disease was found in the remainder of the patients. Sixty-two patients (75%) in the eligible for surgery group had a thoracotomy after the combined treatment with a resectability rate of 97% and an operative mortality rate of 5%. There were 17 patients (27%) with no evidence of residual cancer in the resected specimen. Three-year survival for the eligible for surgery group at 40% was significantly better than 19% observed in the ineligible for surgery group (p = 0.003). Seventy-six percent of the patients with no residual cancer in the resected specimen are recurrence-free at three years compared to 34% of the patients with gross residual. A total of 81 patients have failed after their treatment; 49 (59%) in the eligible for surgery group and 32 (70%) in the ineligible for surgery group. Of all the patients who failed, local failure alone and as a component occurred in 21 (26%) and 36 (44%) patients, respectively. Failure in distant sites alone was noted in 56% of the overall failures. Severe toxicity was unusual. There were three treatment related deaths (2%). Radiation esophagitis and pneumonitis were only mild to moderate seen in less than 10% of the patients. Survival rates and patterns of failure according to the stage of the disease, histology, treatment group and pathologic response will be presented in detail.

Mixed neutron/photon irradiation of unresectable squamous cell carcinomas of the head and neck: the final report of a randomized cooperative trial.

Three hundred and twenty-seven patients with inoperable squamous cell carcinomas of the head and neck were entered on a randomized study comparing a mixture of neutron and photon ("mixed beam") radiation therapy with photon/electron radiation therapy. Neutron treatment was delivered with fixed-beam, physics-laboratory-based equipment. Patients with histologically proven tumors of T-stage T2, T3, or T4 and any N-stage were eligible for randomization. Primary tumor sites were limited to cancers originating in the oral cavity, oropharynx, supraglottic larynx, or hypopharynx. Patients entered on this study now have a minimum at-risk follow-up period of 6 years. Study results reveal no significant differences in overall loco-regional tumor control rates or survival. Subgroup analysis reveals significant differences based on whether or not patients presented with positive lymph nodes. Loco-regional tumor control rates for patients presenting with positive lymph nodes were 30% for mixed-beam-treated patients versus 18% for photon-treated patients (p = 0.05). Loco-regional tumor control rates for patients presenting without positive lymph nodes were 64% for photon-treated patients and 33% for mixed-beam-treated patients (p = 0.004). Control of tumor located in the nodal sites favored mixed beam over photons by a margin of 45% (49/109) to 26% (23/87) with a significance of p = 0.004. Possible explanations for these contradictory findings are discussed.