Sparing of the hippocampus and limbic circuit during whole brain radiation therapy: A dosimetric study using helical tomotherapy.

INTRODUCTION: The study aims to assess the feasibility of dosimetrically sparing the limbic circuit during whole brain radiation therapy (WBRT) and prophylactic cranial irradiation (PCI). METHODS AND MATERIALS: We contoured the brain/brainstem on fused MRI and CT as the target volume (PTV) in 11 patients, excluding the hippocampus and the rest of the limbic circuit, which were considered organs at risk (OARs). PCI and WBRT helical tomotherapy plans were prepared for each patient with a 1.0-cm field width, pitch = 0.285, initial modulation factor = 2.5. We attempted to spare the hippocampus and the rest of the limbic circuit while treating the rest of the brain to 30 Gy in 15 fractions (PCI) or 35 Gy in 14 fractions (WBRT) with V(100) >or= 95%. The quality of the plans was assessed by calculating mean dose and equivalent uniform dose (EUD) for OARs and the % volume of the PTV receiving the prescribed dose, V(100). RESULTS: In the PCI plans, mean doses/EUD were: hippocampus 12.5 Gy/14.23 Gy, rest of limbic circuit 17.0 Gy/19.02 Gy. In the WBRT plans, mean doses/EUD were: hippocampus 14.3 Gy/16.07 Gy, rest of limbic circuit 17.9 Gy/20.74 Gy. The mean V(100) for the rest of the brain (PTV) were 94.7% (PCI) and 95.1% (WBRT). Mean PCI and WBRT treatment times were essentially identical (mean 15.23 min, range 14.27-17.5). CONCLUSIONS: It is dosimetrically feasible to spare the hippocampus and the rest of the limbic circuit using helical tomotherapy while treating the rest of the brain to full dose.

Phase II study of hyperfractionated radiotherapy and concurrent weekly alternating chemotherapy in limited-stage small cell lung cancer.

Despite recent advances in combined modality therapy, long-term survival remains elusive in most patients with limited-stage small cell lung cancer (SCLC). The present study was designed to evaluate the activity and toxicity of concurrent hyperfractionated radiotherapy and weekly, alternating-regimen chemotherapy. Twelve patients with limited-stage SCLC and performance status 0-1 were treated with cyclophosphamide 250 mg/m2, etoposide 100 mg/m2, and cisplatin 50 mg/m2 on day 1 every other week, and vincristine 1 mg/m2 on day 8, and ifosfamide 1.2 mg/m2 on days 8 and 9 every other week. Hyperfractionated thoracic radiotherapy, consisting of three daily doses of 1.1 Gy for 20 days to a total dose of 66 Gy, was started on day 1 of chemotherapy. Ten patients (83%) exhibited an objective response (9 CRs and 1 PR) with a median duration of response of 8.6 months. Two complete responders died at 50 and 53 months without evidence of progression and two remain alive and free of SCLC at 73 and 87 months. Median survival was 19.8 months with 2- and 5-year survival rates of 50 and 17%, respectively. Severe toxicity, including grade 3-4 esophagitis (67%) and granulocytopenia (83%), as well as debilitating fatigue and pneumonitis, prompted early termination of the trial. Hyperfractionated radiotherapy and concurrent weekly alternating-regimen chemotherapy resulted in promising response and survival rates, but induced excessive toxicity, in patients with limited-stage SCLC.

Phase I/II study of treatment of locally advanced (T3/T4) non-oat cell lung cancer with concomitant boost radiotherapy by the Radiation Therapy Oncology Group (RTOG 83-12): long-term results.

PURPOSE: This pilot study was undertaken to evaluate the effect of high dose-per-fraction radiotherapy given to the tumor primary concurrently with conventional fractionated radiotherapy to the electively irradiated regional lymph nodes (concomitant boost). This article reports the late results of toxicity and survival. METHODS AND MATERIALS: Fifty-nine patients with histologically proven clinical Stage T3-T4, N1-3 nonsmall cell lung cancer were prospectively enrolled in this study. Fifty-six were evaluable for late effects. The treatment delivered 2.68 Gy daily to the primary tumor, 5 days a week, to a total dose of 75 Gy in 28 fractions in 5.5 weeks. At the same treatment sessions, the electively irradiated nodal areas received 1.8 Gy daily, 5 days per week, to a total dose of 50.4 Gy. All doses were calculated with heterogeneity corrections for lung density. RESULTS: Presently, one patient remains alive at 7.7 years. Median survival was 10.0 months with 1-, 2-, 3-, and 5-year survival rates of 41%, 25%, 18%, and 4%, respectively. Three patients developed severe late complications, including pulmonary fibrosis and osteonecrosis. The remainder of the patients, however, developed only grade 1 or 2 pulmonary fibrosis and/or pneumonitis. CONCLUSION: We conclude that concomitant boost radiotherapy in the manner reported resulted in acceptable late toxicity. The 2- and 3-year survivals compared favorably with the best-reported results in the literature with either hyperfractionated or chemoradiotherapy treatment. Studies that deliver higher radiotherapy doses to the gross tumor combined with chemotherapy are in order.

Chemoradiotherapy of esophageal carcinoma.

BACKGROUND: Chemoradiotherapy has demonstrated efficacy in esophageal cancer but rarely is curative. To improve local control and decrease metastases, a 7-month regimen was used with standard-dose radiotherapy (RT), cisplatin (DDP), and continuous infusion (CI) 5-fluorouracil (5-FU) in patients with locoregional squamous/adenocarcinoma of the esophagus. METHODS: Initial treatment consisted of RT to the esophagus (4000-5000 cGy) for 5-6 weeks, CI 5-FU (300 mg/m2/day) concurrent with RT, and DDP (25 mg/m2/day x 3) for Days 1-3 and 21-23. Two monthly cycles of DDP (75 mg/m2 Day 1) and 5-FU (300 mg/m2 x 21 days) followed. Patients were restaged with endoscopy and computed tomography scan. Patients without evidence of residual disease received three more cycles of chemotherapy (CT); those with persistent tumor underwent esophagectomy or additional CT/RT, and those with disease progression were offered alternative CT. RESULTS: From December 1987 to September 1991, 18 men and 8 women, including 2 with adenocarcinoma, were eligible for inclusion in the study. All were evaluable for toxicity and response. The median age was 61.5 years (range, 50-80 years), the median pretreatment weight loss was 9 lbs, and the median serum albumin level was 4.3 mg%. Therapy was toxic; 19 patients were hospitalized for treatment-related esophagitis, thrombosis, or infection. Grade III and IV leucopenia were seen in 12 patients and 1 patient, respectively. One patient had Grade IV thrombocytopenia. Of 26 patients, 17 (65%) had no tumor on restaging. Five patients had recurrences in the esophagus (1), liver (3), and lung (2). Three patients had second neoplasms. The median survival was 24 months. CONCLUSION: This treatment regimen provides high frequency of local tumor resolution, but with significant toxicity.

Practical aspects of transmission cord blocks in radiotherapy.

We present the advantages of using partial transmission cord blocks throughout treatment, as opposed to adding full-thickness blocks near the end. Such blocks reduce the risk of block omission or mispositioning and require less total time for construction. We also present an argument for the existence of an optimal width for cord blocks used in mediastinal treatments. A figure of merit has been derived which quantifies the tradeoff between narrow blocks, which increase the variation in dose across the block shadow and the risk of positioning errors, and wide blocks, which may unnecessarily shield potential tumor sites. For 60Co, 4- and 10-MV beams, the figure of merit peaks at block widths of 2.0-2.5 cm at the level of the cord. Effective transmission data for cord blocks constructed of cerrobend are given for those three beams. Quality assurance studies show that transmission through cerrobend blocks can be controlled to the required precision.

Cisplatin and etoposide before definitive radiation therapy for inoperable squamous carcinoma, adenocarcinoma, and large cell carcinoma of the lung: a phase I-II study of the Radiation Therapy Oncology Group.

A trial of "neoadjuvant" cisplatin-etoposide and radiation therapy was conducted by the Radiation Therapy Oncology Group for non-small cell carcinoma of the lung limited to the thorax. Thirty evaluable patients were studied: two achieved complete response and four achieved partial response after chemotherapy. All patients underwent radiation therapy as planned, with no unusual acute reactions. Sixteen patients had local failure, and 13 had distant metastasis. Twenty-seven patients are dead, two are alive with cancer, and one is clinically free of cancer at 145 weeks. Five of six patients who survived greater than or equal to 2 years after treatment had adenocarcinomas. There was no unexpected late toxicity. This combination of chemotherapy and radiotherapy is unlikely to improve results in the treatment of inoperable non-small cell carcinoma of the lung over those with radiotherapy alone.

Transmission blocks: clinical and biological rationales.

This paper describes the clinical and biological rationales for the use of transmission blocks. Clinical advantages over the use of full-thickness blocks applied part way through the course of therapy include the use of only one set of fields, blocks, and beam calculations, and less complex chart recording. There is a net saving in time required for the preparation and treatment of the patient. There is also a quality assurance advantage since the impact of a potential error in block positioning is reduced. In terms of biological advantages, it is demonstrated that the linear-quadratic iso-effect model can be applied to predict an improvement of up to 10% in the therapeutic ratio if transmission blocks are used instead of full-thickness blocks.

Dosimetry of rotational photon fields with gravity-oriented eye blocks.

Evolving radiotherapeutic technique is aimed at routine use of an eye protection accessory with uniformity of dose to facial tumors. Rotational 4 MV photon fields with gravity-oriented eye blocks are described in applications to patients and a phantom. A machine-oriented compensator with a slit and beveled edges at eye levels has been applied to increase uniformity of dose over the entire target, including partly blocked regions. Treatment planning parameters are derived from simple geometric relationships. Dose distributions and average tissue-air ratios (TAR) are calculated with a conventional radiotherapeutic treatment planning system, and measured during initial treatments via thermoluminescent dosemeters (TLD) in facial cavities. Machine monitor units of initial treatments (MU1) are calculated from prescribed dose D, TAR, percentage isodose lines, dose rates in air, and compensator transmission; for subsequent treatments, MU1 are modified using averages of unblocked target doses D measured during initial treatment: MU2 = (D/D)MU1. Doses measured on patients' eyelids have been 10 to 15% of prescribed dose. Three dimensional dose distributions were determined using TLD in an anthropomorphic phantom. With beam compensation, eye doses were 15% of unblocked target doses, doses to partly blocked target were 86 to 129% of unblocked target doses, and doses to unblocked target showed 5% mean standard deviations. In vivo and in phantom data were consistent with computer-calculated distributions. For uniformity of target dose, eye-sparing, and simplicity of irradiating tumors surrounding the eyes, the technique investigated compares favorably with conventional techniques.

Hyperthermia in cancer treatment: current and future prospects.

The renewed interest in the possible use of localized hyperthermia in cancer therapy is prompted by two major realizations. The first is the radiobiological evidence indicating that there may be a significant advantage in the use of heat alone or combined with radiation therapy or chemotherapy to enhance the inactivation of tumor cells The second is that early clinical investigation with refractory malignant tumors at temperatures between 41 degrees C and 45 degrees C have shown tumor regression response rate over 70% without increasing normal tissue complication. A phase I/II study using electromagnetic hyperthermia immediately following administration of ionizing radiation was begun at Duke in the fall of 1976 to evaluate the response of normal tissues, the regression of cutaneous and subcutaneous tumors, and the feasibility of such combined modalities in therapeutic radiology. Each hyperthermia session consisted of 45 minutes at 42-43.5 degrees C 2-3 times per week immediately following radiotherapy. The radiation therapy fraction size was usually 2-3 Gy 3-5 times per week with a maximum total of 48 Gy. The 60+ patients treated to date have had squamous cell carcinoma, adenocarcinoma, malignant melanoma, plasmacytoma, liposarcoma, epithelioid sarcoma, and undifferentiated carcinoma. After more than 600 hyperthermia sessions, we have found: (1) local hyperthermia with microwave alone or in combination with ionizing radiation can be used with excellent normal tissue tolerance provided local tissue temperatures are carefully monitored and controlled; (2) a significantly higher level of preferential heat induction into tumor tissue is possible as compared to surrounding normal tissues; (3) repeated hyperthermia at 42-43.5 degrees C for 45 minutes per session immediately following radiation therapy yields favorable therapeutic results. Tumor regression response rate of over 70% was achieved without concomitant increase of normal tissue complication. Therefore, the potentially significant impact on clinical cancer therapy, whether of curative or palliative intent, by moderate thermotherapy is evident. Technical advances to optimize such treatment methods including R & D for delivering a known localized quantity of heat to tumors in any location in the body are expected to progress rapidly. The methods with most promising potential for inducing local thermotherapy are those involving the use of electromagnetic waves, e.g., radiofrequency energy, microwave energy, and ultrasound energy.