The impact of radiation dose in combined external beam and intraluminal Ir-192 brachytherapy for bile duct cancer.

PURPOSE: To examine the impact of radiation dose on both survival and morbidity in combined modality treatment of bile duct cancer. METHODS AND MATERIALS: Forty-eight patients with cancer of the extrahepatic bile ducts were treated at Thomas Jefferson University Hospital from 1984-1990. Twenty-four patients received radiation as part of a combined modality approach using external beam radiation, brachytherapy implant and chemotherapy. Twenty-four patients received no radiation in the course of their treatment. Radiation was delivered via high energy photons at standard fractionation, 5 days/week, for an average of 46 Gy. The implant used Ir-192 ribbon sources (average activity was 29 mCi, active length was 6 cm) for a mean dose of 25 Gy at 1 cm. Chemotherapy consisted of 5-FU alone or combined with adriamycin or mitomycin-C. RESULTS: Two-year survival for all 48 patients was 18% (median 9 months). Patients treated with radiation had a 2-year survival of 30% (median 12 months) vs. the no-radiation group, 17% (5.5 months, median), p = 0.01. Those treated to > 55 Gy experienced an extended 2-year survival of 48% (24 months, median), vs. those receiving < 55 Gy, 0% (6 months, median), p = 0.0003. This benefit was also seen when patients were stratified by T-stage. A dose response is further suggested by a lengthening of the median survival with increasing radiation dose (4.5 months, 9 months, 18 months and 25 months for < 45 Gy, 45-55, 55-65, 66-70 Gy, respectively). Neither surgical resection nor chemotherapy produced statistically significant benefits as independent variables. Complications due to radiation occurred in only one patient. CONCLUSION: A dose response is shown with more than double the 2-year and median survival for doses > 55 Gy. A brachytherapy dose of 25 Gy, plus 44-46 Gy external beam is well tolerated. High dose combined brachytherapy and external beam radiation (60-75 Gy) appears to be the most effective modality for extrahepatic bile duct cancer.

Response of the microtubular cytoskeleton following hyperthermia as a prognostic indicator of survival of Chinese hamster ovary cells.

PURPOSE: The response of the microtubular (MT) cytoskeleton to hyperthermia was assessed as a prognostic indicator of cytotoxicity. METHODS AND MATERIALS: Heat-induced collapse and subsequent recovery of the MT system were compared with survival for both nonthermotolerant (NT) and thermotolerant (TT) G1 populations of Chinese hamster ovary (CHO) cells. The response of the MT system was monitored using immunofluorescence staining. The G1 populations of NT and TT cells were heated by submersion in 45.0 and 43.0 degrees C waterbaths. RESULTS: Heat-induced perinuclear collapse of the MT system did not correlate with survival for the NT and TT populations. However, recovery of the organization of the MT cytoskeleton was correlatable with survival. The regression line of survival plotted as a function of MT recovery is fit by: y = -0.43 + 1.03x, r2 = 0.95 (p < 0.0005). CONCLUSION: Restoration of the organization of the MT cytoskeleton following hyperthermia may be used as a prognostic indicator of survival of CHO cells heated in G1.

The medical and economic impact of closed cervical spine dislocations.

The current study examined the medical and economic impact of various treatment modalities of unstable cervical spine dislocations. Thirty-five patients with dislocations of the cervical spine were reviewed retrospectively from two large university hospitals. There were 23 unilateral and 12 bilateral facet dislocations. Fourteen patients were treated nonoperatively and 21 patients were treated with early surgery. Nine of the 14 patients treated nonoperatively redisplaced their dislocations while in an orthosis and required late surgery. Analysis of variance shows that it is the amount of injury (unilateral versus bilateral) that results in statistically significant difference in the injury severity score, Glasgow coma scale, trauma motor index, and the number of complications. Of the treatment groups (operative versus nonoperative), the operative group showed a statistically significant difference in the length of hospital stay. Also noted in the operative group was less traction time, earlier erect physical therapy, an average financial savings of $18,407.00, and equal morbidity or mortality to the nonoperative treatment group. Based on this limited experience, it would appear that "diagnosis related groups" are not capable of supporting traumatic spinal care and, if adopted by other states and third party payers, the concept of trauma and/or spinal cord injury centers may be in jeopardy.

Cholangiocarcinoma: clinical significance of tumor location along the extrahepatic bile duct.

PURPOSE: To define the criteria for resection and/or radiation therapy (RT) of extrahepatic bile duct cancer. MATERIALS AND METHODS: Of 81 patients with extrahepatic bile duct cancer treated from 1983 to 1992, those with proximal duct lesions (n = 56) underwent RT and/or resection or palliative care, and those with distal lesions (n = 25) underwent resection with or without RT. Follow-up was available 3-114 months (median, 28 months). RESULTS: Patients with distal bile duct cancer lived longer than patients with proximal bile duct cancer (survival with Kaplan-Meier analysis, 53% vs 13% at 5 years, respectively, P < .01). Median survival in patients with proximal cancer after RT was more than double that without RT (17 months vs 6 months, respectively, regardless of stage [P = .01]); survival was not significantly different after resection. In patients with distal cancer, RT after resection made no significant difference in median survival (68 months). CONCLUSION: Patients with proximal cancer should undergo primary RT, and expectations should be limited. Patients with distal cancer should undergo resection, and RT may not be needed.

Elapsed radiation therapy treatment time as a predictor of survival in patients with advanced head and neck cancer who receive chemotherapy and radiation therapy.

PURPOSE: To determine whether elapsed radiation therapy treatment time relates to survival in patients with head and neck cancer treated sequentially with chemotherapy and radiation therapy. MATERIALS AND METHODS: From 1981 to 1988, 76 adult patients with bulky stage II-IV head and neck cancer received induction chemotherapy (fluorouracil and cisplatin). Those with a complete or partial response (n = 46) received full-dose definitive radiation therapy (range, 64.0-77.5 Gy; median, 70 Gy). Those with less than a partial response (n = 21) underwent surgery and postoperative radiation therapy (n = 15), palliative radiation therapy (n = 4), or palliative chemotherapy (n = 2). Nine patients refused to undergo radiation therapy after induction chemotherapy. RESULTS: The 5-year overall survival rates were as follows: 32% in all patients, 38% in patients who underwent chemotherapy and radiation therapy, and 27% in patients who underwent chemotherapy, surgery, and radiation therapy. The number of days between radiation therapy treatments was highly predictive of overall survival. In the groups with treatments less than 55 days apart, 56-65 days apart, and more than 66 days apart, the 5-year survival rates were 56%, 46%, and 15%, respectively (P = .02). CONCLUSION: The time between radiation therapy treatments is strongly predictive of survival in patients undergoing sequential chemotherapy and radiation therapy. The use of induction chemotherapy does not negate the need to avoid treatment interruptions during definitive radiation therapy.

Malignant biliary duct obstruction: long-term experience with Gianturco stents and combined-modality radiation therapy.

PURPOSE: To evaluate the effect of combined-modality therapy including intraluminal iridium-192 on stent patency and survival in patients with malignant biliary obstruction treated with Gianturco stents. MATERIALS AND METHODS: Twenty-two patients with unresectable biliary obstruction caused by cholangiocarcinoma (n = 11) or by secondary extrahepatic bile duct malignant tumors (n = 11) were treated with percutaneous biliary drainage followed by intraluminal Ir-192 wire placement (mean dose, 25 Gy) before insertion of Gianturco metal stents. Eleven patients also received external-beam radiation therapy, and 13 patients received chemotherapy. Patency was defined as absence of jaundice or cholangitis that necessitated hospitalization, or as seen on hepatobiliary scans. Survival was determined from the time of stent insertion after brachytherapy. RESULTS: Patients with cholangiocarcinoma had extended mean stent patency of 19.5 months (range, 2-46 months) and mean survival of 22.6 months (range, 2-72 months). Patients with secondary malignant tumors had a mean patency of 4.8 months (range, 1.5-8 months) and a mean survival of 5.3 months (range, 2-9 months). CONCLUSION: Radiation therapy including intraluminal Ir-192 appears to extend stent patency and survival in patients with inoperable cholangiocarcinoma treated with Gianturco metal stents compared with patients with other extrahepatic bile duct malignant diseases and patients treated without combined-modality therapy in other studies.