Comparative analyses of linac and Gamma Knife radiosurgery for trigeminal neuralgia treatments.

Dedicated linac-based radiosurgery has been reported for trigeminal neuralgia treatments. In this study, we investigated the dose fall-off characteristics and setup error tolerance of linac-based radiosurgery as compared with standard Gamma Knife radiosurgery. In order to minimize the errors from different treatment planning calculations, consistent imaging registration, dose calculation and dose volume analysis methods were developed and implemented for both Gamma Knife and linac-based treatments. Intra-arc setup errors were incorporated into the treatment planning process of linac-based deliveries. The effects of intra-arc setup errors with increasing number of arcs were studied and benchmarked against Gamma Knife deliveries with and without plugging patterns. Our studies found equivalent dose fall-off properties between Gamma Knife and linac-based radiosurgery given a sufficient number of arcs (>7) and small intra-arc errors (<0.5 mm) were satisfied for linac-based deliveries. Increasing the number of arcs significantly decreased the variations in the dose fall-off curve at the low isodose region (e.g. from 40% to 10%) and also improved dose uniformity at the high isodose region (e.g. from 70% to 90%). As the number of arcs increased, the effects of intra-arc setup errors on the dose fall-off curves decreased. Increasing the number of arcs also reduced the integral dose to the distal normal brain tissues. In conclusion, linac-based radiosurgery produces equivalent dose fall-off characteristics to Gamma Knife radiosurgery with a high number of arcs. However, one must note the increased treatment time for a large number of arcs and isocentre accuracies.

Dosimetric characteristics with spatial fractionation using electron grid therapy.

Recently, promising clinical results have been shown in the delivery of palliative treatments using megavoltage photon grid therapy. However, the use of megavoltage photon grid therapy is limited in the treatment of bulky superficial lesions where critical radiosensitive anatomical structures are present beyond tumor volumes. As a result, spatially fractionated electron grid therapy was investigated in this project. Dose distributions of 1.4-cm-thick cerrobend grid blocks were experimentally determined for electron beams ranging from 6 to 20 MeV. These blocks were designed and fabricated at out institution to fit into a 20 x 20-cm(2) electron cone of a commercially available linear accelerator. Beam profiles and percentage depth dose (PDD) curves were measured in Solid Water phantom material using radiographic film, LiF TLD, and ionometric techniques. Open-field PDD curves were compared with those of single holes grid with diameters of 1.5, 2.0, 2.5, 3.0, and 3.5 cm to find the optimum diameter. A 2.5-cm hole diameter was found to be the optimal size for all electron energies between 6 and 20 MeV. The results indicate peak-to-valley ratios decrease with depth and the largest ratio is found at Dmax. Also, the TLD measurements show that the dose under the blocked regions of the grid ranged from 9.7% to 39% of the dose beneath the grid holes, depending on the measurement location and beam energy.

Cerebellar liponeurocytoma. Case report and review of the literature.

Cerebellar liponeurocytoma is a rare tumor of the posterior fossa that has many morphological similarities to medulloblastoma and neurocytoma. Recently the World Health Organization working group for classification of central nervous system neoplasms adopted the term "cerebellar liponeurocytoma" to provide a unified nomenclature for a tumor variously labeled in the literature as lipomatous medulloblastoma, lipidized medulloblastoma, medullocytoma. neurolipocytoma, lipomatous glioneurocytoma, and lipidized mature neuroectodermal tumor of the cerebellum. The rarity of this tumor and paucity of pertinent information regarding its biological potential and natural history have resulted in the application of various treatment modalities. It is suggested in the available literature that these lesions have a much more favorable prognosis than typical medulloblastomas, and that adjuvant therapy for liponeurocytoma need not be as extensive as that administered for medulloblastomas.

Neurocognitive outcome in brain metastases patients treated with accelerated-fractionation vs. accelerated-hyperfractionated radiotherapy: an analysis from Radiation Therapy Oncology Group Study 91-04.

PURPOSE: To evaluate neurocognitive outcome as measured by the Mini-Mental Status Examination (MMSE) among patients with unresectable brain metastases randomly assigned to accelerated fractionation (AF) vs. accelerated hyperfractionated (AH) whole-brain radiation therapy (WBRT). METHODS AND MATERIALS: The Radiation Therapy Oncology Group (RTOG) accrued 445 patients with unresectable brain metastases to a Phase III comparison of AH (1.6 Gy b.i.d. to 54.4 Gy) vs. AF (3 Gy q.d. to 30 Gy). All had a KPS of >or= 70 and a neurologic function status of 0-2. Three hundred fifty-nine patients had MMSEs performed and were eligible for this analysis. Changes in the MMSE were analyzed according to criteria previously defined in the literature. RESULTS: The median survival was 4.5 months for both arms. The average change in MMSE at 2 and 3 months was a drop of 1.4 and 1.1, respectively, in the AF arm as compared to a drop of 0.7 and 1.3, respectively, in the AH arm (p = NS). Overall, 91 patients at 2 months and 23 patients at 3 months had both follow-up MMSE and computed tomography/magnetic resonance imaging documentation of the status of their brain metastases. When an analysis was performed taking into account control of brain metastases, a significant effect on MMSE was observed with time and associated proportional increase in uncontrolled brain metastases. At 2 months, the average change in MMSE score was a drop of 0.6 for those whose brain metastases were radiologically controlled as compared to a drop of 1.9 for those with uncontrolled brain metastases (p = 0.47). At 3 months, the average change in MMSE score was a drop of 0.5 for those whose brain metastases were radiologically controlled as compared to a drop of 6.3 for those with uncontrolled brain metastases (p = 0.02). CONCLUSION: Use of AH as compared to AF-WBRT was not associated with a significant difference in neurocognitive function as measured by MMSE in this patient population with unresectable brain metastases and limited survival. However, control of brain metastases had a significant impact on MMSE.

Radiosurgery for patients with brain metastases: a multi-institutional analysis, stratified by the RTOG recursive partitioning analysis method.

PURPOSE: To estimate the potential improvement in survival for patients with brain metastases, stratified by the Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) class and treated with radiosurgery (RS) plus whole brain radiotherapy (WBRT). METHODS AND MATERIALS: An analysis of the RS databases of 10 institutions identified patients with brain metastates treated with RS and WBRT. Patients were stratified into 1 of 3 RPA classes. Survival was evaluated using Kaplan-Meier estimates and proportional hazard regression analysis. A comparison of survival by class was carried out with the RTOG results in similar patients receiving WBRT alone. RESULTS: Five hundred two patients were eligible (261 men and 241 women, median age 59 years, range 26-83). The overall median survival was 10.7 months. A higher Karnofsky performance status (p = 0.0001), a controlled primary (median survival = 11.6 vs. 8.8 months, p = 0.0023), absence of extracranial metastases (median survival 13.4 vs. 9.1 months, p = 0.0001), and lower RPA class (median survival 16.1 months for class I vs. 10.3 months for class II vs. 8.7 months for class III, p = 0.000007) predicted for improved survival. Gender, age, primary site, radiosurgery technique, and institution were not prognostic. The addition of RS boosted results in median survival (16.1, 10.3, and 8.7 months for classes I, II, and III, respectively) compared with the median survival (7.1, 4.2, and 2.3 months, p <0.05) observed in the RTOG RPA analysis for patients treated with WBRT alone. CONCLUSION: In the absence of randomized data, these results suggest that RS may improve survival in patients with BM. The improvement in survival does not appear to be restricted by class for well-selected patients.

High-dose intra-arterial cisplatin boost with hyperfractionated radiation therapy for advanced squamous cell carcinoma of the head and neck.

PURPOSE: To evaluate the tolerance and efficacy of intra-arterial (IA) cisplatin boost with hyperfractionated radiation therapy (HFX-RT) in patients with advanced squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Forty-two patients with locally advanced primary SCCHN were treated on consecutive phase I/II studies of HFX-RT (receiving a total of 76.8 to 81.6 Gy, given at 1.2 Gy bid) and IA cisplatin (150 mg/m(2) received at the start of and during RT boost treatment). RESULTS: Acute grade 3 to 4 toxicities were as follows: grade 4 and grade 3 mucosal toxicity occurred in three (7%) and 31 patients (69%), respectively, and grade 3 hematologic, infectious, and skin events occurred in one patient each. Eight of 24 patients (33%) were unable to receive a second planned dose of IA cisplatin because of general anxiety (n = 5), nausea and/or emesis (n = 2), or asymptomatic occlusion of an external carotid artery (n = 1). Thirty-seven patients (88%) experienced complete response (CR) at primary site. Twenty-nine (85%) of 34 patients presenting with nodal disease experienced CR. The actuarial 2-year rates of locoregional control and disease-specific and overall survival are 73%, 63%, and 57%, respectively, with a median active follow-up of 30 months. CONCLUSION: In this highly unfavorable subset of patients, these results seem superior to previously reported chemoradiation regimens in more favorable patients. Use of a second dose of IA cisplatin boost was associated with increased toxicity without obvious therapeutic gain. This novel strategy allows for an incremental increase in the treatment intensity of the HFX-RT regimen recently established as superior to once-a-day RT.

The prognostic significance of midline shift at presentation on survival in patients with glioblastoma multiforme.

PURPOSE: While patients with glioblastoma multiforme (GBM) who present with midline shift have a presumably worse prognosis, there is little literature evaluating the prognostic significance of this presentation in multivariate analysis in the context of other known prognostic factors. METHODS AND MATERIALS: From March 1981 to September 1993, 219 patients underwent irradiation for intracranial glioma at our institution. One hundred fourteen patients with a diagnosis of a primary GBM were analyzed for the influence of the presence of midline shift at diagnosis on survival with respect to other known prognostic factors, including age, Karnofsky performance status (KPS), and extent of surgery. Eighty-five patients (74%) presented with midline shift. Surgical treatment consisted of subtotal/total resection in 86 patients (75%). Among patients presenting with midline shift, 68 (80%) underwent subtotal/total resection before irradiation. RESULTS: Multivariate analysis of the entire cohort of patients found none of the potential prognostic factors analyzed to significantly influence survival. The overall median survival was 6 months. However, when multivariate analysis was limited to patients with a KPS of > or = 70, only the presence of midline shift and age were found to significantly influence survival. Patients with a KPS > or = 70 and with midline shift present at diagnosis had a median survival of 8 months, as compared to 14 months for those not having midline shift at presentation (p = 0.04). Patients with a KPS > or = 70 and age > 50 years had a median survival of 5 months as compared to 11 months for those < or = 50 (p = 0.02). CONCLUSION: In this series, where 80% of patients who presented with a midline shift underwent decompressive resection of GBM before irradiation, the presence of midline shift at diagnosis remained an independent prognostic factor influencing survival among good performance status patients. While the role of decompressive surgery in this setting is likely of some benefit, the extent of this benefit remains to be defined.

Prognostic significance of postchemoradiation stage following preoperative chemotherapy and radiation for advanced/recurrent rectal cancers.

PURPOSE: To evaluate the prognostic significance of postchemoradiation pathologic stage and implications for further therapy following preoperative chemoradiation and surgery for advanced/recurrent rectal cancer. METHODS AND MATERIALS: Seventy-seven patients with advanced (fixed or tethered T4) or recurrent rectal cancer were treated with preoperative chemoradation followed by surgical resection of disease. Chemotherapy consisted of either of bolus 5-FU 500 mg/m(2) per day or continuous venous infusion 225 mg/m(2) per day for the duration of radiation. Radiation therapy was planned to be delivered to the whole pelvis to a dose of 45 Gy followed by a boost to the area of the tumor of 5-15 Gy. Total radiation doses ranged from 40 to 63 Gy with a median of 55.8 Gy. Surgical resection was then carried out 6-10 weeks following the completion of treatment (median, 7 weeks). Twenty-eight patients underwent abdominoperineal resection and and 49 patients had sphincter-sparing surgical procedures. None of the patients received postoperative chemotherapy. Follow-up in these patients ranges from 1 year to 8 years with a median of 3 years. RESULTS: Significant downstaging of disease was observed with 12/77 (16%) having no residual disease(pT0) and 13% (10/77) found to have pT1-2, N0 disease, 31% (24/77) with pT3-4, N0 and 40% (31/77) for pT0-4, N1-2 cancers. Survival by pathologic stage was 100% for pT0-2, N0 cancers, 80% for pT3-4, N0 and 73% for pTx, N1-2. Local recurrence of disease was observed in 0% of patients with pT0-2, N0 as compared with 13% (3/24) in pT3-4, N0 and 16% (5/31) in pT0-4, N1-2 patients. CONCLUSION: Downstaging following preoperative chemoradiation is a significant prognostic factor. Patients with pT0, T1, or T2 disease have an excellent prognosis and are unlikely to fail locally or with systemic disease. However, patient with T3/T4 or N+ disease may benefit from further adjuvant chemotherapy.

Preliminary report of a phase I study of combined fractionated stereotactic radiosurgery and conventional external beam radiation therapy for unfavorable gliomas.

PURPOSE: To determine the tolerance and toxicities of fractionated stereotactic radiosurgery (FSRS) given in combination with conventional external beam radiation therapy (CEBRT). METHODS AND MATERIALS: From March 1995 to September 1998, 14 patients with previously unirradiated and unfavorable glioma (malignant glioma, n = 8; unfavorable low-grade glioma, n = 5; and recurrent glioma, n = 1) were stratified into 3 groups according to tumor volume (TV) to determine the initial FSRS dose schedule: Group A (n = 3): TV /=50% reduction, n = 2) or minor (>20% reduction, n = 9) imaging response. Follow-up ranged from 9 to 51 months (median 15 months), with 7 patients alive at 22-51 months. CONCLUSIONS: Imaging response and the ability of these patients with unfavorable intracranial gliomas to complete therapy without interruption or experiencing disease progression is very encouraging. Excessive toxicity of combined FSRS and CEBRT as evaluated thus far in this study was seen for patients with group B/C lesions. Evaluation of this novel treatment strategy with dose modification is ongoing.

The feasibility of dose escalation using concurrent radiation and 5-fluorouracil therapy following pancreaticoduodenectomy for pancreatic carcinoma.

We evaluated the feasibility of dose escalation using external beam radiation therapy (RT) and 5-fluorouracil (5-FU) following pancreaticoduodenectomy for pancreatic carcinoma. Fourteen patients who underwent pancreaticoduodenectomy for stage I-III adenocarcinoma of the pancreas received postoperative high-dose chemoradiation. RT was given at 1.8-Gy daily fractions to total doses of 54 Gy for patients with negative surgical margins (n = 12), and 64.8 Gy for those with gross residual disease (n = 2). Concurrent 5-FU was given as a continuous infusion (CI) at 225 mg/m2 per day (n = 9) beginning or day 1 and continuing until the completion of RT, or by bolus injection at 500 mg/m2 per day (n = 5) during weeks 1 and 4 of RT. Follow-up ranged from 32 to 36 months (median, 35 months). All patients were able to complete the planned high-dose postoperative chemoradiation and none required a treatment break. No grade 4 acute toxicity was observed. Grade 3 acute toxicity was limited to 2 patients. Two patients developed grade 3 (n = 1) or 4 (n = 1) subacute toxicity, all gastrointestinal-related. There have been no fatal toxicities and no grade 3 or 4 late toxicity has been observed. The 3-year survival is 21%. Dose escalation of postoperative 5-FU chemoradiation following pancreaticoduodenectomy for pancreatic carcinoma is well tolerated. Further dose-intensification of postoperative adjuvant therapy in these patients appears feasible and is being evaluated in a recently activated national trial.

High-dose intra-arterial cisplatin and concurrent hyperfractionated radiation therapy in patients with locally advanced primary squamous cell carcinoma of the head and neck: report of a phase II study.

BACKGROUND: This phase II study evaluates the tolerability and efficacy of concurrent hyperfractionated radiation therapy (HFX-RT) and high-dose intra-arterial (IA) cisplatin in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). METHODS: Between December 1995 and November 1997, 20 patients with locally advanced T4/T3 SCCHN were treated with HFX-RT (76.8-79.2 Gy at 1.2 Gy bid over 6-7 weeks) and high-dose IA cisplatin (150 mg/m(2) given at the start of RT boost treatment [start of week 6]). Seventeen patients (85%) had T4 disease, and 14 (70%) had N2/ N3 disease. RESULTS: Grade 3-5 acute toxicity was limited to one grade 4 (5%) and 14 grade 3 (70%) mucosal events. No grade 3/4 hematologic toxicity was observed. Median weight loss during therapy was 9% (range, 2%-16%). Eighteen patients had complete response (90%) at the primary site; 14 were confirmed pathologically. Among 17 patients with positive neck disease, 16 (94%) achieved complete response in the neck, including 12 of 13 patients with N2/N3 disease who underwent planned neck dissection. Active follow-up ranges from 12 to 32 months (median, 20 months) with 11 patients alive without disease, 5 dead of disease, and 4 dead of intercurrent disease. Eighteen patients (90%) remained disease free at the primary site, and the locoregional control rate is 80%. CONCLUSIONS: High-dose IA cisplatin and concurrent HFX-RT as used in this study is feasible and warrants further investigation. The high complete response rate and low grade 4 toxicity in this highly unfavorable subset of patients appears better than previously reported chemoradiation regimens for more favorable patients.

Preoperative chemoradiation in fixed distal rectal cancer: dose time factors for pathological complete response.

PURPOSE: Preoperative chemoradiation is being utilized extensively in the treatment of rectal cancer. However, a variety of dose time factors in both delivery of chemotherapy and irradiation remain to be established. This study was undertaken to examine the impact of dose time factors on pathological complete response (pCR) rates following preoperative chemoradiation for fixed rectal cancer. METHODS AND MATERIALS: Thirty-three patients with fixed rectal cancers were treated with combined 5-fluorouracil (5-FU) chemotherapy and pelvic radiation. Twenty-one patients received bolus 5-FU during the first 3-5 days of radiation and repeated on days 28-33 of their radiation treatment. Twelve patients were treated with continuous infusion (CI) 5-FU, 225 mg/m(2) for the duration of the pelvic radiation. Fifteen patients received a planned total radiation dose of 45 to 50 Gy and 18 patients received a dose of 55 to 60 Gy. Surgical resection was then carried out 6-8 weeks after completion of treatment. RESULTS: Diarrhea was the most frequent acute toxicity. Grade 3 diarrhea was observed in 6 patients requiring treatment interruption and was not related to the chemotherapy regimen. There was no Grade 4 or 5 toxicity. pCR was observed in 2 of 21 (10%) patients treated with bolus 5-FU as compared to 8 of 12 (67%) for patients treated with CI (p = 0.002). pCR were observed in 8 of 18 (44%) patients receiving radiation dose > or = 5500 cGy as compared to 2 of 15 (13%) patients treated to a dose < or = 5000 cGy (p = 0.05). In the high-dose radiation (> or = 5500 cGy) group, a significant difference in pCR rate was observed in patients treated with CI, 8 of 12 (67%) (p = 0.017) as compared with bolus 5-FU (0 of 6). There was no significant difference in operative morbidity or in wound healing between patients treated with bolus 5-FU or CI or within the groups treated with low or high doses of radiation. Three patients have developed local recurrence at 14 and 24 months, two in the low-dose group treated with bolus 5-FU and one patient in the CVI group. The overall 5-year survival for the whole group is 71%. CONCLUSION: Dose intensity of 5-FU and dose of radiation correlate significantly with the likelihood of achieving a pCR. Continuous infusion 5-FU (CI) and a preoperative radiation dose of 5500 cGy or higher can achieve pCR rates of approximately 50%, even in fixed cancers of the rectum.

Gamma knife radiosurgery using 90 Gy for trigeminal neuralgia.

OBJECT: The purpose of this paper was to assess the treatment of trigeminal neuralgia (TN) with the higher than normal dose of 90 Gy. METHODS: Forty-two patients with typical TN were treated over a 3-year period with gamma knife radiosurgery. Every patient received a maximum dose of 90 Gy in a single 4-mm isocenter targeted to the root entry zone of the trigeminal nerve. Thirty of 42 patients had undergone no prior treatments. The median follow-up period was 14 months (range 2-30 months). Thirty-one patients (73.8%) achieved complete relief of pain. Nine patients (21.4%) obtained good pain control. Complications were limited to increased facial paresthesia in seven patients (16.7%) and dysgeusia in four patients (9.5%). CONCLUSIONS: The authors conclude that the use of 90 Gy is a safe and effective dose for the treatment of TN.

Combined stereotactic split-course fractionated gamma knife radiosurgery and conventional radiation therapy for unfavorable gliomas: a phase I study.

OBJECT: This investigation was performed to determine the tolerance and toxicities of split-course fractionated gamma knife radiosurgery (FSRS) given in combination with conventional external-beam radiation therapy (CEBRT). METHODS: Eighteen patients with previously unirradiated, gliomas treated between March 1995 and January 2000 form the substrate of this report. These included 11 patients with malignant gliomas, six with low-grade gliomas, and one with a recurrent glioma. They were stratified into three groups according to tumor volume (TV). Fifteen were treated using the initial FSRS dose schedule and form the subject of this report. Group A (four patients), had TV of 5 cm3 or less (7 Gy twice pre- and twice post-CEBRT); Group B (six patients), TV greater than 5 cm3 but less than or equal to 15 cm3 (7 Gy twice pre-CEBRT and once post-CEBRT); and Group C (five patients), TV greater than 15 cm3 but less than or equal to 30 cm3 (7 Gy once pre- and once post-CEBRT). All patients received CEBRT to 59.4 Gy in 1.8-Gy fractions. Dose escalation was planned, provided the level of toxicity was acceptable. All patients were able to complete CEBRT without interruption or experiencing disease progression. Unacceptable toxicity was observed in two Grade 4/Group B patients and two Grade 4/Group C patients. Eight patients required reoperation. In three (38%) there was necrosis without evidence of tumor. Neuroimaging studies were available for evaluation in 14 patients. Two had a partial (> or = 50%) reduction in volume and nine had a minor (> 20%) reduction in size. The median follow-up period was 15 months (range 9-60 months). Six patients remained alive for 3 to 60 months. CONCLUSIONS: The imaging responses and the ability of these patients with intracranial gliomas to complete therapy without interruption or experiencing disease progression is encouraging. Excessive toxicity derived from combined FSRS and CEBRT treatment, as evaluated thus far in this study, was seen in patients with Group B and C lesions at the 7-Gy dose level. Evaluation of this novel treatment strategy with dose modification is ongoing.

High-dose spatially-fractionated radiation (GRID): a new paradigm in the management of advanced cancers.

PURPOSE: With the advent of megavoltage radiation, the concept of spatially-fractionated (SFR) radiation has been abandoned for the last several decades; yet, historically, it has been proven to be safe and effective in delivering large cumulative doses (> 100 Gy) of radiation in the treatment of cancer. SFR radiation has been adapted to megavoltage beams using a specially constructed grid. This study evaluates the toxicity and effectiveness of this approach in treatment of advanced and bulky cancers. METHODS AND MATERIALS: From January 1995 through March 1998, 71 patients with advanced bulky tumors (tumor sizes > 8 cm) were treated with SFR high-dose external beam megavoltage radiation using a GRID technique. Sixteen patients received GRID treatments to multiple sites and a total of 87 sites were irradiated. A 50:50 GRID (open to closed area) was utilized, and a single dose of 1,000-2,000 cGy (median 1,500 cGy) to Dmax was delivered utilizing 6 MV photons. Sixty-three patients received high-dose GRID therapy for palliation (pain, mass, bleeding, or dyspnea). In 8 patients, GRID therapy was given as part of a definitive treatment combined with conventionally-fractionated external beam irradiation (dose range 5,000-7,000 cGy) followed by subsequent surgery. Forty-seven patients were treated with GRID radiation followed by additional fractionated external beam irradiation, and 14 patients were treated with GRID alone. Thirty-one treatments were delivered to the abdomen and pelvis, 30 to the head and neck region, 15 to the thorax, and 11 to the extremities. RESULTS: For palliative treatments, a 78% response rate was observed for pain, including a complete response (CR) of 19.5%, and a partial response (PR) of 58.5% in these large bulky tumors. A 72.5% response rate was observed for mass effect (CR 14.6%, PR 52.9%). The response rate observed for bleeding was 100% (50% CR, 50% PR) and for dyspnea, a 60% PR rate only. A relatively higher response rate (CR 23.3%, PR 60%) was observed in patients who received GRID treatment in the head and neck area. No grade 3 late skin, subcutaneous, mucosal, GI, or CNS complications were observed in any patient in spite of these high doses. In the 8 patients who received GRID treatment for definitive treatment, a clinical CR was observed in 5 patients (62.5%) and a pathological complete response was confirmed in the operative specimen in 4 patients (50%). CONCLUSION: The efficacy and safety of using a large fraction of SFR radiation was confirmed by this study and substantiates our earlier results. In selected patients with bulky tumors (> 8 cm), SFR radiation can be combined with fractionated external beam irradiation to yield improved local control of disease, both for palliation and selective definitive treatment, especially where conventional treatment alone has a limited chance of success.

Postoperative radiation therapy for primary vs. recurrent squamous cell carcinoma of the head and neck: results of a comparative analysis.

BACKGROUND: There is little literature comparatively evaluating the results of postoperative radiation therapy (RT) for patients with squamous cell carcinoma (SCC) of the head and neck treated for primary versus recurrent disease. METHODS: Between 1981 and 1993, 174 patients with SCC of the head and neck, 143 with primary and 31 with recurrent disease, were treated with standard postoperative RT. RESULTS: Patients treated for primary disease had 5-year local-regional control (LRC) and disease-specific survival (DSS) rates of 69% and 54%, respectively, as compared with 46% and 32%, respectively, for patients treated for recurrent disease (P = 0.03 and 0.04, respectively). On multivariate analysis, only tumor type (primary vs recurrent) significantly influenced LRC (P = 0.003) and only primary tumor site (oral cavity vs nonoral cavity) significantly influenced DSS (P = 0.04). Among the patients treated for recurrent disease, site of recurrence (undissected vs dissected tissue) significantly influenced both LRC and DSS (P = 0.008 and 0. 001, respectively). CONCLUSIONS: Patients with recurrent SCC of the head and neck do poorly as compared with those with primary disease when treated with standard postoperative RT, particularly when the recurrence is within previously dissected tissue. This patient group should be targeted for alternative treatment strategies.

Significance of pretreatment hemoglobin level in patients with T1 glottic cancer.

Recent reports have suggested that pretreatment hemoglobin level (Hgb) is significantly associated with local control (LC) and overall survival (OS) in patients with T1 and T2 squamous cell carcinoma of the glottic larynx. To further evaluate the association of pretreatment Hgb level and other factors with outcome, we performed a retrospective review limited to patients with T1 squamous cell carcinoma of the glottic larynx treated with external beam radiation therapy. One-hundred thirty-nine patients with T1 squamous cell carcinoma of the glottic larynx were analyzed. Median follow-up was 5 years (range 2-22). Median pretreatment Hgb was 14.4 gm/dl (range 8.2-17.2). The following parameters were analyzed for their impact on LC, OS, and disease specific survival (DSS): age; gender; pretreatment Hgb; tumor grade; anterior commissure involvement; field size; total dose; dose per fraction; and overall treatment time. Five-year actuarial LC was 84%. Pretreatment Hgb was not a significant predictor for LC when assessed as a continuous variable (P = 0.38), nor as a dichotomous variable with a cutoff at 13 gm/dl. Local control was 82% for patients with Hgb >13 vs. 92% for Hgb < or = 13 (P= 0.13). No other factor was significant for LC. Five-year actuarial OS was 74%. Univariate analysis revealed that, pretreatment Hgb, total dose, and patient age were significant factors for OS. Overall survival was 78% for patients with pretreatment Hgb > 13 gm/dl vs. 68% for patients with Hgb < or = 13 gm/dl (P = 0.004). Overall survival was 77% for patients treated with > 66 Gy vs. 67% for those treated with < or =66 Gy (P = 0.0013), and 80% for patients < or =61 years as opposed to 69% for patients older than 61 years (P = 0.017). Multivariate analysis revealed that only age (P = 0.014) and Hgb concentration (P = 0.001) retained significance. Five-year actuarial DSS was 92%. Pretreatment Hgb was not a prognostic factor for DSS, nor were any other analyzed factors. Pretreatment Hgb is not a significant prognostic factor for LC in patients with T1 squamous cell carcinoma of the glottic larynx, but it does predict for a poorer OS without affecting DSS. This suggests that patients with lower pretreatment Hgb may have confounding medical problems that detract from their overall survival.

Second malignant neoplasia in patients with T1 glottic cancer treated with radiation.

OBJECTIVE/HYPOTHESIS: To evaluate incidence, site of occurrence and outcome of second malignant neoplasia (SMN) in patients with T1 glottic cancer treated with radiation. STUDY DESIGN: Retrospective. METHODS: Between February 1964 and May 1993, 158 patients with T1 squamous carcinoma of the larynx were treated with definitive radiation. Incidence, site (aerodigestive tract or not) and outcome of SMN were analyzed. Median follow-up was 63 months (range, 12-245 mo). RESULTS: Thirty-four patients developed SMN, for an overall incidence of 22%. Twenty-four (67%) SMNs occurred in an aero-upper-digestive-tract site compared with nine (25%) occurring in a non-aero-upper-digestive tract site. The incidence of SMN observed was higher than would be expected for the general population at risk. The observed-to-expected ratios (OER) for all SMN, aero-upper-digestive SMN and non-aero-upper-digestive SMNs were 1.73, 5.53, and 0.62, respectively. Overall 5- and 10-year survivals were 76% and 57%, respectively, for those who did not develop SMN, as compared with 68% and 26%, for those who developed SMN (P = .003). Overall, 13 patients (8.2%) have died from laryngeal cancer, while 23 (15%) died from SMN (P = .001). CONCLUSION: This study confirms a higher incidence of SMN in T1 glottic cancer patients, compared with the general population. The majority of cases occur in aero-upper-digestive sites. These patients are more likely to die from their SMN than from glottic cancer. Patients with T1 squamous cell carcinoma of the glottic larynx represent a group of head and neck cancer patients who should be targeted in studies evaluating the potential benefits of chemoprevention, and aggressively counseled for social and/or behavioral modifications.

Adjuvant therapy for pancreatic cancer: current status.

Only 5% to 15% of patients with pancreatic adenocarcinoma are candidates for a potentially curative resection. Evidence that postoperative adjuvant therapy improves outcome has been limited to a single randomized trial of a well tolerated split-course, 5-Fluorouracil (5-FU) based, chemoradiation regimen. More aggressive regimens have since been developed and are associated with, at best, a modest improvement in patient outcome. The potentially significant morbidity associated with pancreaticoduodenectomy, which can compromise the delivery of postoperative adjuvant chemoradiation, has led to the development of preoperative (adjuvant/neoadjuvant chemoradiation) regimens in these patients. Although experience suggests that such an approach is feasible, the ultimate impact warrants further evaluation. In addition, despite evolving experiences towards more dose intensive pre or postoperative adjuvant chemoradiation regimens, the problem of distant metastases remains significant. New chemotherapeutic agents, such as gemcitabine, appear to have the potential to produce better results than those achieved over the last quarter century with 5-FU. A cooperative group study has recently been activated and is evaluating its impact in an adjuvant setting when given in addition to 5-FU based chemoradiation. In the meantime, ongoing investigations into optimal integration of different therapeutic modalities, along with advances in surgery, radiation, and systemic therapy, should lead us towards further improvements in outcomes for these patients.

Postoperative radiotherapy in the treatment of single metastases to the brain: a randomized trial.

CONTEXT: For the treatment of a single metastasis to the brain, surgical resection combined with postoperative radiotherapy is more effective than treatment with radiotherapy alone. However, the efficacy of postoperative radiotherapy after complete surgical resection has not been established. OBJECTIVE: To determine if postoperative radiotherapy resulted in improved neurologic control of disease and increased survival. DESIGN: Multicenter, randomized, parallel group trial. SETTING: University-affiliated cancer treatment facilities. PATIENTS: Ninety-five patients who had single metastases to the brain that were treated with complete surgical resections (as verified by postoperative magnetic resonance imaging) between September 1989 and November 1997 were entered into the study. INTERVENTIONS: Patients were randomly assigned to treatment with postoperative whole-brain radiotherapy (radiotherapy group, 49 patients) or no further treatment (observation group, 46 patients) for the brain metastasis, with median follow-up of 48 weeks and 43 weeks, respectively. MAIN OUTCOME MEASURES: The primary end point was recurrence of tumor in the brain; secondary end points were length of survival, cause of death, and preservation of ability to function independently. RESULTS: Recurrence of tumor anywhere in the brain was less frequent in the radiotherapy group than in the observation group (9 [18%] of 49 vs 32 [70%] of 46; P<.001). Postoperative radiotherapy prevented brain recurrence at the site of the original metastasis (5 [10%] of 49 vs 21 [46%] of 46; P<.001) and at other sites in the brain (7 [14%] of 49 vs 17 [37%] of 46; P<.01). Patients in the radiotherapy group were less likely to die of neurologic causes than patients in the observation group (6 [14%] of 43 who died vs 17 [44%] of 39; P=.003). There was no significant difference between the 2 groups in overall length of survival or the length of time that patients remained functionally independent. CONCLUSIONS: Patients with cancer and single metastases to the brain who receive treatment with surgical resection and postoperative radiotherapy have fewer recurrences of cancer in the brain and are less likely to die of neurologic causes than similar patients treated with surgical resection alone.