Dose escalation for metastatic spinal cord compression in patients with relatively radioresistant tumors.

PURPOSE: Radiotherapy alone is the most common treatment for metastatic spinal cord compression (MSCC) from relatively radioresistant tumors such as renal cell carcinoma, colorectal cancer, and malignant melanoma. However, the results of the "standard" regimen 30 Gy/10 fractions need to be improved with respect to functional outcome. This study investigated whether a dose escalation beyond 30 Gy can improve treatment outcomes. METHODS AND MATERIALS: A total of 91 patients receiving 30 Gy/10 fractions were retrospectively compared to 115 patients receiving higher doses (37.5 Gy/15 fractions, 40 Gy/20 fractions) for motor function and local control of MSCC. Ten further potential prognostic factors were evaluated: age, gender, tumor type, performance status, number of involved vertebrae, visceral or other bone metastases, interval from tumor diagnosis to radiotherapy, pretreatment ambulatory status, and time developing motor deficits before radiotherapy. RESULTS: Motor function improved in 18% of patients after 30 Gy and in 22% after higher doses (p = 0.81). On multivariate analysis, functional outcome was associated with visceral metastases (p = 0.030), interval from tumor diagnosis to radiotherapy (p = 0.010), and time developing motor deficits (p < 0.001). The 1-year local control rates were 76% after 30 Gy and 80% after higher doses, respectively (p = 0.64). On multivariate analysis, local control was significantly associated with visceral metastases (p = 0.029) and number of involved vertebrae (p = 0.043). CONCLUSIONS: Given the limitations of a retrospective study, escalation of the radiation dose beyond 30 Gy/10 fractions did not significantly improve motor function and local control of MSCC in patients with relatively radioresistant tumors.

Technical innovations of carinal resection for nonsmall-cell lung cancer.

BACKGROUND: We present our perioperative management of operable nonsmall-cell lung cancer invading the tracheobronchial bifurcation and the results obtained. METHODS: Fifty consecutive patients undergoing carinal surgery with radical lymphadenectomy over a 5-year period were studied. RESULTS: Eighteen patients (36%) were N2 and had chemoradiation (48 +/- 6 Gy) preoperatively. Surgery included 34 carinal pneumonectomies (24 right, 10 left), 11 carinal lobectomies (n = 6) or bilobectomies (n = 5), and 5 carinal resections, with (n = 3) and without (n = 2) reconstructions. Patients were ventilated through low tidal volume controlled techniques except during airway resection and reconstruction, during which the apneic (hyper) oxygenation techniques were used. High inspiratory oxygen concentrations, multiple collapse and reexpansions, hypoperfusion of the ipsilateral lung, and fluid overload were avoided. All patients but 1 were extubated in the operating room, 7 +/- 5 minutes after skin closure. Operative mortality (less than 30 days) and morbidity were 4% (n = 2) and 37% (n = 18), respectively. All resections but 1 (98%) R1 were complete. The number of resected nodes per patient was 9 +/- 2, and 7 (22%) of the 32 patients who had negative preoperative positron emission tomography results had micrometastatic mediastinal nodes. With a median follow-up of 38 months, actuarial 5-year and disease-free survivals were 51% and 47%, respectively. Disease-free survival was significantly affected by endobronchial extension (tracheobronchial angle invasion versus less than 0.5 cm from carina, p = 0.03) and nodal status (N0 versus N1-2, p = 0.02) in the multivariate analysis. CONCLUSIONS: Preoperative chemoradiation, carinal lobectomy, or left pneumonectomy, and radical lymphadenectomy do not worsen the therapeutic index of carinal surgery. The high incidence of micrometastatic nodes in positron emission tomography-negative patients justifies routine mediastinoscopy and radical lymphadenectomy.

Prognostic factors for local control and survival after radiotherapy of metastatic spinal cord compression.

PURPOSE: To evaluate potential prognostic factors for local control and survival after radiotherapy of metastatic spinal cord compression (MSCC). PATIENTS AND METHODS: The following potential prognostic factors were investigated retrospectively in 1,852 patients irradiated for MSCC: age, sex, performance status, primary tumor, interval between tumor diagnosis and MSCC (< or = 15 v > 15 months), number of involved vertebrae (one to two v > or = three), other bone metastases, visceral metastases, pretreatment ambulatory status, time of developing motor deficits before radiotherapy (faster, 1 to 14 v slower, > 14 days), and radiation schedule (short-course v long-course radiotherapy). RESULTS: On univariate analysis, improved local control of MSCC was associated significantly with favorable histology (breast cancer, prostate cancer, lymphoma/myeloma), no visceral metastases, and long-course radiotherapy. On multivariate analysis, absence of visceral metastases and radiation schedule maintained significance. On univariate analysis, improved survival was associated significantly with female sex, favorable histology, no visceral or other bone metastases, good performance status, being ambulatory before radiotherapy, longer interval between tumor diagnosis and MSCC, and slower development of motor deficits before radiotherapy. Long-course radiotherapy showed a trend. On multivariate analysis, histology, visceral metastases, other bone metastases, ambulatory status before radiotherapy, interval between tumor diagnosis and MSCC, and time of developing motor deficits maintained significance. CONCLUSION: Poorer local control after radiotherapy for MSCC is associated with visceral metastases and short-course radiotherapy. Long-course radiotherapy seems preferable for patients with more favorable prognoses, given that these patients may live long enough to develop MSCC recurrences. Long-term survival after radiotherapy for MSCC may be predicted if several prognostic factors are considered.

Epoetin alfa improves survival after chemoradiation for stage III esophageal cancer: final results of a prospective observational study.

PURPOSE: This prospective, nonrandomized study evaluates the effectiveness of epoetin alfa to maintain the hemoglobin levels at 12 to 14 g/dL (optimal range for tumor oxygenation) during chemoradiation for Stage III esophageal cancer and its impact on overall survival (OS), metastatic-free survival (MFS), and locoregional control (LC). METHODS AND MATERIALS: Ninety-six patients were included. Forty-two patients received epoetin alfa (150 IU/kg, 3 times a week) during radiotherapy, which was started at hemoglobin less than 13 g/dL and stopped at 14 g/dL or higher. Hemoglobin levels were measured weekly during RT. RESULTS: Both groups were balanced for age, sex, performance status, tumor length/location, histology, grading, T-stage/N-stage, chemotherapy, treatment schedule, and hemoglobin before RT. Median change of hemoglobin was +0.3 g/dL/wk with epoetin alfa and -0.5 g/dL/wk without epoetin alfa. At least 60% of hemoglobin levels were 12 to 14 g/dL in 64% and 17% of the patients, respectively (p < 0.001). Patients who received epoetin alfa had better OS (32% vs. 8% at 2 years, p = 0.009) and LC (67% vs. 15% at 2 years, p = 0.001). MFS was not significantly different (42% vs. 18% at 2 years, p = 0.09). CONCLUSIONS: The findings suggest that epoetin alfa when used to maintain the hemoglobin levels at 12 to 14 g/dL can improve OS and LC of Stage III esophageal cancer patients.

Short-course radiotherapy is not optimal for spinal cord compression due to myeloma.

PURPOSE: To investigate the suitability of short-course radiotherapy (RT) for spinal cord compression (SCC) in myeloma patients. METHODS AND MATERIALS: Data for 172 myeloma patients irradiated between January 1994 and December 2004 for SCC were retrospectively evaluated. Short-course RT (1 x 8 Gy, 5 x 4 Gy, n = 61) and long-course RT (10 x 3 Gy, 15 x 2.5 Gy, 20 x 2 Gy, n = 111) were compared for functional outcome up to 24 months after RT. In addition, 10 potential prognostic factors were investigated. RESULTS: Improvement of motor function occurred in 90 patients (52%). Forty-seven percent of nonambulatory patients regained the ability to walk. Functional outcome was significantly influenced by the time of developing motor deficits before RT. Improvement of motor function was more frequent after long-course RT than after short-course RT: 59% vs. 39% (p = 0.10) at 1 month, 67% vs. 43% (p = 0.043) at 6 months, 76% vs. 40% (p = 0.003) at 12 months, 78% vs. 43% (p = 0.07) at 18 months, and 83% v 54% (p = 0.33) at 24 months. A subgroup analysis of the long-course RT group demonstrated a similar functional outcome for 10 x 3 Gy when compared with 15 x 2.5 Gy and 20 x 2 Gy. CONCLUSIONS: Long-course RT is preferable for SCC in myeloma patients because it resulted in better functional outcome than short-course RT. Treatment with 10 x 3 Gy can be considered appropriate.

Short-course radiotherapy (RT) for metastatic spinal cord compression (MSCC) due to renal cell carcinoma: results of a retrospective multi-center study.

OBJECTIVE: For MSCC treatment, a short treatment time is desirable, especially if survival prognosis is poor. Survival depends on the primary tumor, extent of disease, performance status, ambulatory status, and the number of involved vertebrae. These factors may help to define the appropriate regimen for the individual patient. Our study compares short-course (1 x 8 Gy, 5 x 4 Gy) and long-course RT (10 x 3 Gy, 15 x 2.5 Gy, 20 x 2 Gy) for functional outcome in MSCC patients with renal cell carcinoma. METHODS: The following potential prognostic factors for functional outcome were retrospectively investigated: age, performance status, involved vertebra, ambulatory status, time of developing motor deficits before RT, radiation schedule (short-course RT, n=37; long-course RT, n=50). RESULTS: Eighty-seven patients were included in this retrospective study, 25 patients (29%) showed improvement of motor function, 52 patients (60%) no change, 10 patients (11%) deterioration. 25% of non-ambulatory patients became ambulatory after RT. Functional outcome was affected by the time of developing motor deficits before RT (p<0.001). The RT schedule had no significant impact (p=0.91). In the short-course RT sub-group, functional outcome was similar for 1 x 8 Gy and 5 x 4 Gy (p=0.99). CONCLUSION: Short-course and long-course RT appear similarly active for MSCC in patients with renal cell carcinoma. Short-course RT appears preferable, as it is means less patient discomfort. Because 1 x 8 Gy and 5 x 4 Gy were comparably effective, 1 x 8 Gy may be suggested the best actual choice.

Reducing the overall treatment time for radiotherapy of metastatic spinal cord compression (MSCC): 3-year results of a prospective observational multi-center study.

BACKGROUND: This prospective multi-center study investigates a reduction of the overall treatment time for radiotherapy of MSCC, which is important for these mostly disabled patients. PATIENTS AND METHODS: Two standard fractionation schedules, 30 Gy/10 fractions/2 weeks (n = 71) and 40 Gy/20 fractions/4 weeks (n = 65) were compared for functional outcome and ambulatory status. Motor function was graded using an 8-point-scale before RT, at the end and at 6, 12 and 24 weeks after RT. A multi-variate analysis was performed for functional outcome. Included variables were the fractionation schedule and the three relevant prognostic factors. These factors are the type of primary tumor, the time of developing motor deficits before RT and the pre-treatment ambulatory status. RESULTS: The ambulatory rates were 49% in the 30 Gy group and 52% in the 40 Gy group before RT (P = 0.888), and 56% and 60% after RT (P = 0.888). Improvement of motor function occurred in 45% of the 30 Gy group and 40% of the 40 Gy group (P = 0.752). The relevant prognostic factors were comparably distributed in both groups. According to the multivariate analysis, a slower development of motor deficits (P < 0.001), a favorable histology (P = 0.040) and being ambulatory (P = 0.045) were associated with better functional outcome, whereas the fractionation schedule had no significant impact (P = 0.311). CONCLUSIONS: The data suggest both schedules to be comparably effective for functional outcome. Thus, 30 Gy/10 fractions/2 weeks should be applied instead of 40 Gy/20 fractions/4 weeks. The reduction of the overall treatment time from 4 to 2 weeks means less discomfort for the paraparetic or paraplegic patient.

A prospective evaluation of two radiotherapy schedules with 10 versus 20 fractions for the treatment of metastatic spinal cord compression: final results of a multicenter study.

BACKGROUND: The optimal treatment of patients with metastatic spinal cord compression (MSCC) is still being debated. The current observational multicenter study, performed prospectively by the authors, evaluated two radiotherapy (RT) schedules and prognostic factors with respect to functional outcome METHODS: In the current study, 214 patients with MSCC were irradiated between April 2000 and September 2003 with 30 gray (Gy) per 10 fractions per 2 weeks (n = 110) or with 40 Gy per 20 fractions per 4 weeks (n = 104). Motor function and ambulatory status were evaluated before RT and until 6 months after RT. The following potential prognostic factors were investigated: RT schedule, performance status, age, number of irradiated vertebrae, type of primary tumor, pretreatment ambulatory status, and length of time developing motor deficits before RT. RESULTS: Both groups were balanced for patient characteristics and potential prognostic factors. Motor function improved in 43% of patients after 30 Gy and in 41% of patients after 40 Gy (P = 0.799). Posttreatment ambulatory rates were 60% and 64% (P = 0.708), respectively. A multivariate analysis demonstrated that a slower progression of motor deficits before RT (P < 0.001), a favorable histology of the primary tumor (P < 0.001), and being ambulatory before RT (P = 0.035) were associated with a better functional outcome. RT schedule (P = 0.269) and other variables had no significant impact. Acute toxicity was mild, and late toxicity was not observed during the period of follow-up. Follow-up was 12 (6-28) months in patients surviving >/= 6 months. CONCLUSIONS: Thirty gray per 10 fractions was preferable to 40 Gy per 20 fractions, because it was associated with similar outcome, less treatment time, and lower costs. The type of tumor, pretreatment ambulatory status, and length of time developing motor deficits before RT were relevant prognostic factors and should be considered in future studies.