Hypofractionated accelerated radiotherapy using concomitant intensity-modulated radiotherapy boost technique for localized high-risk prostate cancer: acute toxicity results

PURPOSE: To evaluate the acute toxicities of hypofractionated accelerated radiotherapy (RT) using a concomitant intensity-modulated RT boost in conjunction with elective pelvic nodal irradiation for high-risk prostate cancer. METHODS AND MATERIALS: This report focused on 66 patients entered into this prospective Phase I study. The eligible patients had clinically localized prostate cancer with at least one of the following high-risk features (Stage T3, Gleason score >/=8, or prostate-specific antigen level >20 ng/mL). Patients were treated with 45 Gy in 25 fractions to the pelvic lymph nodes using a conventional four-field technique. A concomitant intensity-modulated radiotherapy boost of 22.5 Gy in 25 fractions was delivered to the prostate. Thus, the prostate received 67.5 Gy in 25 fractions within 5 weeks. Next, the patients underwent 3 years of adjuvant androgen ablative therapy. Acute toxicities were assessed using the Common Terminology Criteria for Adverse Events, version 3.0, weekly during treatment and at 3 months after RT. RESULTS: The median patient age was 71 years. The median pretreatment prostate-specific antigen level and Gleason score was 18.7 ng/L and 8, respectively. Grade 1-2 genitourinary and gastrointestinal toxicities were common during RT but most had settled at 3 months after treatment. Only 5 patients had acute Grade 3 genitourinary toxicity, in the form of urinary incontinence (n = 1), urinary frequency/urgency (n = 3), and urinary retention (n = 1). None of the patients developed Grade 3 or greater gastrointestinal or Grade 4 or greater genitourinary toxicity. CONCLUSION: The results of the present study have indicated that hypofractionated accelerated RT with a concomitant intensity-modulated RT boost and pelvic nodal irradiation is feasible with acceptable acute toxicity.     

Phase I trial of preoperative hypofractionated intensity-modulated radiotherapy with incorporated boost and oral capecitabine in locally advanced rectal cancer

PURPOSE: To determine the safety and efficacy of preoperative hypofractionated radiotherapy using intensity-modulated radiotherapy (IMRT) and an incorporated boost with concurrent capecitabine in patients with locally advanced rectal cancer. METHODS AND MATERIALS: The eligibility criteria included adenocarcinoma of the rectum, T3-T4 and/or N1-N2 disease, performance status 0 or 1, and age > or =18 years. Photon IMRT and an incorporated boost were used to treat the whole pelvis to 45 Gy and the gross tumor volume plus 2 cm to 55 Gy in 25 treatments within 5 weeks. The study was designed to escalate the dose to the gross tumor volume in 5-Gy increments in 3-patient cohorts. Capecitabine was given orally 825 mg/m(2) twice daily for 7 days each week during RT. The primary endpoint was the maximal tolerated radiation dose, and the secondary endpoints were the pathologic response and quality of life. RESULTS: Eight patients completed RT at the initial dose level of 55 Gy. The study was discontinued because of toxicity-six Grade 3 toxicities occurred in 3 (38%) of 8 patients. All patients went on to definitive surgical resection, and no patient had a pathologically complete response. CONCLUSION: This regimen, using hypofractionated RT with an incorporated boost, had unacceptable toxicity despite using standard doses of capecitabine and IMRT. Additional research is needed to determine whether IMRT is able to reduce the side effects during and after pelvic RT with conventional dose fractionation.     

Phase I study of hypofractionated dose-escalated thoracic radiotherapy for limited-stage small-cell lung cancer

PURPOSE: To determine the maximal tolerated dose of hypofractionated thoracic radiotherapy with concurrent chemotherapy for limited-stage small-cell lung cancer patients. METHODS AND MATERIALS: Three radiotherapy regimens were used. Radiotherapy was given in two phases: patients initially received 20 Gy in 10 fractions to gross tumor plus uninvolved mediastinal nodes, followed by a boost to gross disease of 30, 38, or 42 Gy in 15 fractions. Radiotherapy was planned with conformal techniques. All patients received four cycles of cisplatin (25 mg/m2) and etoposide (100 mg/m2) chemotherapy. Radiotherapy commenced with Day 1 of Cycle 2 of chemotherapy. All complete/near-complete responders were offered prophylactic cranial irradiation. The maximal tolerated dose of radiotherapy was based on the dose that caused unacceptably high rates of radiotherapy-related toxicity. RESULTS: Thirteen patients were accrued. All patients who commenced radiotherapy received all prescribed chemo- and radiotherapy. There were no treatment-related deaths. There was one Grade 3 acute nonhematologic toxicity in the 50-Gy group. Of the 6 patients given 58 Gy, 3 experienced acute Grade 3 esophagitis. With a median follow-up of 7 months, median overall survival was 9.5 months. CONCLUSIONS: The maximal tolerated dose of thoracic radiotherapy with concurrent chemotherapy on this trial was 50 Gy in 25 daily fractions.     

Accelerated superfractionated radiotherapy with concomitant boost for invasive bladder cancer

PURPOSE: To determine the toxicity and clinical effectiveness of accelerated superfractionated radiotherapy with delayed concomitant boost (ASCBRT) in locally invasive carcinoma of the bladder. METHODS AND MATERIALS: Between July 1997 and December 2001, 87 patients (unsuitable or refusing cystectomy) with invasive bladder cancer underwent ASCBRT. The mean patient age was 66 years (range 40-90). The stage distribution was as follows: 2 T1, 51 T2, 13 T3, and 21 T4. Initially, the whole pelvis was treated by 1.8-Gy conventional daily fractions up to a total dose of 45 Gy. A small field boost covering gross disease was added as a second daily fraction (1.5 Gy) during the last 3 weeks of the 5-week schedule up to a total dose of 67.5 Gy. The interfraction interval was a minimum of 6 h. The patients were evaluated in follow-up for toxicity, local control, and survival. RESULTS: All but 2 patients completed the study protocol. Grade 3 acute urinary toxicity was observed in 2 patients. Grade 2 and 3 late bladder toxicity was observed in 12 patients and 1 patient, respectively. Grade 2 and 3 late bowel toxicity was observed in 5 and 3 patients, respectively. The 3-year actuarial local control, distant disease control, cause-specific survival, and overall survival rate was 64%, 78%, 58%, and 46%, respectively. Multivariate analysis revealed T stage as independent predictor of complete response. For Stage T2 and T3, the 3-year local control rate was 77% and 48%, respectively. At the last follow-up, 53 patients (61%) were still alive with a survival time between 6 and 62 months. CONCLUSION: ASCBRT is feasible with acceptable tolerance even in relatively old patients with Stage T3 or greater tumor. The encouraging locoregional control and survival results of this institutional experience, favorable compared with conventional radical and other accelerated fractionated (with or without a concomitant boost) RT series, make ASCBRT worthy of further study in a Phase III trial.     

Efficacy of fractionated stereotactic reirradiation in recurrent gliomas: long-term results in 172 patients treated in a single institution.

PURPOSE: To evaluate the efficacy of fractionated stereotactic radiotherapy (FSRT) performed as reirradiation in 172 patients with recurrent low- and high-grade gliomas. PATIENTS AND METHODS: Between 1990 and 2004, 172 patients with recurrent gliomas were treated with FSRT as reirradiation in a single institution. Seventy-one patients suffered from WHO grade 2 gliomas. WHO grade 3 gliomas were diagnosed in 42 patients, and 59 patients were diagnosed with glioblastoma multiforme (GBM). The median time between primary radiotherapy and reirradiation was 10 months for GBM, 32 months for WHO grade 3 tumors, and 48 months for grade 2 astrocytomas. FSRT was performed with a median dose of 36 Gy in a median fractionation of 5 x 2 Gy/wk. RESULTS: Median overall survival after primary diagnosis was 21 months for patients with GBM, 50 months for patients with WHO grade 3 gliomas, and 111 months for patients with WHO grade 2 gliomas. Histologic grading was the strongest predictor for overall survival, together with the extent of neurosurgical resection and age at primary diagnosis. Median survival after reirradiation was 8 months for patients with GBM, 16 months for patients with grade 3 tumors, and 22 months for patients with low-grade gliomas. Only time to progression and histology were significant in influencing survival after reirradiation. Progression-free survival after FSRT was 5 months for GBM, 8 months for WHO grade 3 tumors, and 12 months for low-grade gliomas. CONCLUSION: FSRT is well tolerated and may be effective in patients with recurrent gliomas. Prospective studies are warranted for further evaluation.     

Simultaneous Modulated Accelerated Radiation Therapy and Concurrent Weekly Paclitaxel in the Treatment of Locally Advanced Nasopharyngeal Carcinoma

Objectives: To evaluate the feasibility and efficacy of simultaneous accelerated radiation therapy (SMART) andconcurrent weekly paclitaxel in the treatment of locally advanced nasopharyngeal carcinoma. Methods: Fortyonepatients with pathologically confirmed nasopharyngeal carcinoma were treated by SMART with concurrentweekly paclitaxel. Daily fraction doses of 2.5 Gy and 2.0 Gy were prescribed to the gross tumor volume (GTV)and clinical target volume (CTV) to a total dose of 70 Gy and 56 Gy, respectively. Paclitaxel of 45 mg/m2 wasadministered concurrently with radiation therapy every week. Adjuvant chemotherapy was given four weeksafter the completion of the radiotherapy (RT) if the tumor demonstrated only a partial response (PR). Results:All patients completed the radiotherapy (RT) course. Adjuvant chemotherapy was administered to 12 patientsdue to PR. The CR (complete remission) rate was 82.9% three months after RT. Thirty-nine (95.1%) patientscompleted the concurrent weekly chemotherapy with paclitaxel, and two patients skipped their sixth course.Seven patients had a 15% dosage reduction at the fifth and sixth course due to grade 3 mucositis. The medianfollow-up was 30 (range, 14-42) months. The three-year overall survival (OS), metastases-free survival (MFS),and local control rates were 77.0%, 64.4%, and 97.6%, respectively. No correlation between survival rate and Tor N stage was observed. Grade 3 acute mucositis and xerostomia were present in 17.1% and 7.1%, respectively.Conclusion: SMART with concurrent weekly paclitaxel is a potentially effective and toxicity tolerable approachin the treatment of locally advanced NPC.     

鼻咽癌后程X刀分次推量放疗的疗效观察

 目的 探讨鼻咽癌的放射治疗疗效。方法 将1996年至2000年常规放疗及后程X刀分次推量放疗的患者，按入组条件分为二组，分组进行肿瘤区有效生物剂量估计，低剂量区剂量估计，正常组织（口腔黏膜、唾液腺）剂量估计，近期疗效评价及1，3，5年生存率。结果 两组肿瘤区放射治疗有效生物剂量估计分别为83.23 Gy，99.09 Gy；两组咽旁间隙、茎突、颈动、静脉区低剂量区放射剂量估计分别为54.96 Gy，76.8 Gy；正常组织（口腔黏膜、唾液腺）剂量估计为66.24 Gy，53.76 Gy；两组完全缓解（CR）率、部分缓解（PR）率分别88.4 %，100 %及96.4 %，100 %；两组1，3，5年生存率分别为92.8 %，71.4 %，53.5 %；96.2 %，84.6 %，76.6 %。结论 后程X刀分次推量放疗提高了鼻咽癌常规放疗肿瘤区及低剂量区的放疗剂量，降低了正常组织的损伤剂量，是提高近期疗效及1，3，5年生存率的主要因素。临床放疗应严格筛选适应证，选择侵犯咽旁间隙、茎突、颈动、静脉区的病例为主。     

Hypofractionated intensity-modulated radiotherapy for primary glioblastoma multiforme

PURPOSE: A pilot study was designed to evaluate the safety and efficacy of a novel regimen of hypofractionated intensity-modulated radiotherapy (RT) in the adjuvant treatment of primary glioblastoma multiforme (GBM). The rationale of the study was to combine the potential radiobiologic advantage of hypofractionation to GBM with a highly conformal radiotherapeutic technique. The study was designed to measure the acute and chronic morbidity of patients treated with this regimen, response of GBM to the treatment, overall survival, and time to disease progression after therapy completion. METHODS AND MATERIALS: Twenty eligible patients were accrued between February 1999 and May 2000 for the study. All patients had Karnofsky performance scores of >/=70. All patients were treated with intensity-modulated RT using the NOMOS Peacock system. A dose of 50 Gy was delivered in 5-Gy daily fractions within 2 weeks to enhancing primary disease, residual tumor, or surgical cavity. Simultaneously, 30 Gy was prescribed in 3-Gy daily fractions to surrounding edema. The time to progression was measured with serial neurologic examinations and MRI or CT scans after RT completion. Acute and late toxicity was graded using Radiation Therapy Oncology Group neurotoxicity scores. RESULTS: Of the 20 patients, 18 were evaluated for outcome. The median time to disease progression was 6 months after RT completion. The median overall survival was 7 months after treatment completion. All recurrences were within 2 cm of the operative bed. Neurotoxicity during therapy was minimal, with all patients experiencing Grade 0 or 1 toxicity. Late toxicity included 10 patients with Grade 0, 2 patients with Grade 2, and 3 patients with Grade 4 toxicity, manifesting as brain necrosis requiring surgical reexcision. The survival of the 3 patients with brain necrosis was 23, 20, and 9 months. Mortality in all cases was the result of tumor recurrence, with no mortality resulting from brain necrosis. CONCLUSION: This regimen of hypofractionated intensity-modulated RT did not improve the time to disease progression or overall survival compared with historical experience using conventional fractionation. However, the treatment duration was reduced from 6 weeks to 2 weeks, which may be of palliative benefit in certain subsets of patients. This treatment regimen demonstrated a greater incidence of brain necrosis requiring surgical intervention; however, the 3 patients experiencing this toxicity had longer survival times. Future investigation may be useful to determine which fraction size may be optimal for GBM when highly conformal RT is used in the adjuvant setting.     

Fractionated stereotactic radiotherapy using gamma unit after hyperbaric oxygenation on recurrent high-grade gliomas

Background To reduce this complication and to enhance the radiation effect to hypoxic cells of high-grade gliomas, the authors performed noninvasive fractionated stereotactic radiotherapy (FSRT) using a Gamma unit combined with hyperbaric oxygen (HBO) therapy for the treatment of recurrent disease. Patients and methods Twenty-five consecutive patients who had previously received radiotherapy with chemotherapy for recurrent high-grade gliomas, including 14 patients with anaplastic astrocytoma (AA) and 11 with glioblastoma multiforme (GBM), underwent Gamma FSRT immediately after HBO therapy (2.5 atmospheres absolute for 60 min). The Gamma FSRT was repeatedly performed using a relocatable head cast. Median tumor volume was 8.7 cc (range, 1.7–159.3 cc), and the median total radiation dose was 22 Gy (range, 18–27 Gy) to the tumor margin in 8 fractions. Results Actuarial median survival time after FSRT was 19 months for patients with AA and 11 months for patients with GBM, which was significantly different (P = 0.012, log-rank test). Two patients underwent subsequent second FSRT for regional or remote recurrence. Seven patients (28%) underwent subsequent craniotomies and resections at a mean of 8.4 months after FSRT treatment, and 4 of them had radiation effects without viable cells and remained alive for 50–78 months. Conclusion Gamma FSRT after HBO therapy appears to confer a survival benefit for patients with recurrent high-grade gliomas and warrants further investigation.     

Fractionated stereotactic reirradiation and concurrent temozolomide in patients with recurrent glioblastoma

The aim of this paper is to evaluate the efficacy of fractionated stereotactic radiotherapy (FSRT) and concomitant temozolomide (TMZ) as a salvage treatment option in patients with recurrent glioblastoma (GBM). Between May 2006 and December 2009, 36 patients with recurrent GBM received FSRT plus concomitant TMZ at University of Rome La Sapienza, Sant’ Andrea Hospital. All patients had Karnofsky performance score ≥60 and were previously treated with standard conformal radiotherapy (RT) (60 Gy) with concomitant and adjuvant TMZ for 6–12 cycles. The median time interval between primary RT and reirradiation was 14 months. At the time of recurrence, all patients received FSRT plus concomitant daily TMZ at the dose of 75 mg/m², given 7 days per week from the first day of RT. Radiation dose was 37.5 Gy delivered in 15 fractions over 3 weeks. Median overall survival after FSRT was 9.7 months, and the 6- and 12-month survival rates were 84 and 33%, respectively. The median progression-free survival (PFS) was 5 months, and 6- and 12-month PFS rates were 42 and 8%, respectively. In univariate analysis, KPS (P = 0.04), the interval between primary RT and reirradiation (P = 0.02), and O6-methylguanine-DNA-methyltransferase (MGMT) methylation status at the time of diagnosis (P = 0.009) had an effect on survival; however, in multivariate analysis, only MGMT methylation was statistically significant (P = 0.03). In general, FSRT was well tolerated and the treatment was completed in all patients. Neurological deterioration due to radiation-induced necrosis occurred in three patients (8%). FSRT plus concomitant TMZ is a feasible treatment option associated with survival benefits and low risk of complications in selected patients with recurrent GBM. The potential advantages of combined chemoradiation schedules in patients with recurrent GBM need to be explored in future studies.     

Preliminary results of a phase I/II study of simultaneous modulated accelerated radiotherapy for nondisseminated nasopharyngeal carcinoma

PURPOSE: To present preliminary results of intensity-modulated radiotherapy (IMRT) with the simultaneous modulated accelerated radiotherapy (SMART) boost technique in patients with nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: Twenty patients who underwent IMRT for nondisseminated NPC at the Asan Medical Center between September 2001 and December 2003 were prospectively evaluated. Intensity-modulated radiotherapy was delivered with the "step and shoot" SMART technique at prescribed doses of 72 Gy (2.4 Gy/day) to the gross tumor volume, 60 Gy (2 Gy/day) to the clinical target volume and metastatic nodal station, and 46 Gy (2 Gy/day) to the clinically negative neck region. Eighteen patients also received cisplatin once per week. RESULTS: The median follow-up period was 27 months. Nineteen patients completed the treatment without interruption; the remaining patient interrupted treatment for 2 weeks owing to severe pharyngitis and malnutrition. Five patients (25%) had Radiation Therapy Oncology Group Grade 3 mucositis, whereas 9 (45%) had Grade 3 pharyngitis. Seven patients (35%) lost more than 10% of their pretreatment weight, whereas 11 (55%) required intravenous fluids and/or tube feeding. There was no Grade 3 or 4 xerostomia. All patients showed complete response. Two patients had distant metastases and locoregional recurrence, respectively. CONCLUSION: Intensity-modulated radiotherapy with the SMART boost technique allows parotid sparing, as shown clinically and by dosimetry, and might also be more effective biologically. A larger population of patients and a longer follow-up period are needed to evaluate ultimate tumor control and late toxicity.     

Salvage reirradiation for recurrent glioblastoma with radiosurgery: radiographic response and improved survival

Purpose To determine the radiographic and clinical efficacy of stereotactic single dose radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT) as salvage therapy for glioblastoma (GBM) at recurrence. Methods Thirty-six patients with pathologically proven recurrent GBM were treated with salvage reirradiation by either SRS or FSRT between March of 2001 and August of 2006. Thirty-one patients had an initial diagnosis of GBM. Five patients had a malignant transformation. All patients had received radiotherapy with a dose of 50–60 Gy, a median 13.6 months prior to reirradiation (range: 0.8–119 months). At the time of recurrence, 26 patients were treated with SRS with a median dose of 18 Gy (range: 12–20 Gy). FSRT was performed in ten patients with a dose of 36 Gy in six fractions, twice weekly. Follow-up included MRI and clinical examination every 2 months. Results Median survival time after SRS was 8.5 months, compared to 7.4 months after FSRT (P = 0.81). Of 26 patients treated with SRS, radiographic tumor response or stable disease was observed in eight (35%) patients and tumor progression was seen in 18 (65%) patients. Of 10 patients treated by FSRT, radiographic tumor response or stable disease was observed in four (40%) patients and tumor progression was observed in four (40%) patients (two lost to follow-up). Patients who responded to treatment had statistically improved survival compared to non-responders, with median survival of 15.8 vs. 7.3 months (P < 0.05). Conclusion Salvage reirradiation with SRS or FSRT for recurrent GBM results in radiographic response in a proportion of patients. Survival was significantly improved among patients who either responded or had stable disease after salvage reirradiation, compared to non-responders. Further study is warranted to investigate the method and time of reirradiation for recurrent GBM.     

Long-term outcomes of 60 Gy conventional radiotherapy combined with androgen deprivation for localized or locally advanced prostate cancer

BACKGROUND: Until 1998 in Japan, very few institutions were treating prostate cancer solely with radiotherapy (RT) >70 Gy and most were using < or =65 Gy in combination with hormone therapy. The present study reports the long-term results of RT combined with hormone therapy for localized and locally advanced prostate cancer. METHODS: We investigated 57 patients who were treated by external beam RT plus hormone therapy (median age 79 years, median prostate-specific antigen concentration 15.0 ng/ml) between 1992 and 1998. Patients received 40 Gy of radiation to the pelvis and an additional 20 Gy as a prostatic boost. Hormone therapy was begun on the first day of irradiation and continued thereafter. RESULTS: The median follow-up was 93.3 months and the 5 and 10 year actual overall survival rates were 67.8 and 32.6%, respectively, with 5 and 10 year cause-specific survival rates of 97.9 and 95.0%, respectively. The expected survival rate was 66.2% at 5 years, and overall survival was above expected survival. Only one patient developed severe proctitis (Grade 3). The 5 year occurrence of Grade 1/2 genitourinary toxicity was 23.2%. CONCLUSIONS: Combined RT and hormone therapy has a good long-term outcome without severe adverse events. The overall survival rate compares well with the expected survival rate.     

High-dose, single-fraction image-guided intensity-modulated radiotherapy for metastatic spinal lesions

PURPOSE: To report tumor control and toxicity for patients treated with image-guided intensity-modulated radiotherapy (RT) for spinal metastases with high-dose single-fraction RT. METHODS AND MATERIALS: A total of 103 consecutive spinal metastases in 93 patients without high-grade epidural spinal cord compression were treated with image-guided intensity-modulated RT to doses of 18-24 Gy (median, 24 Gy) in a single fraction between 2003 and 2006. The spinal cord dose was limited to a 14-Gy maximal dose. The patients were prospectively examined every 3-4 months with clinical assessment and cross-sectional imaging. RESULTS: The overall actuarial local control rate was 90% (local failure developed in 7 patients) at a median follow-up of 15 months (range, 2-45 months). The median time to local failure was 9 months (range, 2-15 months) from the time of treatment. Of the 93 patients, 37 died. The median overall survival was 15 months. In all cases, death was from progression of systemic disease and not local failure. The histologic type was not a statistically significant predictor of survival or local control. The radiation dose was a significant predictor of local control (p = 0.03). All patients without local failure also reported durable symptom palliation. Acute toxicity was mild (Grade 1-2). No case of radiculopathy or myelopathy has developed. CONCLUSION: High-dose, single-fraction image-guided intensity-modulated RT is a noninvasive intervention that appears to be safe and very effective palliation for patients with spinal metastases, with minimal negative effects on quality of life and a high probability of tumor control.     

Fractionated stereotactic radiotherapy boost and weekly paclitaxel in malignant gliomas clinical and pharmacokinetics results

Management of Malignant Gliomas continues to be a challenge. We prospectively studied the role of adding weekly Paclitaxel to Fractionated Stereotactic Radiation Therapy (FSRT) in the treatment of Malignant Gliomas. Twenty-three Glioblastoma Multiforme and two Anaplastic Astrocytoma were studied. Patients received 46 Gy at 2 Gy/fraction followed by a boost utilizing FSRT at a fraction of 2.5 Gy for 8 fractions. Paclitaxel is delivered concomitantly at 150 mg/m(2) weekly for six cycles. Eighteen patients had pharmacokinetic assays of Paclitaxel levels. All patients were followed until death or for a maximum of 36 months. The overall survival of the whole group was 14 months. The median survival for RPA prognostic classes III, IV, V, and VI were 20, 14, 12, and 11 months. Higher survival (14 months) was noted in the subtherapeutic phenytoin level group compared to 10 months in the therapeutic group (P=0.271). No grade 4 CTCAE (version 3.0) toxicities were observed. Enhanced survival was demonstrated with gross tumor resection (20.8 months), KPS > or =80 (18.7 months) and age < or =60 years (27 months) as compared to subtotal resection or biopsy (12.1 months, P< 0.005), KPS < or =70 (10.8 months, P=0. 005) and older age > 60 (10.46 months, P=0.006), respectively. Our study suggests that: i) the use of weekly Paclitaxel and FSRT in Gliomas is well tolerated with a survival of 14 months; ii) the regimen resulted in improvement of survival of RPA classes IV, V, VI; and iii) the use of FSRT boost may be studied with other chemotherapeutic agents to see if superior results can be attained.     

28例不能手术的肝外胆道系统肿瘤放化疗疗效分析

目的 评价放疗晚期肝外胆道系统肿瘤的疗效。方法 对28例手术不可切除的肝外胆道系统肿瘤采用放化疗，其中胆囊癌13例，肝外胆管癌15例。15例采用常规放疗，中位照射剂量45Gy（30～60Gy），13例采用三维适形放疗（3DcRT）多野（3～5个野）照射或加量，中位照射剂量55Gy（50～70Gy）。12例单纯放疗，16例放化结合。化疗方案为氟尿嘧啶500mg，2次／周，或氟尿嘧啶500mg＋顺铂30mg，1次／周，疗程3～6个周期。结果 全部患者近期有效率14％。全组中位生存期9．4个月（2～28个月）。1、2年生存率分别为38％、15％；其中1年生存率胆囊癌为46％，肝外胆管癌为27％，3DCRT为42％，常规放疗为33％，单纯放疗为37％，放疗＋化疗为31％；〈50Gy的为29％，≥50Gy的为45％。只有照射剂量（≥50Gy）对1年生存率有影响（X^2=5．31，P=0．023）。急性消化道反应1～2级为57％，3级为18％，仅有25％的出现1～2级血液毒性反应。结论 对晚期肝外胆道系统肿瘤采用放化疗可取得一定疗效，且副作用可耐受。     

Can concomitant-boost accelerated radiotherapy be adopted as routine treatment for head-and-neck cancers? A 10-year single-institution experience

PURPOSE: Accelerated schedules are effective in overcoming repopulation during radiotherapy (RT) for head-and-neck cancers, but their feasibility is compromised by increased toxicity. The therapeutic ratio may be particularly favorable for 5-week regimens. This study reports the 10-year experience of a single institution in the routine use of concomitant boost RT as standard radical treatment in all but the most favorable stage patients. METHODS AND MATERIALS: Between February 1991 and June 2001, 296 patients (mean age, 59 years) were treated with concomitant boost RT either alone (67%) or combined with cisplatin-based chemotherapy (33%), with a median tumor dose of 69.9 Gy. Tumors were located in the oropharynx in 52%, hypopharynx in 20%, larynx in 15%, nasopharynx in 7%, and oral cavity in 6%. International Union Against Cancer Stage III-IV disease represented 77% of tumors. The median follow-up for surviving patients was 55 months (range, 10-138 months). RESULTS: The RT schedule was completed to the prescribed dose in all but 1 patient. Twenty patients (7%) had a treatment interruption (median, 5 days; range, 2-35 days). Grade 3-4 Radiation Therapy Oncology Group acute toxicity was observed in 77% of patients, and nutritional support was required in 110 patients (37%). For all patients, the 5-year actuarial locoregional control and disease-free survival rate was 72% and 61%, respectively. In a multivariate analysis, only T and N stage was significantly associated with locoregional control and disease-free survival. Grade 3-4 late toxicity occurred in 14%, mostly bone and cartilage necrosis. CONCLUSIONS: The present, moderately accelerated, concomitant boost regimen is logistically feasible, causing minimal inconvenience to the technical staff and yielding a high rate of patient compliance. Concomitant chemotherapy administration is feasible provided that patients are carefully selected and supportive care is introduced in a timely fashion. Considering the manageable toxicity and the satisfactory tumor control obtained, this regimen represents a good choice when considering implementation of an altered RT fractionation schedule as standard treatment for head-and-neck cancers.     

Fractionated stereotactic conformal radiotherapy in the management of large chemodectomas of the skull base

PURPOSE: To evaluate the role of fractionated stereotactic conformal radiotherapy (FSRT) as a noninvasive method in the management of large chemodectomas of the skull base. METHODS AND MATERIALS: Twenty-two patients with chemodectomas of the skull base were treated with FSRT at our institution. Ten patients received primary RT, and 12 patients were treated for recurrent or progressive disease after primary surgery (8 patients) or embolization (4 patients). The median total dose was 57.6 Gy, with a median of 1.8 Gy/fraction. The median target volume was 71.8 cm3 (range, 10.5-212.2 cm3). The most common symptoms at the initial diagnosis were pulsatile tinnitus (16 patients), hearing loss (14 patients), and balance disturbance (14 patients). Twelve patients had additional cranial nerve deficits. RESULTS: The median follow-up was 5.7 years (range, 19-177 months). The actuarial overall survival rate was 89.5% at 5 and 10 years. The actuarial local control rate was 90.4% at 5 and 10 years. Seven patients (32%) had a partial response and 13 (59%) had stable disease of the irradiated chemodectoma. Two symptomatic patients developed recurrence after 19 and 32 months. Neurologic dysfunction improved or completely resolved in 59% and stabilized in 32%; 9% of patients experienced impairment of preexisting neurologic dysfunction. No patient developed new neurologic deficits after FSRT. RT was interrupted in 1 patient because of a maxillary bone abscess. In all other patients, no acute or late adverse reactions greater than Common Toxicity Criteria Grade 2 were seen. CONCLUSION: Fractionated stereotactic conformal radiotherapy is an effective and well-tolerated noninvasive treatment for chemodectomas, with excellent tumor control rates and a low risk of morbidity. It is an option for patients at greater risk of microsurgical resection or with residual and recurrent tumors.     

FSRT联合替莫唑胺治疗大体积脑转移瘤的对照研究

目的 回顾比较应用分次立体定向放疗(FSRT)±替莫唑胺治疗大体积脑转移瘤患者疗效及安全性。方法 2009—2017年间共84例脑转移瘤患者(体积≥ 6 cm³)纳入分析,其中同步放化疗组(CRT组) 与单纯放疗组(RT组)各42例。放疗方案为52.0~52.5 Gy分13~15次,3.5~4.0 Gy/次。疗中复查脑MRI,如病灶体积明显缩小则行疗中缩野。疗后2~3个月评估疗效。主要研究终点为LRFS,次要研究终点为IPFS、PFS、OS、BMSS及不良反应。采用Kaplan-Meier法计算生存率并Logrank法检验和单因素预后分析。结果 CRT、RT组的中位GTV体积分别为16.9、15.7 cm³,疗中缩野率分别为75%、34%(P=0.000)。CRT、RT组LC率分别为100%、98%。中位随访时间为16.1个月(2.1~105.7个月),CRT组LRFS、IPFS、PFS、OS、BMSS均显著优于RT组(P=0.040、0.022、0.045、0.013、0.006)。1—2级消化道不良反应CRT组高于RT组(33%∶26%,P=0.006),两组均无4— 5级不良反应发生。结论 FSRT联合替莫唑胺进一步提高了大体积脑转移瘤患者的LC率及生存率且未增加严重不良反应。