Patterns of failure following radiation with and without chemotherapy in patients with nasopharyngeal carcinoma

PURPOSE: Aim of this study was to retrospectively evaluate patterns of failure, results, and prognostic factors for patients with nasopharyngeal cancer (NPC) following radiotherapy (RT) with and without concurrent chemotherapy (RCT). PATIENTS AND METHODS: Between 1978 and 1999, a total of 101 patients with NPC were treated in our hospital, of whom 53 received external megavoltage RT alone with a median total dose of 76 Gy (1978-1988), and 48 patients had RCT (1989-1999). For RCT a combination of 5-FU and cisplatin was used together with a median total dose of 72 Gy. Patterns of relapse, survival rates and toxicity as well as prognostic factors were evaluated retrospectively. RESULTS: RCT was associated with a marked reduction in distant metastases: 6/48 (13%) vs. 17/53 (32%) after RT alone. Locoregional tumor persistence was only marginally lower with RCT: 10/48 (21%) vs. 17/53 (32%) following RT. Patients with RCT demonstrated a survival advantage compared to those with RT alone (5-year overall survival (OS): 64% vs. 44%, p = 0.1). OS, disease-specific survival and locoregional control rates were 53, 57, and 78% at 5 years and 47, 51 and 78% at 10 years, respectively. OS was significantly affected by histology (p = 0.007), the patients' age (p = 0.009) and gender (p = 0.01). CONCLUSION: This retrospective study provides further evidence that both reduction of distant metastasis and enhanced local tumor control by combined radiochemotherapy may be associated with improved survival rates in NPC compared to radiation alone. Concurrent RCT is therefore considered the preferable treatment option, however, confirmation in randomized trials is still warranted.     

Postoperative concomitant irradiation and chemotherapy with mitomycin C and bleomycin for advanced head-and-neck carcinoma

PURPOSE: In a prospective randomized clinical study, simultaneous postoperative application of irradiation (RT), mitomycin C, and bleomycin was tested in a group of patients with operable advanced head-and-neck carcinoma. It was expected that the planned combined postoperative therapy would reduce the number of locoregional recurrences and prolong survival. METHODS AND MATERIALS: A total of 114 eligible patients with Stage III or IV squamous cell head-and-neck carcinoma were randomized to receive postoperative RT alone (Group 1) or RT combined with simultaneous mitomycin C and bleomycin (Group 2). Patients were stratified according to the stage and site of the primary tumor and the presence or absence of high-risk prognostic factors. Primary surgical treatment was performed with curative intent in all patients. Patients in both groups were postoperatively irradiated to the total dose of 56-70 Gy. Chemotherapy included mitomycin C 15 mg/m(2) after 10 Gy and 5 mg of bleomycin twice a week during RT to the planned total dose of 70 mg. RESULTS: At 2 years, patients in the radiochemotherapy group had better locoregional control (86%) than those in the RT alone group (69%; p = 0.037). Disease-free survival and overall survival was also better in the radiochemotherapy group compared with the RT-alone group (76% vs. 60%, p = 0.099; and 74% vs. 64%, p = 0.036, respectively). Patients who benefited from chemotherapy were those with high-risk factors. CONCLUSION: The results of the present study indicate that concomitant postoperative radiochemotherapy with mitomycin C and bleomycin improves locoregional control and survival in patients with advanced head-and-neck carcinoma. The patients who benefited from chemotherapy were those with high-risk factors.     

Radiotherapy alone or combined with carbogen breathing for squamous cell carcinoma of the head and neck: a prospective, randomized trial

BACKGROUND: The current study was performed to investigate the efficacy of carbogen (95% oxygen [O(2)] and 5% carbon dioxide [CO(2)]) breathing during definitive radiotherapy (RT) to enhance local control. METHODS: Between November 1996 and November 2002, 101 patients with previously untreated T2 to T4 squamous cell carcinomas of the oropharynx, larynx, and hypopharynx were entered onto a prospective trial and randomized to receive definitive hyperfractionated RT alone or combined with carbogen breathing. Patients were stratified according to T classification and primary tumor site. Follow-up ranged from 1-91 months (median, 38 months). All living patients had follow-up for more than 2 years. Outcomes analyses were performed according to intent to treat. RESULTS: Definitive RT alone was completed as planned in 50 of 51 patients (98%); 49 of the 50 patients (98%) who were randomized to receive carbogen breathing were able to complete the RT as planned. Three patients randomized to receive carbogen breathing declined carbogen. The 5-year outcomes after RT alone or combined with carbogen were as follows: local control, 83% versus 88% (P = 0.5155); locoregional control, 81% versus 83% (P = 0.7174); distant metastasis-free survival, 82% versus 86% (P = 0.5184); cause-specific survival, 73% versus 77% (P = 0.5866); and absolute survival, 53% versus 58% (P = 0.4856). CONCLUSIONS: The addition of carbogen breathing to definitive RT did not appear to improve the likelihood of local control significantly. However, because of the limited size of the current study, the authors cannot definitively conclude that carbogen breathing is ineffective.     

Patterns of failure in patients with locally advanced head and neck cancer treated postoperatively with irradiation or concomitant irradiation with Mitomycin C and Bleomycin

PURPOSE: The long term results and patterns of failure in patients with squamous cell head and neck carcinoma (SCHNC) treated in a prospective randomized trial in which concomitant postoperative radiochemotherapy with Mitomycin C and Bleomycin (CRT) was compared with radiotherapy only (RT), were analyzed. PATIENTS AND METHODS: Between March 1997 and December 2001, 114 eligible patients with Stage III or IV SCHNC were randomized. Primary surgical treatment was performed with curative intent in all patients. Patients in both groups were postoperatively irradiated to the total dose of 56-70 Gy. Chemotherapy included Mitomycin C 15 mg/m2 after 10 Gy and 5 mg of Bleomycin twice weekly during irradiation. Median follow-up was 76 months (48-103 months). RESULTS: At 5 years in the RT and CRT arms, the locoregional control was 65% and 88% (p = 0.026), disease-free survival 33% and 53% (p = 0.035), and overall survival 37% and 55% (p = 0.091) respectively. Patients who benefited from chemotherapy were those with high-risk factors. The probability of distant metastases was 22% in RT and 20% in CRT arm (p = 0.913), of grade III or higher late toxicity 19% in RT and 26% in CRT arm (p = 0.52) and of thyroid dysfunction 36% in RT and 56% in CRT arm (p = 0.24). The probability to develop a second primary malignancy (SPM) was 34% in the RT and 8% in the CRT arm (p = 0.023). One third of deaths were due to infection, but there was no difference between the 2 groups. CONCLUSION: With concomitant radiochemotherapy, locoregional control and disease free survival were significantly improved. Second primary malignancies in the CRT arm compared to RT arm were significantly less frequent. The high probability of post treatment hypothyroidism in both arms warrants regular laboratory evaluation.     

Fifteen-year results of a randomized prospective trial of hyperfractionated chest wall irradiation versus once-daily chest wall irradiation after chemotherapy and mastectomy for patients with locally advanced noninflammatory breast cancer

PURPOSE: To analyze the results of a Phase III clinical trial that investigated whether a hyperfractionated radiotherapy (RT) schedule could reduce the risk of locoregional recurrence in patients with locally advanced breast cancer treated with chemotherapy and mastectomy. METHODS AND MATERIALS: Between 1985 and 1989, 200 patients with clinical Stage III noninflammatory breast cancer were enrolled in a prospective study investigating neoadjuvant and adjuvant chemotherapy. Of the 179 patients treated with mastectomy after neoadjuvant chemotherapy, 108 participated in a randomized component of the trial that compared a dose-escalated, hyperfractionated (twice-daily, b.i.d.) chest wall RT schedule (72 Gy in 1.2-Gy b.i.d. fractions) with a once-daily (q.d.) schedule (60 Gy in 2-Gy q.d. fractions). In both arms of the study, the supraclavicular fossa and axillary apex were treated once daily to 50 Gy. The median follow-up period was 15 years. RESULTS: The 15-year actuarial locoregional recurrence rate was 7% for the q.d. arm and 12% for the b.i.d. arm (p=0.36). The rates of severe acute toxicity were similar (4% for q.d. vs. 5% for b.i.d.), but moist desquamation developed in 42% of patients in the b.i.d. arm compared with 28% of the patients in the q.d. arm (p=0.16). The 15-year actuarial rate of severe late RT complications did not differ between the two arms (6% for q.d. vs. 11% for b.i.d., p=0.54). CONCLUSION: Although the sample size of this study was small, we found no evidence that this hyperfractionation schedule of postmastectomy RT offered a clinical advantage. Therefore, we have concluded that it should not be further studied in this cohort of patients.     

Preliminary results of a prospective randomized trial comparing concurrent chemoradiotherapy plus adjuvant chemotherapy with radiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma in endemic regions of china

PURPOSE: A prospective randomized trial was performed to evaluate the efficacy of concurrent chemotherapy and adjuvant chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma (NPC) in endemic regions of China. METHODS AND MATERIALS: Between July 2002 and September 2005, 316 eligible patients were randomly assigned to receive either radiotherapy alone (RT) or chemoradiotherapy concurrent with adjuvant chemotherapy (CRT). All patients received 70 Gy in 7 weeks using standard RT portals and techniques. The CRT patients were given concurrent cisplatin (40 mg/m(2) on Day 1) weekly during RT, followed by cisplatin (80 mg/m(2) on Day 1) and fluorouracil (800 mg/m(2) on Days 1-5) every 4 weeks (Weeks 5, 9, and 13) for three cycles after completion of RT. All patients were analyzed by intent-to-treat analysis. RESULTS: The two groups were well-balanced in all prognostic factors and RT parameters. The CRT group experienced significantly more acute toxicity (62.6% vs. 32%, p = 0.000). A total of 107 patients (68%) and 97 patients (61%) completed all cycles of concurrent chemotherapy and adjuvant chemotherapy, with a median follow-up time of 29 months. The 2-year overall survival rate, failure-free survival rate, distant failure-free survival rate, and locoregional failure-free survival rate for the CRT and RT groups were 89.8% vs. 79.7% (p = 0.003), 84.6% vs. 72.5% (p = 0.001), 86.5% vs. 78.7% (p = 0.024), and 98.0% vs. 91.9% (p = 0.007), respectively. CONCLUSIONS: This trial demonstrated the significant survival benefits of concurrent chemotherapy plus adjuvant chemotherapy in patients with locoregionally advanced NPC in endemic regions of China.     

Intensified hyperfractionated accelerated radiotherapy limits the additional benefit of simultaneous chemotherapy--results of a multicentric randomized German trial in advanced head-and-neck cancer

To demonstrate the efficacy of radiochemotherapy (RCT) as the first choice of treatment for advanced unresectable head-and-neck cancer. To prove an expected benefit of simultaneously given chemotherapy, a two-arm randomized study with hyperfractionated accelerated radiochemotherapy (HF-ACC-RCT) vs. hyperfractionated accelerated radiotherapy (HF-ACC-RT) was initiated. The primary endpoint was 1-year survival with local control (SLC).

Patients with Stage III and IV (UICC) unresectable oro- and hypopharyngeal carcinomas were randomized for HF-ACC-RCT with 2 cycles of 5-FU (600 mg/m²/day)/carboplatinum (70 mg/m²) on days 1–5 and 29–33 (arm A) or HF-ACC-RT alone (arm B). In both arms, there was a second randomization for testing the effect of prophylactically given G-CSF (263 μg, days 15–19) on mucosal toxicity. Total RT dose in both arms was 69.9 Gy in 38 days, with a concomitant boost regimen (weeks 1–3: 1.8 Gy/day, weeks 4 and 5: b.i.d. RT with 1.8 Gy/1.5 Gy). Between July 1995 and May 1999, 263 patients were randomized (median age 56 years; 96% Stage IV tumors, 4% Stage III tumors).

This analysis is based on 240 patients: 113 patients with RCT and 127 patients with RT, qualified for protocol and starting treatment. There were 178 oropharyngeal and 62 hypopharyngeal carcinomas. Treatment was tolerable in both arms, with a higher mucosal toxicity after RCT. Restaging showed comparable nonsignificant different CR + PR rates of 92.4% after RCT and 87.9% after RT (p = 0.29). After a median observed time of 22.3 months, l- and 2-year local-regional control (LRC) rates were 69% and 51% after RCT and 58% and 45% after RT (p = 0.14). There was a significantly better 1-year SLC after RCT (58%) compared with RT (44%, p = 0.05). Patients with oropharyngeal carcinomas showed significantly better SLC after RCT (60%) vs. RT (40%, p = 0.01); the smaller group of hypopharyngeal carcinomas had no statistical benefit of RCT (p = 0.84). For both tumor locations, prophylactically given G-CSF was a poor prognostic factor (Cox regression), and resulted in reduced LRC (log-rank test: ± G-CSF, p = 0.0072).

With accelerated radiotherapy, the efficiency of simultaneously given chemotherapy may be not as high as expected when compared to standard fractionated RT. Oropharyngeal carcinomas showed better LRC after HF-ACC-RCT vs. HF-ACC-RT; hypopharyngeal carcinomas did not. Prophylactic G-CSF resulted in an unexpected reduced local control and should be given in radiotherapy regimen only with strong hematologic indication.     

Postoperative radiotherapy increases locoregional control of patients with stage IIIA non-small-cell lung cancer treated with induction chemotherapy followed by surgery

PURPOSE: To determine the effectiveness of postoperative radiotherapy (RT) in patients with Stage IIB and Stage IIIA non-small-cell lung cancer (NSCLC) treated with induction chemotherapy followed by surgery. METHODS AND MATERIALS: We retrospectively reviewed the treatment records of 98 patients (58 men and 40 women; median age 61 years, range 31-91) with Stage IIB and Stage IIIA NSCLC who were treated with induction chemotherapy followed by surgery at our institution between January 1990 and December 2000. Patients were grouped by treatment (chemotherapy/surgery alone vs. chemotherapy/surgery/RT), by disease stage and nodal classification. The rates of local control (LC), disease-specific survival, disease-free survival, and overall survival (OS) were calculated using the Kaplan-Meier method. RESULTS: Of the 98 patients, 40 had Stage IIB and 58 had Stage IIIA. The clinical disease stage and N stage were significantly greater in those patients who underwent RT than in those who did not; however, no statistically significant differences were identified in the additional characteristics between those receiving and not receiving RT within each stage or nodal group. The overall 5-year actuarial LC rate was 81% in the RT group and 54% in the chemotherapy/surgery-alone group (p = 0.07). Postoperative RT significantly improved the 5-year LC rate in patients with Stage IIIA disease (from 35% to 82%, p = 0.01). Postoperative RT did not significantly improve the 5-year OS rate (30% with RT vs. 49% without) for all patients or for patients with Stage IIIA disease. The disease-specific survival and disease-free survival rates did not differ between the treatment groups. Patients who responded to induction chemotherapy had a significantly greater 5-year OS rate (49%) than did those with stable or progressive disease (22%, p = 0.003). CONCLUSION: Postoperative RT in patients with Stage IIIA NSCLC treated with induction chemotherapy followed by surgery significantly improved LC without improving OS. Significantly improved survival was observed in all patients who responded to induction chemotherapy compared with those with stable or progressive disease.     

Hyperfractionated radiotherapy and concomitant cisplatin for locally advanced laryngeal and hypopharyngeal carcinomas: final results of a single institutional program

SUMMARY: ABSTRACT The purpose of this study was to achieve locoregional control of locally advanced laryngeal carcinoma, survival, and organ preservation using split hyperfractionated accelerated radiation therapy and cisplatin concomitantly. This study was a phase II trial of chemoradiotherapy with split hyperfractionated accelerated radiation therapy, 1.6 Gy per fraction given twice per day to a total dose of 64 to 67.2 Gy for a total of 6 weeks with a 2-week gap, and cisplatin 20 mg/m2, days 1 to 5, in continuous perfusion, concomitantly. Seventy-three patients were treated (stage IV, 64%). At a median follow-up of 55 months for living patients, median survival was 44 months, and 5-year overall survival and disease-free survival were 42% and 39%, respectively. Toxicities included mucositis (grade III, 40%; grade IV, 28%), epithelitis (grade III, 28%). Of the 73 patients, 32 (44%) have continued with their larynx free of disease. Split hyperfractionated accelerated radiation therapy and concomitant cisplatin has been demonstrated to be an active treatment for locally advanced laryngeal carcinomas, but more active combinations of chemotherapy and radiotherapy, without increase of toxicity, are necessary to increase the rate of locoregional control, organ preservation, and survival.     

Final results of the 94-01 French Head and Neck Oncology and Radiotherapy Group randomized trial comparing radiotherapy alone with concomitant radiochemotherapy in advanced-stage oropharynx carcinoma.

PURPOSE: We report the 5-year survival and late toxicity results of a randomized clinical trial, which showed a 3-year improvement in overall survival and locoregional control of stage III or IV oropharynx carcinoma, using concomitant radiochemotherapy (arm B), compared with standard radiotherapy (arm A). PATIENTS AND METHODS: A total of 226 patients were entered onto a phase III multicenter randomized trial comparing radiotherapy alone (70 Gy in 35 fractions; arm A) with concomitant radiochemotherapy (70 Gy in 35 fractions with three cycles of a 4-day regimen comprising carboplatin and fluorouracil; arm B). Prognostic factors were evaluated by univariate and multivariate analysis. Five-year late toxicity was evaluated using National Cancer Institute Common Toxicity Criteria for neurological toxicity, hearing, taste, mandibula, and teeth damage, and Radiation Therapy Oncology Group toxicity criteria for skin, salivary gland, and mucosa. RESULTS: Five-year overall survival, specific disease-free survival, and locoregional control rates were 22% and 16% (log-rank P =.05), 27% and 15% (P =.01), and 48% and 25% (P =.002), in arm B and arm A, respectively. Stage IV, hemoglobin level lower than 125 g/L, and standard treatment were independent prognostic factors of short survival and locoregional failure by univariate and multivariate analysis. One or more grade 3 to 4 complications occurred in 56% of the patients in arm B, compared with 30% in arm A (P was not significant). CONCLUSION: Concomitant radiochemotherapy improved overall survival and locoregional control rates and does not statistically increase severe late morbidity. Anemia was the most important prognostic factor for survival in both arms.     

Efficacy of intensified hyperfractionated and accelerated radiotherapy and concurrent chemotherapy with carboplatin and 5-fluorouracil: updated results of a randomized multicentric trial in advanced head-and-neck cancer

PURPOSE: To prove an expected benefit of concurrent radiochemotherapy (RCT), a two-arm randomized multicentric study was performed. In a subgroup analysis the influence of pretherapeutical hemoglobin level (p-Hb) on survival under locoregional control (SLC) was tested. PATIENTS AND METHODS: The study included primarily untreated Stage III/IV (International Union Against Cancer [UICC]) oropharyngeal and hypopharyngeal carcinomas. Patients were randomized to receive either hyperfractionated (hf) and accelerated (acc) RCT with two cycles 5-fluorouracil (600 mg/m(2)/day) and carboplatin (70 mg/m(2)/day) on Days 1-5 and 29-33 or hf-acc radiotherapy (RT) alone. Total RT dose in both arms was 69.9 Gy in 38 days in concomitant boost technique. RESULTS: After a median follow-up time of 57 months, SLC is significantly better in RCT than in RT (p = 0.01), with median SLC of 17 months and 11 months, respectively. Also overall survival (OS) shows a benefit for RCT (p = 0.016), with a median survival of 23 months for RCT and 16 months for RT. However, the benefit in SLC and OS is not seen in hypopharyngeal carcinomas. In a multivariate analysis of oropharyngeal cancer patients, p-Hb levels lower than 12.7 g/dL resulted in lower SLC compared with higher p-Hb levels up to 13.8 g/dL. P-Hb levels >13.8 g/dL did not further improve SLC. CONCLUSIONS: Hyperfractionated-accelerated RCT is superior to hf-acc RT in oropharyngeal carcinomas. P-Hb levels >13.8 g/dL do not further improve SLC.     

诱导化疗+同期放化疗对局部晚期NSCLC临床价值的Meta分析

目的 应用Meta分析方法评估同期放化疗前加诱导化疗在治疗局部晚期NSCLC中的价值。方法 检索中国生物医学文献数据库、中国学术期刊全文数据库、Cochrane Library、Pubmed、EMbase国内外数据库有关局部晚期NSCLC患者诱导化疗+同期放化疗与同期放化疗对比的文献,依据入选和排除标准收集各项研究的近期疗效及生存情况,应用Meta分析方法评价同期放化疗前加诱导化疗的临床疗效。结果 纳入符合标准的国内外文献5篇,共包括 845例患者。结果显示诱导化疗+同期放化疗较同期放化疗在近期疗效及2、3年生存率方面均相近(OR=0.875,95% CI为 0.507~1.510,P=0.631;HR=0.770,95% CI为 0.515~1.151,P=0.203;HR=0.809,95% CI为 0.559~1.172,P=0.262),但≥3级白细胞下降发生率明显增加(OR=0.637,95% CI为 0.435~0.931,P=0.020)。结论 同期放化疗前加诱导化疗在近期疗效和2、3年生存率并未显示优势,而骨髓抑制明显增加。限于纳入研究较少,病例数偏少,尚需开展多中心随机研究提供更为详实的数据来进一步明确诱导化疗+同期放化疗的临床价值。     

Results of radiotherapy for T2N0 glottic carcinoma: does the "2" stand for twice-daily treatment?

PURPOSE: Radiotherapy (RT) is often the therapy of choice for patients with Stage T2 glottic carcinoma. This retrospective study updated the results of RT for patients treated at our center. The primary focus of this study was whether a policy of using hyperfractionated RT for these patients resulted in a therapeutic gain.METHODS AND MATERIALS: A search of the database of patients treated in the Department of Radiation Oncology at The University of Texas M. D. Anderson Cancer Center was performed to identify patients with Stage T2 glottic carcinoma treated with RT alone between 1970 and 1998. A total of 230 patients formed the study cohort.RESULTS: The median follow-up for all patients was 82 months. Of the 230 patients, 180 were treated with parallel-opposed fields, and the median field size was 30 cm(2). Eighty-one patients (36%) were treated with twice-daily fractionation to 74-80 Gy. Eighty-nine patients (38%) were treated with 32-75 Gy at 2-Gy per fraction once daily, and 57 patients (25%) were treated with 2.06-2.26 Gy, once daily, to 66-70 Gy. The 2- and 5-year actuarial local control rate was 75% and 72%, respectively. After salvage therapy, the ultimate 5-year local control and disease-specific survival rate was 91% and 92%, respectively. The presence of subglottic extension and treatment with a daily dose of < or =2 Gy were associated with poorer local control (p <0.01) on both univariate and multivariate analyses. The 5-year local control rate for patients treated with twice-daily and once-daily RT was 79% and 67%, respectively (p = 0.06).CONCLUSION: The 5-year local control rates with hyperfractionated RT for Stage T2 glottic carcinoma approach 80%. Patients treated with twice-daily fractionation to a median dose of 77 Gy had an improvement in local control compared with patients treated with 70 Gy in 35 fractions. The Radiation Therapy Oncology Group is testing these two fractionation schedules in a randomized study. High control rates were also seen in selected patients treated with hypofractionated schedules, leaving the question of the optimal schedule for patients with Stage T2 disease unanswered.     

Stage I and II aggressive B-cell lymphomas of the head and neck: radiotherapy alone as a treatment option and the usefulness of the new prognostic index B-ALPS

PURPOSE: To evaluate the outcome according to treatment modality and prognostic factors in clinical Stage I and II intermediate- or high-grade B-cell lymphomas of the head and neck. METHODS AND MATERIALS: We analyzed 155 patients treated between 1983 and 1997, excluding those with the Working Formulation low-grade lymphomas. Of these patients, 88 had Stage I and 67 had Stage II disease. Forty-one patients were treated with radiotherapy (RT) alone, and 114 patients were treated with a combination of RT and chemotherapy. Most of the chemotherapy regimens included anthracycline derivatives. More patients with Stage I disease and more patients with poor performance status were treated with RT alone. The treatment results were evaluated according to the new prognostic index B-ALPS, consisting of tumor bulk, age, lactate dehydrogenase level, performance status, and stage. RESULTS: The 5-year overall and failure-free survival rate was 71.5% and 68.3%, respectively, for all 155 patients. The 5-year survival rate was 67% for those treated with RT alone and 73% for those treated with radiochemotherapy (p = 0.13). Among the various potential prognostic factors, age >60 years, World Health Organization performance status 2-4, and tumor size >or=6 cm were associated with poorer survival. The 5-year survival rate was 82% for those with no or one B-ALPS factor, 66% for those with two factors, and 49% for those with three or more factors (p <0.0001). The B-ALPS index appeared to predict the prognosis of these patients better than did the International Prognostic Index. No single prognostic factor was useful to identify patient groups more suitable to treatment with RT alone, but in patients with two B-ALPS risk factors, those treated with radiochemotherapy had a better survival rate and tended to have a better failure-free survival rate than those treated with RT alone. CONCLUSION: A proportion of patients with clinical Stage I or II head-and-neck B-cell lymphoma may be successfully treated with RT alone. B-ALPS is a useful prognostic index in this disease.     

Radiotherapy after radical prostatectomy: does transient androgen suppression improve outcomes?

PURPOSE: The long-term biochemical relapse-free survival and overall survival were compared for patients receiving either radiotherapy (RT) alone or radiotherapy combined with a short-course of total androgen suppression for failure after radical prostatectomy. METHODS AND MATERIALS: Between 1985 and 2001, a total of 122 patients received RT after radical prostatectomy at our institution. Fifty-three of these patients received a short-course of total androgen suppression (TAS) 2 months before and 2 months concurrent with RT with a nonsteroidal antiandrogen and an luteinizing hormone-releasing hormone (LHRH) agonist (combined therapy group); the remaining 69 patients received RT alone. Treatment failure was defined after postoperative RT as a detectable PSA >0.05 ng/mL. Clinical and treatment variables examined included: presurgical PSA, clinical T stage, pathologic Gleason sum (pGS), seminal vesicle (SV) involvement, lymph node involvement, surgical margins, pre-RT PSA, prostate dose, pelvic irradiation, indication for postoperative RT (salvage or adjuvant), and time interval between surgery and RT. Minimum follow-up after postoperative RT was 1 year and median follow-up was 5.9 years (maximum, 14 years) for patients receiving RT alone, and 3.9 years (maximum, 11 years) for patients receiving RT with TAS (combined therapy group). Kaplan-Meier analysis was performed for PSA failure-free survival (bNED) and for overall survival (OS). Cox proportional hazards multivariable analysis examined the influence all clinical and treatment variables predicting for bNED and OS. RESULTS: The median time to PSA failure after postoperative RT was 1.34 years for the combined therapy group and 0.97 years for the RT alone group (p = 0.19), with no failures beyond 5 years. At 5 years, the actuarial bNED rates were 57% for the combined therapy group compared with 31% for the RT alone group (p = 0.0012). Overall survival rates at 5 years were 100% for the combined therapy group compared with 87% for the RT alone group (p = 0.0008). For pGS or=8 the 5-year bNED rates were 65% for combined therapy and 17% for RT alone (p = 0.075). The 5-year OS rates for pGS or=8 was 100% for combined therapy and 54% for RT alone (p = 0.04). On multivariable analysis, only SV involvement (p = 0.0145) and the addition of short-course TAS to postoperative RT (p = 0.0019) were significant covariates predicting for bNED and, similarly, approached significance for overall survival (p = 0.0594 and p = 0.0856, respectively). CONCLUSIONS: Radiotherapy combined with a short-course TAS after radical prostatectomy appears to confer a PSA relapse-free survival advantage and possibly an overall survival advantage when compared with RT alone. The hypothesis that a transient course of androgen suppression with salvage or adjuvant RT after prostatectomy improves outcomes will need to be tested in a randomized trial.     

Accelerated hyperfractionated radiotherapy for cervical cancer: multi-institutional prospective study of forum for nuclear cooperation in Asia among eight Asian countries

PURPOSE: To evaluate the toxicity and efficacy of accelerated hyperfractionated radiotherapy (RT) for locally advanced cervical cancer. METHODS AND MATERIALS: A multi-institutional prospective single-arm study was conducted among eight Asian countries. Between 1999 and 2002, 120 patients (64 with Stage IIB and 56 with Stage IIIB) with squamous cell carcinoma of the cervix were treated with accelerated hyperfractionated RT. External beam RT consisted of 30 Gy to the whole pelvis, 1.5 Gy/fraction twice daily, followed by 20 Gy of pelvic RT with central shielding at a dose of 2-Gy fractions daily. A small bowel displacement device was used with the patient in the prone position. In addition to central shielding RT, intracavitary brachytherapy was started. Acute and late morbidities were graded according to the Radiation Therapy Oncology Group and Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria. RESULTS: The median overall treatment time was 35 days. The median follow-up time for surviving patients was 4.7 years. The 5-year pelvic control and overall survival rate for all patients was 84% and 70%, respectively. The 5-year pelvic control and overall survival rate was 78% and 69% for tumors > or = 6 cm in diameter, respectively. No treatment-related death occurred. Grade 3-4 late toxicities of the small intestine, large intestine, and bladder were observed in 1, 1, and 2 patients, respectively. The 5-year actuarial rate of Grade 3-4 late toxicity at any site was 5%. CONCLUSION: The results of our study have shown that accelerated hyperfractionated RT achieved sufficient pelvic control and survival without increasing severe toxicity. This treatment could be feasible in those Asian countries where chemoradiotherapy is not available.     

Locoregional recurrence of breast cancer: a retrospective comparison of irradiation alone versus irradiation and systemic therapy.

The role of systemic therapy in addition to irradiation for locoregional recurrence of breast cancer is controversial. In the absence of prospective randomized trials, treatment decisions must be based on retrospective studies. We retrospectively analyzed 230 patients treated for locoregionally recurrent breast cancer between 1964 and 1986. Forty-seven were premenopausal, 173 were postmenopausal, and the menopausal status was unknown in 10 patients. Each patient treated with radiotherapy (RT) and chemotherapy or with RT and hormonal therapy was matched with a control patient treated with RT alone. The addition of hormonal therapy to radiation therapy significantly improved the 5-year overall survival (50 versus 28%), disease-free survival (37 versus 26%), and distant metastases-free survival (45 versus 29%). No improvement in locoregional control was observed. In contrast, chemotherapy did not confer such survival benefits, but there was a trend towards improvement in 5-year locoregional control (68 versus 50%), p = 0.08. Our data support the use of hormonal therapy along with RT at the time of locoregional recurrence of breast cancer. Although our data suggest that chemotherapy is not routinely indicated, controlled clinical trials are needed to define which subsets of patients, if any, benefit from systemic therapy.     

Late-course accelerated hyperfractionated radiotherapy for localized esophageal carcinoma

PURPOSE: To evaluate the long-term survival results and patterns of failure for localized carcinoma of the esophagus receiving late-course accelerated hyperfractionated (LCAF) radiotherapy (RT). METHODS AND MATERIALS: We studied 201 patients with histologically confirmed squamous cell carcinoma of the esophagus who were treated with LCAF RT between August 1994 and January 2000. The design of the radiation fields was based on the diagnosis by computed tomography and barium examination. All patients received conventionally fractionated RT at 1.8 Gy/d, five fractions weekly for the first two-thirds of treatment to a dose of about 41.4 Gy in 23 fractions within 4-5 weeks. This was followed by LCAF RT using reduced fields, 1.5 Gy/fraction twice daily with a 6-h interval between fractions, to a dose of about 27 Gy within 9 days. Thus, the total dose was 68.4 Gy in 41 fractions within 44 days. RESULTS: The incidence of Grade 3-5 acute radiation-induced bronchitis was 4.0% (8 cases), 3.0% (6 cases), and 0%, respectively. The incidence of Grade 3-5 acute radiation-induced esophagitis was 14.9% (30 cases), 0.5% (1 case), and 0%. Ten patients (5%) died of late complications. The 1-year, 3-year, and 5-year overall survival rate was 73%, 34%, and 26%, respectively. The 1-year, 3-year, and 5-year local control rate was 77%, 58%, and 56%, respectively. The main site of first failure was locoregional failure and distant metastasis (including lymph node metastasis from regional recurrence). Of 201 patients, 77 (38.4%) had local disease alone or with distant metastasis as the first failure, and 70 patients (34.9%) had distant metastasis and/or lymph node metastasis alone or with local failure as the first failure. CONCLUSION: The LCAF regimen offers similar local control and survival to standard chemotherapy plus RT, such as was delivered in the Radiation Therapy Oncology Group studies 85-01 and 94-05.     

两种非常规分割放疗治疗鼻咽癌的疗效分析

目的 对比观察两种放疗方式治疗鼻咽癌的局部控制率及急性反应和晚期损伤。方法 60例NO-2患者随机分为两组,一组采用标准超分割(HFR)方式放疗,总量DT 76.8 Gy;另一组采用前后程加速超分割(AHFR)方式放疗,总量DT72～75 Gy。结果 (1)两组的5年总生存率和5年无病生存率分别为69.84％、65.86％和62.86％、55.35％。两组的局部控制率均为93.33％。(2)AHFR组与HFR组的急性黏膜反应程度相似,AHRF组略高于HFR组。晚期反应两组无明显差异。(3)放疗结束时局部肿瘤的近期消退率AHFR组低于HFR组。半年时两者CT消退率相同。结论 两种放疗方式无明显差异,标准超分割放疗方式更简便易行。     

Radiotherapy Alone vs. Radiochemotherapy in Patients With Favorable Prognosis of Clinical Stage IIIA Non–Small-Cell Lung Cancer

PurposeTo evaluate the outcome of radiotherapy (RT) vs. radiochemotherapy (RT-CHT) in patients with locally advanced, inoperable non–small-cell lung cancer who had a “favorable” prognosis (stage IIIA, Karnofsky performance score 70-100, no weight loss >5%).Patients and MethodsA total of 222 patients with these characteristics were among 600 patients enrolled into 5 prospective trials between 1988 and 1998, and were treated with either hyperfractionated RT alone (doses of 69.6 and 67.6 Gy when using 1.2 and 1.3 Gy twice a day, respectively) (n = 45) or the same hyperfractionated RT and concurrent CHT (n = 177), which consists of either carboplatin-etoposide (or paclitaxel-carboplatin.ResultsThe median times and 5-year overall survival, local progression-free survival, and the distant metastasis-free survival rates for all 222 patients were 33 months, 31 months, and not attained yet, respectively, and 36%, 43%, and 57%, respectively. RT-CHT was superior to RT alone in terms of both overall survival (median survival time, 38 vs. 21 months, respectively; 5-year, 41% vs. 16%, respectively; P < .001) and local progression-free survival (median time to local progression, 38 vs. 22 months, respectively, 5-year local progression-free survival, 48% vs. 23%, respectively; P < .001) but not the distant metastasis-free survival. The most frequent acute high-grade (>3) toxicity was esophageal and bronchopulmonary (8% each) and the most frequent late high-grade toxicity was esophageal (6%). RT-CHT caused only significantly more hematologic high-grade toxicity.ConclusionsRT-CHT achieved excellent results in this favorable patient population (median survival time, 38 months; 5-year survival, 41%) accompanied with very low toxicity. These results compare favorably with results of other similar studies when using combined RT and CHT, with or without surgery.