Early experience with a hybrid accelerated radiotherapy schedule for locally advanced head and neck cancer

BACKGROUND: Our aim was to determine feasibility and efficacy of a hybrid radiotherapy schedule in locally advanced head and neck cancer. METHODS: Seventy-three patients with locally advanced head and neck cancer were irradiated according to a hybrid accelerated schedule consisting of 20 fractions of 2 Gy (once daily), followed by 20 fractions of 1.6 Gy (twice daily), to a total dose of 72 Gy. RESULTS: Locoregional control was 55% after 2 years. Overall survival was 59%, disease-specific survival was 63%, and disease-free survival was 46%. Acute toxicity was prospectively scored in all 73 patients: the most frequent toxicities were mucositis (50.7%, grade 3), dysphagia (47.9%, grade 3), and dermatitis (34.5%, grade 3). All patients were treated to full dose, without treatment interruption. CONCLUSION: With this regimen, acceptable locoregional control and survival rates are achieved. Toxicity was well manageable, suggesting that a combination of this schedule with concomitant chemotherapy is possible and could lead to further improvement in the treatment of locally advanced head and neck cancer.     

Positive surgical margins in neck dissection specimens in patients with head and neck squamous cell carcinoma and the effect of radiotherapy

BACKGROUND: To evaluate the outcome after surgery and radiotherapy for extensive nodal disease in patients with primary head and neck cancer. METHODS: Between 1973 and 1995, 77 from a total of 1398 patients had histopathologic evidence of positive margins in 85 neck dissection specimens for squamous cell carcinoma of the oral cavity, oropharynx, larynx, or hypopharynx. Postoperative radiotherapy with a curative dose was given to 50 necks. Ipsilateral neck recurrence was defined as the relevant event, and cumulative survival distributions were estimated by the Kaplan-Meier method. Differences between groups were analyzed with the log rank test. RESULTS: Disease-free survival was 24.9% at 2 years, and disease-specific survival was 33.6% at 2 years. After restriction of the 50 patients who received postoperative curative radiotherapy, the time to neck recurrence was stratified according to irradiation dosage, with 62.5 Gy as the cutoff point. A statistically significant difference was found for patients treated with 62.5 Gy or more, with a regional control rate of 75.6% at 2 years (p <.036). CONCLUSIONS: The overall outcome after neck dissection with positive surgical margins is poor. Considerable improvement is achieved by postoperative radiotherapy treatment with dosages of 62.5 Gy or more.     

50例晚期胰腺癌三维适形放疗的近期疗效分析

目的 分析三维适形放疗治疗晚期胰腺癌的疗效及相关预后因素.方法 50例不能手术的晚期胰腺癌病人,采用常规分割的三维适形放疗;其中14例采用姑息性放疗(A组),给予10.8～56 Gy;27例采用单一三维适形放疗(B组),剂量范围为8～60.5 Gy;9例采用同步放化疗的方法(C组),剂量范围为10～64 Gy.同步放化疗中化疗采用吉西他滨(200～600 mg/m~2,1次/周).结果 随访时间为3～35个月,死亡43例,死亡原因主要为肝脏和(或)腹腔内的广泛转移、恶液质、继发感染和出血.存活7例中3例为同步放化疗,3例为单一放疗,1例为姑息治疗.A组存活1人,放疗后局部症状缓解率46%(6/13),平均生存时间5.07个月;其中放疗剂量小于45 Gy的病人有10例,平均存活时间为4.33个月;放疗剂量≥45 Gy者3例,平均存活时间为7.33个月.B组存活3例,治疗后疼痛缓解率为81%(22/27),平均存活6.65个月,其中放疗剂量小于45 Gy的有11例,平均存活时间为4.36个月;放疗剂量≥45 Gy者16例,平均存活时间为8.33个月.C组存活3例,治疗后疼痛缓解率为89%(8/9),放疔后平均存活9.89个月,其中放疗剂量小于45 Gy的有1例,存活时间为3个月;放疗剂量≥45 Gy者8例,平均存活时间为10.73个月.结论 三维适形放疗对晚期胰腺癌有姑息治疗的作用,疗效与治疗方式的选择、放疗剂量、病变累及范围和病人一般状态密切相关.对于部分晚期胰腺癌病人,采用积极同步放化三维适形放疗可获得较长的生存时间.     

The integrated radiosurgical treatment of rectal cancer

The value of radio-surgical protocols in the treatment of advanced rectal cancer has been studied retrospectively. 21 patients operated between 1986 and 1990 fulfilling some criteria were considered for this study. They were 9 men and 12 women with rectal cancer Duke's stage B2-C; 16 were treated with preoperative radiotherapy (30-35 Gy), 5 were treated with postoperative radiotherapy (40-60 Gy). The operative procedures were 12 anterior resections and 9 Miles operations. The 5 years results were: a) cancer free survival 52%; 2 patients alive with relapse; 2 patients with non cancer related death (DIC, radiation enteritis); d) cancer related deaths 28%; e) local recurrence was observed (3 pts) only in association with metastatic disease; f) no isolated local recurrence was observed. Preoperative radiotherapy with 30-35 Gy is judged the preferred protocol for decreasing the rate of isolated local recurrence and for increasing the survival rate. Omental flap transposition plays an important role in the radio-surgical treatment of advanced rectal cancer.     

Management of stage II (T2N0M0) glottic carcinoma by radiotherapy and conservation surgery

BACKGROUND: The best therapeutic approach for the treatment of stage II (T2N0M0) glottic carcinoma is controversial. METHODS: A retrospective tumor registry data retrieval of patients with stage II glottic carcinoma treated with curative intent at Washington University Medical Center-Barnes Hospital between January 1971 and December 1989 (surgery) and December 1995 (radiotherapy) was performed. RESULTS: Among 134 patients with stage II glottic carcinomas treated with curative intent and function preservation, there were 47 patients treated with low dose radiotherapy (median dose, 58.5 Gy at 1.5-1.8 Gy daily fractions), 16 patients with high dose radiotherapy (67.5-70 Gy) at higher daily fractionation doses (2-2.25 Gy), and 71 patients underwent conservation surgery. The overall local control rate was 85%. The overall salvage rate was 68%. The 5-year actuarial and disease specific survivals were 81.5% and 92%, respectively. Unaided phonation was achieved in 84.4% of the patients. An incidence of 10.4% regional metastases, 2.2% distant metastases, and 6% second primary tumors was documented. There were no statistical differences in local control, voice preservation, and 5-year actuarial and disease specific cure rates between conservation surgery and high dose radiation (p = .89). Low dose radiation had statistically lower local controls, 5-year survival, and voice preservation (p = .014). In advanced T2B disease, treating the ipsilateral neck nodes reduced regional metastases (p = .02). CONCLUSIONS: High dose and daily fractionation (70 Gy at 2 Gy daily fraction doses) radiation achieved results equivalent to those of conservation surgery in 5-year local control, survival, and voice preservation. In advanced T2B disease, treatment of the ipsilateral neck nodes by radiotherapy or functional neck dissection reduced regional metastases.     

Pilot trial of concomitant chemotherapy with paclitaxel and split-course radiotherapy for very advanced squamous cell carcinoma of head and neck

PURPOSE: The combination of chemotherapy and irradiation is considered the standard of care for the treatment of advanced squamous cell carcinoma of head and neck (SCCHN). Paclitaxel has shown a single-agent activity in SCCHN. Besides, this drug is a promising radiosensitizer for some human solid tumors. This is a phase II trial to evaluate the feasibility, efficacy, and toxicity of paclitaxel administered concurrently with split-course radiotherapy in advanced unresectable SCCHN. Methods and Materials Thirty-one patients with advanced SCCHN were enrolled in this trial. Radiotherapy consisted of 66 to 70 Gy delivered over 8 to 10 weeks to the primary tumor and lymphatic drainage, with a fractionation scheme of 1.8 to 2 Gy/field/d. After the initial five patients were treated, a 1-week treatment break was introduced. Paclitaxel was administered weekly in a 1-hour intravenous infusion at a projected dosage of 45 mg/m(2)/wk. RESULTS: The complete and partial response rates, based on a 4-week postradiation evaluation were 43.3% and 40%, respectively, with an overall response rate of 83.3%. Median survival was 49.4 weeks, and 1-year survival was 48%. Freedom from local progression was 65.6% at 1 year. Thirty-six percent and 20% of the patients are alive and disease free at 1 and 2 years, respectively. Grade 3/4 of acute toxicity consisted mostly of mucositis, cutaneous reaction, and weight loss. CONCLUSIONS: Paclitaxel concurrent with radiotherapy seems to be active in squamous cell carcinoma of the head and neck. In the regimen selected for this trial, toxicity was significant and led to a prolongation of treatment time.     

Disease control, survival, and functional outcome after multimodal treatment for advanced-stage tongue base cancer

BACKGROUND: Surgical resection and postoperative radiation for advanced-stage malignancies of the oral cavity, oropharynx, and hypopharynx result in a dismal overall survival of 38%. Patients with carcinoma of the tongue base frequently have advanced disease at the time of presentation, and combined-modality therapy is usually required to achieve cure. Because of the poor survival rates with advanced malignancies with standard therapy, new and innovative approaches continue to be developed in an attempt to have a greater impact on disease control, patient survival, and functional outcome after therapy. This study examines functional outcome, survival, and disease control in patients receiving an intensified treatment regimen with concomitant chemoradiotherapy, surgery, and intraoperative radiotherapy for previously untreated, resectable, stage III and IV squamous cell carcinoma (SCC) of the tongue base. METHODS: Forty patients with previously untreated, resectable, stage III and IV squamous cell carcinoma of the tongue base were treated in one of three sequential phase II intensification regimens (IRs). Treatment consisted of perioperative, hyperfractionated radiotherapy (9.1 Gy) with concurrent cisplatin followed by surgical resection with intraoperative radiotherapy boost (7.5 Gy). Postoperative treatment involved concurrent chemoradiotherapy (40 Gy to the primary site and upper neck and 45 Gy to the supraclavicular areas) with cisplatin with or without paclitaxel. Locoregional and distant disease control, 2-year overall, and disease-specific survival rates were calculated. The Performance Status Scale (PSS) for Head and Neck Cancer Patients was administered to 25 of the surviving patients. The effects of the method of surgical reconstruction, surgery involving the mandible and/or larynx, and early versus advanced T stage on PSS score were evaluated with the Wilcoxon rank-sum test. RESULTS: Median follow-up in months for IR1, IR2, and IR3 were 83.6, 75.2, and 26.8. The locoregional control rate was 100%, and the rate of distant metastases was 7.5% for all patients. Two-year overall and disease-specific survival rates for the entire study population were 74.7% and 93.6%, respectively. Mean PSS scores by subscales Eating in Public, Understandability of Speech, and Normalcy of Diet were 55 (range, 0-100), 73 (range, 25-100), and 49 (range, 0-100), respectively. PSS scores were significantly higher in patients with primary closure of the surgical defect, no mandibular surgery, and early T-stage lesions. CONCLUSIONS: Although functional outcome may be decreased by certain surgical interventions and advanced T stage, the high rate of locoregional and distant disease control and excellent 2-year disease-specific survival supports an aggressive treatment regimen for advanced tongue base cancer.     

Intraoperative radiotherapy for head and neck and skull base cancer

BACKGROUND: The purpose of this study was to evaluate the use of intraoperative electron beam radiotherapy (IORT) as an adjuvant modality in the treatment of advanced head and neck and skull base cancer. METHODS: Between 1991 and 1996, 34 patients with squamous cell carcinoma (SCCA) and 10 patients with non-SCCA were enrolled in this prospective nonrandomized clinical trial. Most patients had been previously treated with combinations of surgery, external beam radiotherapy, and chemotherapy. The most frequent sites treated were the skull base (56%) and the neck (44%). IORT was delivered in a dedicated operating room suite with energies of 6 to 15 MeV (6 MeV most commonly used) at doses of 12.5 to 22.5 Gy. RESULTS: At 2 years overall and disease-free survival was 32% and 21%, respectively, for the SCCA patients and 50% and 40%, respectively, for the non-SCCA patients. Tumor control rates at 2 years in the IORT field were 46% for the SCCA patients and 52% for the non-SCCA patients. For squamous cell histology, survival in patients with microscopic residual tumor did not differ from those with no residual tumor, but they both had significantly longer disease-free survival than those patients with gross residual at the time of IORT (p =.03), with a trend toward longer overall survival (p =.09). The only complication directly attributable to IORT was a neuropathy in a patient who received an IORT dose of 22.5 Gy (cumulative dose 130.1 Gy). CONCLUSIONS: IORT at a dose of 12.5 Gy is safe and produces tumor control and survival for patients likely to have microscopic residual disease in sites difficult to resect such as the skull base.     

Neck dissection and ipsilateral radiotherapy in the management of cervical metastatic carcinoma from an unknown primary

BACKGROUND: In a small proportion of patients presenting with metastases to cervical lymph nodes the primary cancer remains occult despite thorough evaluation. The present report examines patterns of failure and outcome following an initial treatment strategy directed principally at the clinically involved side of the neck. METHODS: From a prospectively compiled computerized database 38 patients were identified with metastatic squamous cell carcinoma from an occult primary site. These patients were evaluated with respect to initial treatment, subsequent detection of a primary tumour, neck recurrence and survival characteristics. RESULTS: Thirty-seven of 38 patients were treated with curative intent and all had neck dissection. Adjuvant radiotherapy was given to 34 of the 37 (90%; 32 postoperatively and two pre-operatively). Radiotherapy was directed at the ipsilateral neck alone in 24 patients while 10 received comprehensive treatment to both sides of the neck and potential occult primary sites. The rate of control of disease in the ipsilateral neck was 91% while the failure rate in the contralateral neck was 16% (six patients). A primary cancer was ultimately identified in five patients (13%). Disease-specific survival was 63% at 4 years. Clinical N3 stage, extracapsular tumour extension and involved surgical margins predicted for poorer survival on univariate analysis. Analysis using multiple risk factors found that only involved surgical margins predicted for treatment failure. CONCLUSIONS: Despite generally advanced disease at presentation, patients presenting with cervical metastasis from an unknown primary carcinoma have a reasonable survival expectation and aggressive treatment is warranted, but approximately half will develop recurrent disease. Careful follow-up is required if effective salvage treatment is to be instituted.     

Metastatic squamous cell carcinoma of the neck from an unknown primary: management options and patterns of relapse

PURPOSE: Management of squamous cell carcinoma of undetermined primary tumors in the head and neck region is controversial. Here we report the Southern California Kaiser Permanente experience with these patients. METHODS AND MATERIALS: From January 1969 through December 1994, 106 patients were eligible for this retrospective analysis. Distribution of nodal staging was as follows: 14 N1, 27 N2A, 39 N2B, 2 N2C, and 24 N3. Initial treatment included excisional biopsy alone in 12, radical neck dissection alone in 29, radiotherapy alone in 24, excisional biopsy followed by radiotherapy in 15, and radical neck dissection plus postoperative radiation in 26 patients. RESULTS: Except for two patients, all patients have had a minimum follow-up of 5 years. Overall, 57 patients (54%) have had recurrences. Only two patients (3%) who had received radiotherapy as part of their initial treatment had an appearance of a potential primary site inside the irradiated field vs 13 patients (32%) who had not received radiotherapy (p =.006). Combined modality therapy resulted in fewer neck relapses, particularly in patients with advanced neck disease. Including salvage, surgery alone as the initial treatment resulted in 81% ultimate tumor control above the clavicle for patients with N1 and N2a disease without extracapsular extension. The 5-year survival for the entire population was 53%. Radiotherapy alone resulted in poor survival in patients with advanced/unresectable neck disease. No significant difference in survival based on the initial treatment was found. The statistically significant adverse factors in determining survival included advanced nodal stage and the presence of extracapsular extension. CONCLUSIONS: Radiotherapy is very effective in reducing the rate of appearance of a potential primary site. However, in the absence of advanced neck disease (N1 and N2A without extracapsular extension), radiotherapy can be reserved for salvage. Radiotherapy alone results in poor outcomes in patients with advanced/unresectable neck disease, and incorporation of concurrent chemotherapy and cytoprotective agents should be investigated.     

直肠癌术后局部复发综合治疗的疗效分析

目的：分析直肠癌根治术后局部复发的类型、综合治疗的疗效及预后。方法：对直肠癌术后局部复发、以往未接受过放疗的66例病人进行疗效分析。原手术方式为经腹直肠切除术45例(Dixon术40例，Parks术5例)，腹会阴直肠切除术21例。经腹直肠切除术后复发以吻合口为主(37／45，82．2％)，腹会阴直肠切除术后复发则以盆腔或会阴为主(19／21，90．5％)。复发后盆腔放疗中位剂量为40(20—64）Gy，临床症状缓解中位剂量26(10～52)Gy。其中26例在放疗过程中或之后接受过中位7个(2～12)疗程以5-FU为主的化疗。有22例放疗后获补救手术机会。结果：全组中位生存期24个月。Kaplan-Merier法计算生存率，放疗后1、3年总生存率分别为72．2％、17．9％。单因素分析并Log rank检验生存率差异，显示生存率与原发病变的期别、术后复发时间、复发部位及是否加用化疗无关，而仅与是否再次行补救手术有关。放疗后加用补救手术者3年生存期明显较长，为36．0％比8．8％(P=0．016)。结论：直肠癌根治术后局部复发者，放疗具有良好的姑息减症的作用；对部分经腹直肠切除术后的复发病例，放射治疗加补救手术能明显延长生存期。     

Benefit of postoperative chemoradiotherapy for patients with unknown primary squamous cell carcinoma of the head and neck

BACKGROUND: Postopertative adjuvant chemoradiotherapy recently became an established modality for patients with selected high-risk locally advanced head and neck cancers. The optimal treatment of unknown primary squamous cell cancer of the head and neck (SCCHN) continues to be controversial, since major randomized studies excluded those patients. METHODS: We conducted a retrospective review of patients treated during 1995 to 2002 for unknown primary SCCHN. All patients were treated with a neck dissection followed by concurrent high-dose cisplatin (100 mg/m(2)) and bilateral neck radiotherapy. RESULTS: Thirty-seven patients were identified with nodal disease distribution of N1 (5%), N2a (22%), N2b (41%), N2c (8%), N3 (22%), and Nx (3%). Modified neck dissection was done on the majority (30/37 = 81%) of patients. With a median follow-up of 42 months among the survivors, very few patients had regional recurrence (5%) or distant failure (11%), and 89% of patients were alive. The actuarial 5-year overall survival rate could not be estimated because there were no deaths beyond 20 months after surgery. Substantial yet acceptable acute and late morbidities were demonstrated in this cohort of patients. CONCLUSIONS: Postoperative chemoradiotherapy is of potential benefit to patients with unknown primary SCCHN by improving survival and reducing failures. This treatment warrants further prospective evaluation.     

Adjuvant chemotherapy in T3 carcinoma of the bladder. A prospective trial: preliminary report

We report the early results of a multi-centre, randomised prospective trial of neoadjuvant and maintenance chemotherapy with methotrexate (MTX) in 376 patients with advanced (T3) carcinoma of the bladder. In patients under 65 years of age, treatment consisted of radical radiotherapy (64 Gy) or, in some centres, pre-operative radiotherapy (44 Gy) and elective cystectomy. All patients over 65 had radical radiotherapy. MTX was administered to 188 patients. There was no increase in toxicity attributable to the MTX. MTX did not significantly increase the proportion of patients whose tumours responded to radiotherapy; 50% (70/141) responded to radiotherapy and 56% (76/136) to MTX radiotherapy. The development of metastases and survival was also similar in both groups (3-year survival: radiotherapy 37.3%, MTX + radiotherapy 38.6%). We report the logistic difficulties of the administration of prolonged courses of maintenance chemotherapy. Further controlled trials of neo-adjuvant chemotherapy in advanced bladder cancer are required, involving more active regimes.     

Metastatic carcinoma to the cervical nodes from an unknown head and neck primary site: Is there a need for neck dissection?

BACKGROUND: The aim of the study was to evaluate the outcomes and patterns of failure in patients with metastatic carcinoma to cervical lymph nodes from an unknown head and neck primary origin, who were treated curatively with radiotherapy, with or without neck dissection. METHODS: The study included 61 patients referred to the McGill University Hospital Centers from 1987 to 2002. The median age was 57 years, with male to female ratio of 4:1. Distribution of patients by N status was as follows: N1, 16 patients (26%); N2a, 18 (30%); N2b, 13 (22%); N2c, 7 (11%); and N3, 7 (11%). Twenty patients underwent neck dissection (11 radical, 9 functional) and 41 patients had biopsy (9 fine-needle aspiration and 32 excisional biopsy). All patients received radiotherapy. The median dose to the involved node(s) was 64 Gy, and 60 Gy to the rest of the neck. Treatment of the neck was bilateral in 50 patients (82%) and ipsilateral in 11 (18%). The minimum duration of the follow-up was 12 months, with the median of 32 months. RESULTS: The 5- and 8-year overall survival for the whole population was 79% and 67%, respectively. There was no statistically significant difference in the 8-year actuarial overall survival (64.8% and 67.6%, respectively, p = .64) and local relapse-free survival (75% vs 74.5%, respectively, p = .57), among patients who had biopsy versus those who had neck dissection. CONCLUSION: In our experience, definitive radiotherapy to the neck and the potential mucosal sites, whether preceded by neck dissection or not, is effective to achieve a good local control rate in the unknown primary cancer of the head and neck. The indication for neck dissection, in particular for early nodal stage, is controversial.     

Surgical resection is necessary to maximize tumor control in function-preserving, aggressive chemoradiation protocols for advanced squamous cancer of the head and neck (stage III and IV)

Background:The role of surgery in aggressive chemoradiation protocols for advanced head and neck cancer has been questioned because of the quoted high clinical response rates in many series.Methods:The role of surgical resection was examined in an aggressive neoadjuvant protocol of weekly paclitaxel, carboplatin, and radiation for stage III and IV with completion of radiation to 72 Gy if biopsy at the primary site was negative after administration of 45 Gy. Of 43 patients enrolled, 38 completed the protocol. The clinical response was 100% (including 18 complete and 20 partial responses).Results:The complete pathologic response (negative primary site biopsy at 45 Gy) was 25 of 38 (66%). Of patients who presented with N1 to N3 nodes, neck dissection revealed residual nodal metastases in 22%. Surgical resection of the primary site was required in 13 patients, including 5 with larynx cancer and 2 with base of tongue cancers. Four patients had resection with reconstruction for advanced mandible floor of mouth cancer, and one had resection of nasal-maxillary cancer. Functional resection was performed in 9 of 12 patients. The median progression free and overall survival was 64% and 68%, respectively, at median follow-up of 50 months. Nine patients developed recurrence (three local and six distant). There were no failures in the neck. Salvage surgery was performed in one patient with local and one with distant disease.Conclusions:Surgical resection is an essential component of aggressive chemoradiation protocols to ensure tumor control at the primary site and in the neck.     

Interstitial high-dose-rate brachytherapy combined with cervical dissection on head and neck cancer

BACKGROUND: The literature is scarce regarding the use of interstitial high-dose-rate brachytherapy (I-HDR) as adjuvant treatment of the cervical region, and most reports are focused on primary tumors of the mobile tongue and oropharynx. We evaluated the outcome and morbidity related to an institutional treatment policy, using I-HDR as the sole adjuvant treatment or in combination with external beam radiotherapy (EBRT) at the Departments of Radiation Oncology and Head and Neck Surgery, Hospital do Cancer, Sao Paulo, Brazil. METHODS: From October 1994 to December 2003, charts of 42 patients who had biopsy-proven cervical head and neck cancer, with a median follow-up of 36 months (range, 8-111 months), were reviewed. The median age of the patients was 55 years (range, 31-76 years), and the male/female ratio was 4.25:1.00. Thirty-five patients had previous irradiation with EBRT, with doses ranging from 30 Gy to 65 Gy (median, 52 Gy). The total dose of I-HDR ranged from 12 Gy to 48 Gy (median, 24 Gy), given in three to 14 fractions (median, 6 fractions) in 2 to 8 days (median, 4 days). RESULTS: The total treatment time ranged from 19 to 83 days (median, 35 days). The 5- and 8-year overall survival (OS) rates were 52.5% and 48.1%, respectively; and the relapse-free survival (RFS) rates were 48.5% and 38.1%, respectively. The only statistically significant prognostic factor for RFS and OS at 5 and 8 years was margin status (p = .0050). Four patients (9.5%) had late adverse side effects, such as local dehiscence (n = 2), local ulcer (n = 1), and extensive neck fibrosis (n = 1), not related to a higher dose to the skin or graft. CONCLUSION: These results suggest that I-HDR can be recommended in selected patients with first presentation lesions, local recurrences, or second primary carcinomas, even with a previous course of EBRT, but further studies are eagerly awaited to delineate the optimum schedule for this combination-treatment modality.     

Planned neck dissection as an adjunct to the management of patients with advanced neck disease treated with definitive radiotherapy: for some or for all?

BACKGROUND: Management of patients with head and neck carcinoma and advanced nodal disease is controversial. The purpose of this analysis was to evaluate the efficacy and toxicity of definitive radiotherapy followed by planned neck dissection in patients with bulky neck disease. MATERIALS AND METHODS: The records of 52 patients who were treated between 1989 and 1995 at the Peter MacCallum Cancer Institute with a planned neck dissection after radical radiotherapy were reviewed. All had advanced neck disease with one or more nodes >/=3 cm in maximum diameter, 94% being staged N2-3. The most common primary site was the oropharynx (56%). Sixty percent of patients had either T2 or T3 primaries and all were AJCC stage IV. Treatment consisted of high-dose radiotherapy to the primary and involved neck sites using various fractionation protocols followed by radical or modified radical neck dissection after confirmation of a complete response at the primary site. The median follow-up for living patients was 58 months (range 32-97). RESULTS: There were nine regional failures, of which three were outside the dissected neck, yielding a 5-year actuarial overall neck control rate of 83% and an in-field control rate of 88%. In-field control rates by neck stage were N1 3/3; N2 31/35; N3 11/13 and NX 1/1. There was only one in-field failure among 28 patients who had pathologically negative neck specimens compared with five in 24 patients with morphologic evidence of residual disease. Of the 24 patients with pathologically positive necks, 5 were long-term survivors and were probably cured by their surgery. Another 4 died of intercurrent disease without documented recurrence of their head and neck cancer. Ten patients recurred at their primary sites (5-year actuarial control 79%) and 8 developed distant metastases (5-year actuarial rate 20%). A total of 21 patients failed at one or more sites and none was salvaged. Five-year actuarial disease-free survival was 57% and overall survival 38%. Nine patients (17%) sustained significant complications following neck dissection. CONCLUSIONS: In patients with advanced neck disease who are treated primarily with radical radiotherapy, planned neck dissection provides excellent regional control and appears to cure a subset of patients. However, routine neck dissection adds significant morbidity to treatment and should ideally be avoided in those patients in whom surgery is either unnecessary (no residual tumor) or futile (unsalvageable disease recurrence outside the dissected neck). Based on our analysis and other recently reported series, we now recommend observing patients who have a complete response to high-dose radiotherapy (+/- chemotherapy). The ability of PET imaging to detect residual viable tumor in the head and neck or at distant sites is under investigation.     

Hyperfractionated accelerated radiotherapy in combination with weekly cisplatin for locally advanced head and neck cancer

BACKGROUND: The purpose of this study was to determine the feasibility and efficacy of hyperfractionated accelerated radiotherapy (HFRCB) combined with simultaneous chemotherapy with weekly cisplatin (CDDP) in locally advanced inoperable head and neck cancer. METHODS: From August 1999 to December 2002, 37 patients (median age, 59 years) with Union Internationale Contre le Cancer stage III (n = 2) and stage IV (n = 35) squamous cell cancer of the oropharynx and hypopharynx were treated in a prospective phase I/II trial. Concomitant boost radiotherapy (1.8 Gy, days 1-38 and 1.5 Gy boost, days 22-38, twice daily with at least a 6-hour interval; total dose 69.9 Gy) and simultaneous cisplatin, 40 mg/m2 weekly, were given. RESULTS: The median treatment duration was 42 days (range, 38-46 days). Toxicity was manageable, with neutropenia grade III/IV and thrombocytopenia grade IV in seven and one patients, and mucositis grade III/ IV in 27 and five patients, respectively. Chemotherapy was restricted to four weekly applications in 29 patients mainly because of mucosal toxicity with a median dose intensity of 160 mg/m2 (0-200) of cisplatin in 5.5 weeks. With a median follow-up of 28 months for living patients, the 2-year overall survival rate was 67%. The median overall and relapse-free survival times were 36 and 31 months, respectively. CONCLUSION: HFRCB in combination with weekly cisplatin achieves a high rate of locoregional control and survival. Four weekly cycles of 40 mg/m2 cisplatin seem to be the dose limit for most patients.     

Postoperative radiotherapy for locally advanced colon cancer

Background: The role of adjuvant postoperative radiotherapy for locally advanced colon cancer is not well documented. Methods: Seventy-eight patients who underwent a complete resection of B2-C colon cancer received postoperative radiotherapy. Twenty-eight patients received ⩽45 Gy; 50 patients received 50–55 Gy. Twenty-seven patients received adjuvant fluorouracil-based chemotherapy. All patients were followed for a minimum of 3 years; no patients were lost to follow-up. Results: The overall local control rate was 88%. The 5-year actuarial rate of local control was 96% after 50–55 Gy postoperative radiotherapy compared with 76% after <50 Gy (p=0.0095). Multivariate analysis of local control showed that only radiotherapy dose significantly influenced this end point. Cause-specific survival rates at 5 years were B2, 67%; B3, 90%; C1, 100%; C2, 61%; C3, 36%; and overall, 63%. Multivariate analysis of cause-specific survival showed that only stage significantly influenced this end point. Bowel obstruction caused by adhesions developed in three patients and required a laparotomy; radiation-induced sarcoma developed in one additional patient. Conclusions: Postoperative radiotherapy appears to reduce the risk of local recurrence in patients with locally advanced colon cancer. The optimal dose is probably 50–55 Gy at 1.8 Gy per fraction. Postoperative radiotherapy may improve cause-specific survival for patients with stages B3 and C2 cancers.