Protective effect of amifostine on dental health after radiotherapy of the head and neck

Purpose: The cytoprotective agent amifostine has been shown to reduce the radiation-induced acute and chronic xerostomia in head and neck cancer patients. The purpose of this study was to evaluate whether or not amifostine also reduces the incidence of dental caries associated with the radiation-induced xerostomia.

Methods and Materials: The dental status before and 1 year after radiotherapy was retrospectively compared in 35 unselected patients treated as part of the prospective randomized and multicenter open-label Phase III study (WR-38) at the University Hospitals of Heidelberg, Freiburg, and Erlangen. The WR-38 study compared radiotherapy in head and neck cancer with and without concomitant administration of amifostine.

Results: Patient and treatment characteristics (particularly the radiation dose and percentage of parotids included in the treatment volume) were equally distributed between the patients who received (n = 17) or did not receive (n = 18) amifostine. Fifteen patients of the amifostine group showed no deterioration of the dental status 1 year after radiotherapy as compared to 7 patients who did not receive the cytoprotector (p = 0.015, two-tailed Fisher exact test).

Conclusion: Our data suggest a protective effect of amifostine on the dental health after radiotherapy of the head and neck. The dental status should be used as a primary endpoint in future studies on amifostine.     

Chemoradiation therapy using radiotherapy, systemic chemotherapy with 5-fluorouracil and nedaplatin, and intra-arterial infusion using carboplatin for locally advanced head and neck cancer - Phase II study

To improve the treatment results for locally advanced head and neck cancer, chemoradiation therapy by radiotherapy, systemic chemotherapy with 5-fluorouracil (5FU) and nedaplatin (NDP), and intra-arterial therapy using carboplatin (CBDCA) was performed. Thirty-two patients were entered into the study between July 1997 and August 2002. According to the TNM staging (1997), 14 patients had stage III lesions, and 19 patients had stage IV (M0) lesions. Alternating chemoradiotherapy was performed by the following regimen. Initially, systemic chemotherapy was administered, followed by 4 weeks of radiotherapy (36 Gy/20 fractions; wide field irradiation) starting 2 days after chemotherapy, a second course of systemic chemotherapy 2 days after radiotherapy, and a second course of a reduced field radiotherapy (30 Gy/15 fractions) 2 days after chemotherapy. Arterial injection therapy was administered in the latter half of radiotherapy after the end of the second course of systemic chemotherapy. For systemic chemotherapy, 5FU at 3500 mg/m²/120 h was intravenously administered for 5 days (Days 1–5), and NDP at 120 mg/m²/6 h was administered on Day 6. An intra-arterial agent using CBDCA was continuously infused by a portable electrical pump for 4 (to 6) weeks. The total dose of CBDCA was AUC 6 as established by Calvert’s formula. The 5-year local control rate was 59%. The 5-year overall survival rate was 51%. There were no clinically significant adverse effects. Chemoradiation therapy by radiotherapy, systemic chemotherapy, and intra-arterial chemotherapy for locally advanced head and neck cancer may be useful for improving treatment results.     

An analysis of the prognostic significance of p53 status for squamous cell carcinoma of the oral cavity treated by radiotherapy

The status of the p53 gene in biopsy specimens was analyzed to determine whether it is predictive of the outcome of radiotherapy of squamous cell carcinomas of the oral cavity. Biopsy materials were obtained from 45 patients, and the p53 status of each patient was determined using a single-strand conformation polymorphism analysis. Fourteen of the patients were treated with radiation therapy alone; the other 31 patients underwent radiotherapy in combination with surgery or chemotherapy. Twenty-seven patients had tumors with wild-type p53 and 18 patients had a tumor with mutant p53. The initial tumor response was not significantly different between these two groups. Kaplan–Meier survival plots (log-rank test) showed that the probability of survival was not significantly different between two groups although the patients with mutant p53 had a tendency for longer survival (P=0.2941). However, among the patients with stage III/IV tumors (n=24), those with a wild-type p53 status tended to have longer survivals.     

乳腺癌患者体重指数及体位固定方式对保乳术后调强放射治疗摆位误差的影响

目的 探讨乳腺癌保乳术后调强放疗中不同体重指数(Body mass index, BMI)患者体位固定方式与摆位误差的相关性。方法 回顾性分析接受调强放疗的117例保乳术后乳腺癌患者的临床资料。根据放疗时患者不同的体位固定方式分为A、B两组,A组患者(57例)为真空袋组,B组患者(60例)为乳腺托架组。根据患者的BMI指数分为1组(<18.5 kg/m²)、2组(18.5～23.9 kg/m²)、3组(24～27.9 kg/m²)和4组(≥28 kg/m²)。比较不同BMI分组的乳腺癌患者体位固定方式与摆位误差的关系。结果 A组患者左右方向(X轴)总摆位误差小于B组(P<0.05);A3、A4组患者X及Y轴摆位误差小于B3、B4组(P<0.05)。在前后方向(Z轴)上,A组和B组之间的差异均无统计学意义(P>0.05)。结论 保乳术后接受调强放射治疗的乳腺癌患者BMI指数对摆位误差具有影响,对于超重患者(BMI≥24 kg/m²)更宜选用真空袋固定方式。     

Effective palliative radiation therapy in advanced and recurrent ovarian carcinoma

Purpose: To retrospectively review our experience using radiation therapy as a palliative treatment in ovarian carcinoma.

Methods and Materials: Eighty patients who received radiation therapy for ovarian carcinoma between 1983 and 1998 were reviewed. The indications for radiation therapy, radiation therapy techniques, details, tolerance, and response were recorded. A complete response required complete resolution of the patient’s symptoms, radiographic findings, palpable mass, or CA-125 level. A partial response required at least 50% resolution of these parameters. The actuarial survival rates from initial diagnosis and from the completion of radiation therapy were calculated.

Results: The median age of the patients was 67 years (range 26 to 90 years). A median of one laparotomy was performed before irradiation. Zero to 20 cycles of a platinum-based chemotherapy regimen were delivered before irradiation (median = 6 cycles). The reasons for palliative treatment were: pain (n = 22), mass (n = 23), obstruction of ureter, rectum, esophagus, or stomach (n = 12), a positive second-look laparotomy (n = 9), ascites (n = 8), vaginal bleeding (n = 6), rectal bleeding (n = 1), lymphedema (n = 3), skin involvement (n = 1), or brain metastases with symptoms (n = 11). Some patients received treatment for more than one indication. Treatment was directed to the abdomen or pelvis in 64 patients, to the brain in 11, and to other sites in 5. The overall response rate was 73%. Twenty-eight percent of the patients experienced a complete response of their symptoms, palpable mass, and/or CA-125 level. Forty-five percent had a partial response. Only 11% suffered progressive disease during therapy that required discontinuation of the treatment. Sixteen percent had stable disease. The duration of the responses and stable disease lasted until death except in 10 patients who experienced recurrence of their symptoms between 1 and 21 months (median = 9 months). The 1-, 2-, 3-, and 5-year actuarial survival rates from diagnosis were 89%, 73%, 42%, and 33%, respectively. The survival rates calculated from the completion of radiotherapy were 39%, 27%, 13%, and 10%, respectively. Five percent of patients experienced Grade 3 diarrhea, vomiting, myelosuppression, or fatigue. Fourteen percent of patients experienced Grade 1 or 2 diarrhea, 19% experienced Grade 1 or 2 nausea and vomiting, and 11% had Grade 1 or 2 myelosuppression.

Conclusions: In this series of radiation therapy for advanced ovarian carcinoma, the response, survival, and tolerance rates compare favorably to those reported for current second- and third-line chemotherapy regimens. Cooperative groups should consider evaluating prospectively the use of radiation therapy before nonplatinum and/or nonpaclitaxel chemotherapy in these patients.     

CT-MRI融合技术在头颈部肿瘤GTV勾画中应用的研究

目的比较CT、MRI和CT-MRI融合技术在头颈肿瘤靶区勾画中的差异,探讨CT-MRI融合技术在头颈肿瘤靶区勾画中的优势。方法 35位头颈部肿瘤患者,通过CT、MRI扫描,利用图像融合软件得到每位患者的两幅图像;同一医生对同一患者在同一时间段内依据CT、MRI和融合图像勾画出靶区,比较原发病灶的肿瘤靶区的体积(Gross tumor volume,GTV)。结果 GTV_CT、GTV_MRI、GTV_CT-MRI的平均值分别为(21.22±1.56)cm³、(23.64±1.30)cm³、(29.08±2.09)cm³,GTV_CT与GTV_MRI比较(t=7.05,P＜0.01),GTV_CT-MRI与GTV_CT比较(t=-17.82,P＜0.01);GTV_CT-MRI与GTV_MRI比较(t=13.08,P＜0.01)。结论 CT-MRI融合图像的头颈部肿瘤勾画靶区比单独MRI或CT图像的头颈部肿瘤勾画靶区更广,CT-MRI融合图像技术可提高靶区勾画的准确性,更利于指导精确放疗的实施。     

A pilot study of topical intrarectal application of amifostine for prevention of late radiation rectal injury

Clinical symptomatic late injury to the rectal wall occurs in about one-third of patients with prostate cancer treated with external beam irradiation. Reducing the physical dose to the anterior rectal wall without a similar reduction in the posterior peripheral zone is difficult because of the proximity of the prostate to the anterior rectal wall. On the basis of our previous observations in an animal model that intrarectal application of amifostine resulted in very high concentrations of amifostine and its active metabolite WR-1065 in the rectal wall, a Phase I dose-escalation clinical trial was undertaken.

Twenty-nine patients with localized prostate cancer were accrued. Eligibility criteria included histologically confirmed adenocarcinoma, Karnofsky performance status ≥70, and no pelvic lymphadenopathy or distant metastases. The total dose to the prostate was 70.2 Gy in 20 patients and 73.8 Gy in 9 patients. Therapy was delivered using a 4-field technique with three-dimensional conformal planning. Amifostine was administered intrarectally as an aqueous solution 30 min before irradiation on the first 15 days of therapy. Amifostine was escalated in cohorts from 500 to 2500 mg. Proctoscopy was performed before therapy and at 9 months after completion. Most patients underwent repeat proctoscopy at 18 months. On Days 1 and 10 of radiotherapy, serum samples were collected for pharmacokinetic studies. The clinical symptoms (Radiation Therapy Oncology Group scale) and a proctoscopy score were assessed during follow-up.

All patients completed therapy with no amifostine-related toxicity at any dose level. The application was feasible and well tolerated. No substantial systemic absorption occurred. With a median follow-up of 26 months, 9 patients (33%) developed rectal bleeding (8 Grade 1, 1 Grade 2). At 9 months, 16 and 3 patients developed Grade 1 and Grade 2 telangiectasia, respectively. This was mostly confined to the anterior rectal wall. No visible mucosal edema, ulcerations, or strictures were noted. No significant differences were found between the proctoscopy findings at 9 and 18 months. Four patients (14%) developed symptoms suggestive of radiation damage that, on sigmoidoscopy, proved to be secondary to unrelated processes. These included preexisting nonspecific proctitis (n = 1), diverticular disease of the sigmoid colon (n = 1), rectal polyp (n = 1), and ulcerative colitis (n = 1). Symptoms developed significantly more often in patients receiving 500–1000 mg than in patients receiving 1500–2500 mg amifostine (7 [50%] of 14 vs. 2 [15%] of 13, p = 0.0325, one-sided chi-square test).

Intrarectal application of amifostine is feasible and well tolerated. Systemic absorption of amifostine and its metabolites is negligible, and close monitoring of patients is not required with rectal administration. Proctoscopy is superior to symptom score as a method of assessing radiation damage of the rectal wall. The preliminary efficacy data are encouraging, and further clinical studies are warranted.     

Supportive use of megestrol acetate (Megace) with head/neck and lung cancer patients receiving radiation therapy

The purpose of this study was to measure the effect of megestrol acetate (MA) on weight loss and quality of life (QOL) in patients with cancer of the lung or head and neck undergoing curative radiation therapy.

This was a Phase III, placebo-controlled, double-blind randomized study. Patients received either 800 mg/day of MA (20 milliliters po qAM) or placebo over a 12-week period. Patients received radiation of the head and neck or thorax using a dose of at least 50 Gy, either alone or with chemotherapy. Weight was assessed weekly, whereas QOL was assessed at baseline and at 4, 8, and 12 weeks.

Patient characteristics on the MA arm (16 lung, 12 head/neck; mean age: 60 years) were similar to those on the placebo arm (17 lung, 11 head/neck; mean age: 65.8 years). Patients in the MA group had a mean weight loss over 12 weeks of 2.7 pounds, whereas the placebo group had a mean weight loss of 10.6 pounds. There was a significant time by treatment interaction (p = 0.001), with the difference in weight between treatment groups being most pronounced after 6 weeks. Although overall QOL was similar in both arms of the study, several QOL subscale items did differ significantly. Compared to the placebo-treated patients, head-and-neck cancer patients in the MA arm reported the ability to eat as much as they liked (p = 0.02 at 12 weeks), and lung cancer patients in the MA arm reported significantly better appetite at 4 weeks (p = 0.03) and 8 weeks (p = 0.001).

MA used prophylactically is useful as an appetite stimulant; it can help patients maintain weight over the course of curative radiotherapy of the head and neck or lung and can improve specific aspects of QOL.     

Local hyperthermia, radiation, and chemotherapy in recurrent breast cancer is feasible and effective except for inflammatory disease

Purpose: To investigate the feasibility and effectiveness of radiochemothermotherapy (triple-modality therapy) in patients with inoperable recurrent breast cancer.

Patients and Methods: Patients with inoperable recurrent lesions, World Health Organization (WHO) performance status of 2 or greater, life expectancy of more than 3 months, adequate bone marrow, hepatic and renal function were eligible for this Phase I/II study. Conventionally fractionated or hyperfractionated radiotherapy (RT) was performed. Once-weekly local hyperthermia (HT) combined with chemotherapy (CT; epirubicin 20 mg/m², ifosfamide 1.5 g/m²) was applied within 30 min after RT.

Results: Twenty-five patients, all heavily pretreated (18/25 preirradiated), received a mean total dose of 49 Gy. The median number of HT/CT sessions was 4. Skin toxicity was low, whereas bone marrow toxicity was significant (leucopenia Grade 3/4 in 14/1 patients). The overall response rate was 80% with a complete response (CR) rate of 44%. Response rates in patients with noninflammatory disease (n = 14; CR 10 patients, partial response [PR] 3 patients) were far better than in patients with inflammatory disease (n = 11; CR 1 patient, PR 6 patients).

Conclusions: In patients with recurrent breast cancer, triple-modality therapy is feasible with acceptable toxicity. High remission rates can be achieved in noninflammatory disease, however, local control is limited to a few months. Whether the addition of chemotherapy has a clear-cut advantage to radiothermotherapy alone remains an open question.     

盐酸帕洛诺司琼与托烷司琼预防含大剂量顺铂方案化疗所致呕吐的疗效

  目的  探讨注射用盐酸帕洛诺司琼在骨肉瘤患者大剂量化疗中预防恶心、呕吐的疗效, 及其不良反应。  方法  80例骨肉瘤患者接受大剂量顺铂(100 mg/m²)联合阿霉素(60~80 mg/m²)化疗方案, 随机分为试验组(盐酸帕洛诺司琼组)和对照组(盐酸昂丹司琼组), 每组各40例。比较两组预防化疗急性期的呕吐总有效率、延迟期的呕吐完全缓解率以及用药后不同时间恶心的完全控制率, 同时对不良反应进行评价。  结果  试验组对于预防急性期呕吐的总有效率为80%, 与对照组77.5%比较差异无统计学意义(P=0.785)。延迟期(分别观察化疗后第3天、第5天和第7天)的呕吐完全缓解率, 试验组均高于对照组(P < 0.05)。用药后第5天和第7天试验组恶心的完全控制率明显高于对照组, 差异有统计学意义(P=0.039, P=0.034)。两组不良反应比较差异无统计学意义(P > 0.05)。  结论  盐酸帕洛诺司琼注射液能更好的预防骨肉瘤大剂量化疗引起的延迟性恶心和呕吐, 对青少年患者使用有较好的安全性。     

A randomized study of very accelerated radiotherapy with and without amifostine in head and neck squamous cell carcinoma

Purpose: The aim of this study was to assess whether amifostine could minimize acute mucositis induced by a very accelerated irradiation regimen in patients with advanced head and neck squamous cell carcinoma (HNSCC).

Methods and Materials: Between May 1996 and February 1998, 26 patients with an inoperable nonmetastatic Stage IV HNSCC were entered in this study. The treatment consisted of very accelerated radiotherapy given 64 Gy in 3.5 weeks. The patients were randomized to receive or not 150 mg/m², amifostine (Ethyol, U.S. Bioscience) 15–30 min prior to each radiation session.

Results: Of the 13 patients who received amifostine, definitive interruption of amifostine occurred in 5 cases (38%), due to tolerance problems (vomiting, liver enzyme elevation, generalized erythema). The distribution of Grade 4 mucositis (WHO) was 1 case versus 8 cases, with and without amifostine, respectively. The mean duration of “at least Grade 3” mucositis (WHO) was 25.1 days versus 49.2 days with and without amifostine (p = 0.03). In the amifostine group, 11/13 of the patients required a feeding tube (nasogastric tube or medical gastrostomy), because of acute mucositis, whereas in the control group a feeding tube was necessary in all cases. The mean duration of the use of this feeding tube was 1 month versus 2.5 months with and without amifostine respectively (p < 0.01). Local-regional control was not different between both arms with a median follow-up of 15 months.

Conclusion: Despite the limited number of patients, this pilot randomized study suggests that amifostine was able to markedly reduce the severity and duration of mucositis induced by very accelerated radiotherapy. However, the tolerance of this twice daily amifostine schedule was relatively poor.     

Different cutoff values of Cyfra 21-1 for cavitary and noncavitary lung cancers

Study objectives: Cell lysis and tumor necrosis release cytokeratin, a tumor marker of lung cancer, into the serum. The serum cytokeratin level can also be elevated in benign cavitary lung diseases. The purpose of this study was to evaluate whether Cyfra 21-1 can differentiate malignant lung diseases from benign diseases with cavitary lesions. Design: This study is a retrospective review of the case records of patients with lung lesions seen during a 4-year period from January 1993 to May 1996. Setting and patients: Serum Cyfra 21-1 levels were measured in 306 patients with lung cancer (n=143) or benign lung disease (n=163). The patients were grouped according to radiologic evidence of cavitary lung lesions. Lung cancer included both non-small cell (n=123) and small cell (n=20) lung cancers, and the benign diseases include tuberculosis (n=87), abscess (n=26), pneumonia (n=4), and others (n=46). Measurements and results: Although Cyfra 21-1 clearly differentiated cavitary lung cancer (15.0, 9.1–29.8 ng/ml, median and interquartile range, n=39) from benign cavitary disease (P<0.001), and noncavitary lung cancer from benign noncavitary disease (1.7, 0.9–2.6 ng/ml, n=108, P<0.001), it could not differentiate noncavitary lung cancer (5.0, 2.1–12.4 ng/ml, n=104) from benign cavitary diseases (3.3, 1.4–8.3 ng/ml, n=55, P=0.45). Conclusions: Serum Cyfra 21-1 is a useful tumor marker for differentiating benign from malignant lung diseases. However, different cutoff values are needed, depending on the presence of cavitary lesions. We recommend cutoff values of 30 ng/ml for cavitary lung diseases and 6 ng/ml for noncavitary lung diseases. If there are no radiologic data, a cutoff value of 15 ng/ml is recommended.     

Effects of different combinations of comprehensive treatment on survival of patients with locally advanced head and neck squamous cell carcinoma:post-hoc analysis of a phase Ⅲ randomized controlled clinical trial

Objective To compare the effects of comprehensive treatment with different combinations of radiotherapy, chemotherapy and surgery on the survival of patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC). Methods From September 2002 to May 2012, 222 patients were enrolled in a randomized controlled clinical trial to compare the clinical efficacy between preoperative radiotherapy and preoperative concurrent chemoradiotherapy. The chemotherapy was performed at the beginning of the radiotherapy, with cisplatin 30 mg/m² every week. Conventional radiotherapy or intensity-modulated radiotherapy (IMRT) was adopted. Clinical efficacy was evaluated during radiotherapy to 50Gy in all patients. Whether surgery or original treatment regime was given was determined according to the clinical efficacy. The survival of different therapeutic methods was analyzed by Kaplan-Meier method. ResultsThe median follow-up time was 59 months (7-139 months). All patients were divided into four groups:radiotherapy group (R group,n=84), concurrent chemo-radiotherapy group (R+C group, n=67), preoperative radiotherapy group (R+S group, n=34) and preoperative concurrent chemoradiotherapy group (R+C+S group, n=37). The 5-year overall survival rates were 32%, 44%, 51%, and 52%, respectively (R+C+S group vs. R group, P=0.047). The 5-year progression-free survival rates were 34%, 48%, 49%, and 61%, respectively (R+C Group vs. R group, P=0.081;R+C+S group vs. R group, P=0.035). The 5-yeal distant metastasis-free survival rates were 70%, 85%, 65%, and 73%, respectively (R+C group vs. R+S group, P=0.064;R+C group vs. R+S group, P=0.016). Conclusions Compared with radiotherapy alone, comprehensive treatment with different combinations can improve the long-term survival of LA-HNSCC patients. Radiotherapy combined with chemotherapy has a tendency to improve the distant metastasis-free survival rate, The optimal comprehensive treatment modality that improves the overall survival of LA-HNSCC patients remains to be explored.     

A cross sectional quality of life study of 116 recurrence free head and neck cancer patients. The first use of EORTC H&N35 in Danish

The quality of life questionnaire EORTC C30 with the head and neck specific module H&N35 has been validated in many languages and cultural settings, but the H&N35 module has not been formally translated to and validated in Danish. This validation was the purpose of the current study. In a cross sectional study 116 of 120 (97%) recurrence free head and neck cancer patients returned a valid questionnaire. The patients were attending follow up after radical radiotherapy (n=83), surgery (n=33) for cancer of the larynx (n=44), pharynx (n=34) or oral cavity (n=38). The previously described psychometric properties of the questionnaire were confirmed with the Danish translation. Nevertheless, there were some foreseeable problems with heavily skewed endpoints. Several scales of the questionnaire were sensitive to patient, tumour and treatment related factors: Good performance, high age, male gender, laryngeal cancer, low tumour stage and surgery correlated with a low score on the symptom scales or high score on the function scales. Symptom intensity increased with time since therapy in patients who had surgery and decreased in the irradiated patients. In conclusion, the current validation study confirmed the psychometric properties of the EORTC H&N35 questionnaire. The questionnaire detected correlations between clinical factors (performance status, gender, age, stage, site, time since therapy, treatment) and a large number of QoL factors. EORTC H&N35 in conjunction with EORTC C30 is a valid and informative tool in assessing quality of life, also in Danish head and neck cancer patients.     

放疗延迟对乳腺癌不同分子亚型患者预后的影响

目的 探讨放疗延迟对乳腺癌不同分子亚型患者预后的影响。方法 收集2007年1月—2012年12月在我院行乳腺癌根治术患者341例,其中Luminal A型149例(对照组83例,放疗延迟组66例),Luminal B型105例(对照组63例,放疗延迟组42例),HER2+型43例(对照组28例,放疗延迟组15例),三阴型患者44例(对照组27例,放疗延迟组17例)分析放疗延迟组与对照组预后是否存在差异。结果 Luminal A型、Luminal B型、HER2+型、三阴性型在对照组和放疗延迟组的局部复发率分别为(4.8% vs. 9.1%,P=0.301),(4.7% vs. 19.0%,P=0.019),(7.1% vs. 33.3%,P=0.027),(11.1% vs. 35.3%,P=0.053);远处转移率分别为(9.6% vs. 10.6%,P=0.845),(11.1% vs. 14.2%.P=0.234),(32.1% vs. 40.0%,P=0.937),(37.0% vs. 41.2%,P=0.784);无瘤生存率分别为(85.5% vs. 80.3%,P=0.395),(84.1% vs. 66.7%,P=0.037),(60.7% vs. 33.3%,P=0.087),(55.5% vs. 23.5%,P=0.037);总生存率分别为(94.0% vs. 90.9%,P=0.539),(84.1% vs. 80.9%,P=0.672),(67.9% vs. 60.0%,P=0.606),(59.2% vs. 41.2%,P=0.242)。Cox回归分析结果显示肿瘤大小(HR=3.156,P=0.043)、淋巴结转移(HR=1.074,P=0.001)、TNM(HR=8.591,P=0.009)和分子亚型(HR=2.092,P＜0.001)为乳腺癌患者预后的独立影响因素。结论 Luminal B型及HER2+型患者的局部复发率均因放疗延迟而明显增高,Luminal B型及三阴型的无瘤生存率因放疗延迟而明显降低。肿瘤大小、淋巴结转移、TNM分期和分子亚型是影响患者总生存期的独立危险因素。     

Thallium-201 scintigraphy is not predictive of late cardiac complications in patients with Hodgkin's disease treated with mediastinal radiation

Purpose: To assess whether abnormalities depicted by Thallium-201 scintigraphy can predict the occurrence of late cardiac complications in patients with Hodgkin’s disease treated with mantle field radiation therapy.

Methods and Materials: Thallium scintigraphy was performed in 49 patients at a median of 75 months after initial treatment (range 28–208 months). Initial treatment consisted in chemotherapy, given to two-thirds of the patients and mantle field radiation, delivered to all patients, using a 25-MV linear accelerator. Myocardial perfusion defects were observed in 78% of patients on thallium scintigraphy. These patients had their cardiac status reassessed at a median follow-up of 13.5 years after treatment.

Results: Forty-two patients were assessable, as data on the cardiac status were missing in 7 patients. The majority of patients received at least 40 Gy, and 75% of them were treated with one field per day. The median follow-up of patients is 13.5 years (range 9–24.5). Eleven cardiac complications were observed in 9 patients (coronary artery disease [n = 2], conduction-system abnormalities [n = 3], valvular defects [n = 5], and congestive heart disease [n = 1]). The median 15-year actuarial incidence of cardiac complications was 21% (95% confidence interval of 9–40%). The positive and negative predictive value of thallium scintigraphy was 19% and 77%, respectively. The univariate analysis showed that the extent of left ventricle exposure to irradiation was an adverse prognostic factor, and chemotherapy administered before mantle field irradiation was of borderline significance.

Conclusion: Thallium scintigraphy is not predictive of late cardiac complications. The extent of left ventricle exposure to radiation and possibly chemotherapy given before radiation treatment are adverse prognostic factors.     

Radiotherapy after high-dose chemotherapy and peripheral blood stem cell support in high-risk breast cancer

To assess the toxicity and efficacy of radiotherapy with respect to locoregional control after adjuvant high-dose chemotherapy for patients with breast cancer. At first, radiotherapy was withheld because of toxicity concerns, but it was introduced in 1995 because of reported high locoregional relapse rates.

Between 1992 and 1998, 40 patients with Stage II–III high-risk breast cancer received adjuvant high-dose chemotherapy consisting of thiotepa, mitoxantrone, and cyclophosphamide and peripheral blood stem cell support after four cycles of induction chemotherapy. The chest wall or breast, as well as the supraclavicular nodes, were irradiated with electrons and photons to a median dose of 50.4 Gy in 20 patients. Six additional patients received only supraclavicular irradiation to a median dose of 50.4 Gy. Acute toxicity was scored clinically. Pulmonary function tests were performed in 14 irradiated patients before high-dose chemotherapy and 1.1–4.4 years (median 1.6) after irradiation. The median follow-up time of living patients was 33 vs. 67 months in irradiated (n = 26) and nonirradiated (n = 14) patients, respectively.

G2 and G3 hematologic toxicity occurred in 1 patient each. No clinical pneumonitis or clinical impairment of lung function was observed. After 1–2 years, the lung function tests showed only minor changes in 4 patients. The 3-year locoregional control rate was 92% in the irradiated patients vs. 58% in the nonirradiated patients (p = 0.049, actuarial analysis).

In this series, adjuvant radiotherapy after adjuvant chemotherapy for breast cancer appeared well tolerated, with improved local regional control and without significant side effects. Longer follow-up and more patient accrual, as well as Phase III trials, are necessary for confirmation.     

Economic analysis of amifostine as adjunctive support for patients with advanced head and neck cancer: preliminary results from a randomized phase II clinical trial from Germany

In a randomized phase II trial in Germany, we investigated the clinical and economic impact of amifostine protection against the hematological and oral toxicities of carboplatin administered concurrently with standard fractions of radiotherapy. 28 patients with squamous cell carcinomas of the head and neck received adjunctive or primary radiotherapy (5 days per week with daily fractions of 2 Gy, up to a total dose of 60 Gy) in conjunction with carboplatin (70 mg/m2) on days 1-5 and days 21-26. All patients received radiation encompassing at least 75% of the major salivary glands. Patients were randomized to receive radiation and carboplatin (RCT) alone or RCT preceded by rapid infusion of amifostine (500 mg) on days carboplatin was administered. The 14 patients who received amifostine, in comparison to 14 patients in the control arm, had significantly fewer episodes of grade 3 or 4 thrombocytopenia (p = 0.001), mucositis (p = 0.001), and xerostomia (p = 0.001). The patients receiving amifostine accrued significantly lower supportive care costs for resources related to infection ($241 vs. $1,275, p < 0.01), red blood cell and platelet support ($286 vs. $1,276 p = 0.06) alimentation ($343 vs. $894, p = .01), and hospitalization ($286 vs. $2,429, p < 0.01). Overall, including the costs of amifostine, mean per patient supportive care costs were $4,401 for the amifostine group and $5,873 (p = .02) for the control group. Our results from a randomized phase II trial indicate that selective cytoprotection with amifostine potentially offers clinical and economic benefits in patients with advanced head and neck cancer receiving radiochemotherapy. Additional economic studies alongside randomized phase III trials and from other countries are needed.     

Selective cytoprotection with amifostine in concurrent radiochemotherapy for head and neck cancer

Background: Amifostine has reduced toxicities associated with radiationtherapy and platinum-based chemotherapy. In a phase II randomized trial, weinvestigated the ability of amifostine to reduce the toxicity of carboplatinplus radiotherapy (RCT) in patients with head and neck cancer.Patients and methods: Thirty-nine patients with stage III or IV squamouscell carcinomas of the head and neck received RCT (following surgery or asprimary treatment). Radiotherapy was given five days per week with dailyfractions of 2 Gy, up to a total dose of 60 Gy in conjunction withcarboplatin 70 mg/m² on days 1 through 5 and days 21 through26. Eligible patients were randomised to receive RCT alone or preceded by arapid infusion of amifostine (500 mg) on the days when carboplatin wasadministered.Results: Patients receiving amifostine + RCT (n = 25) had significantlyreduced mucositis (P = 0.0001) and xerostomia (P = 0.0001) in comparisonwith patients receiving RCT alone (n = 14). Additionally, patients receivingamifostine + RCT had significantly less thrombocytopenia (P = 0.001) andleukopenia (P = 0.001). At 12 months following therapy, 79% ofpatients receiving amifostine + RCT had no evidence of disease compared with64% of those receiving RCT alone.Conclusions: Amifostine reduces the RCT-induced toxicities in patients withhead and neck cancer and has no negative impact on antitumour efficacy.     

The Effect of Sequential Methotrexate and 5-Fluorouracil in Patients with Recurrent Head and Neck Cancer

Sequential methotrexate and 5-fluorouracil was given to 105 patients with recurrent head and neck cancer. All 105 patients had previously received radiotherapy in curative doses; 41 patients had also been surgically treated and 21 had received previous chemotherapy for recurrence. The treatment consisted of methotrexate 125 mg/m², followed by 5-fluorouracil 600 mg/m² after 1 h. Leucovorin rescue was administered after 24 h. A response was observed in 24 patients (23%), including 9 (9%) with complete response. The majority of the responders were patients with a good performance status and with primary tumour in the oropharynx. The toxicity was not negligible, as 5 patients (5%) died of treatment-related causes, mainly due to leukopenia, which was the most frequent and important complication. This sequential methotrexate/5-fluorouracil treatment-schedule cannot be recommended for recurrent head and neck cancer patients.