The treatment of early squamous cell carcinoma of the piriform fossa

The treatment of early piriform fossa cancer can be either primary radiotherapy with salvage surgery, if necessary, or with primary surgery. The present study investigates 65 patients with T₁, ≥₂ or T₃ stage disease with no cervical lymph node metastases at presentation. Of this group, 17 were treated by primary irradiation, 34 underwent primary surgery and 14 were unsuitable for any curative treatment. The adjusted actuarial 5-year survival rate for those patients receiving primary radiotherapy was 55% (95% CI 16–78%) and for the surgery group it was 44% (95% CI 18–67%). This difference was not significant (χ²₁= 1.29). The median survival for untreated patients was 7 months (4–12 months). There was no significant differences in the time to recurrence at the primary site or in the neck, or in survival after recurrence at these sites. Thirty-five per cent of patients treated by primary irradiation were controlled at the primary site compared with 68% in the surgical group. Failure in the neck was similar for the two groups at 12% and 15% respectively. Salvage surgery was effective for the radiotherapy group with eight out of 11 patients being suitable for treatment. In the final analysis in the radiotherapy group two patients were alive and with their larynx and two alive without their larynx, the remainder of patients having died from the original tumour, intercurrent disease or second primary tumours. The survival figures for the surgery group were proportionately similar except of course, that all patients had lost their larynx. Radiotherapy with salvage surgery for recurrence is a safe oncological treatment option. A high failure rate at the primary site is disappointing but if placed in perspective still allows half the survivors to retain their larynx.     

Polyadenylic–Polyuridylic Acid Plus Locoregional Radiotherapy Versus Chemotherapy with CMF in Operable Breast Cancer: a 14 Year Follow-up Analysis of a Randomized Trial of the Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC)

With a median follow-up of 14 years, the combination of polyadenylic–polyuridylic acid plus locoregional radiotherapy (257 patients) has significantly improved disease-free survival (p=0.03) and significantly reduced the incidence of metastases (p=0.04) when compared to CMF alone (260 patients), in women with operable breast cancer. The trial does not, however, permit an appreciation of the respective role of radiotherapy and PolyAU in these results.     

Increased risk of second cancers following breast cancer: Role of the initial treatment

Objectives and methods.The risk of second primary malignancies (SMN) was studied in a cohort of 4,416 one-year survivors of a breast cancer. The role of the menopausal status and of the initial treatment modalities (surgery, radiotherapy, and chemotherapy) was investigated. Results.Excluding second primary breast cancer and non-melanoma skin cancer, a total of 193 (4.4%) patients developed a SMN between 1973 and 1992, compared with 136 expected (Standardised Incidence Ratio, SIR=1.4, 95% CI (1.2–1.6)). No trend towards either an increase or a decrease was noted in the SIR with time after treatment (p=0.2). The greatest increase in the relative risk concerned soft tissue cancers (SIR=13.0, 95% CI: 6.8–22.3), followed by leukaemia (SIR=3.1, 95% CI: 1.7–5.0), melanoma (SIR = 2.7, 95% CI: 1.4–4.8), kidney (SIR=2.5, 95% CI: 1.2–4.5), ovary (SIR=2.0, 95% CI: 1.2–3.1) and uterine tumours (SIR=1.9, 95% CI: 1.4–2.5). The SIR was 3.0 (95% CI 1.8–4.7) in women under 40 at the time of the breast cancer, 1.9 (95% CI : 1.4 – 2.4) in those aged 40–49 and 1.2 (95% CI 1.0–1.4) in those aged 50 or more. In the 2,514 women who had received radiotherapy as initial treatment without chemotherapy, the SIR for all SMN was 1.6 (95% CI: 1.1–2.3) fold higher than in those who had not received radiotherapy as initial treatment. Conclusion.In conclusion, this study confirms the increased risk of second malignancies in women treated for a breast cancer, and particularly in those who were younger at the time of treatment for breast cancer. Our results also suggest that radiotherapy may play a role in the onset of these second lesions.     

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.     

Possibilities of preventing osteoradionecrosis during complex therapy of Tumors of the oral cavity

In recent years, there has been a dramatic increase in the number of tumors of the head and neck. Their successful treatment is one of the greatest challenges for physicians dealing with oncotherapy. An organic part of the complex therapy is preoperative or postoperative irradiation. Application of this is accompanied by a lower risk of recurrences, and by a higher proportion of cured patients. Unfortunately, irradiation also has a disadvantage: the development of osteoradionecrosis, a special form of osteomyelitis, in some patients (mainly in those cases where irradiation occurs after bone resection or after partial removal of the periosteum). Once the clinical picture of this irradiation complication has developed, its treatment is very difficult. A significant result or complete freedom from complaints can be attained only rarely. Attention must therefore be focussed primarily on prevention, and the oral surgeon, the oncoradiologist and the patient too can all do much to help prevent the occurrence of osteoradionecrosis. Through coupling of an up-to-date, functional surgical attitude with knowledge relating to modern radiology and radiation physics, the way may be opened to forestall this complication that is so difficult to cure.     

Phase I/II dose escalation study of docetaxel and carboplatin combination supported with amifostine and GM-CSF in patients with incomplete response following docetaxel chemo-radiotherapy: additional chemotherapy enhances regression of residual cancer

Taxanes have been shown to interact with anti-apoptotic proteins. In the present study we investigated whether the addition of taxane in combination with DNA damaging drugs can further enhance tumor shrinkage in cases with incomplete response to radiotherapy. Since the dose of docetaxel in combination with carboplatin is not known, the above hypothesis was tested in the context of a dose escalation phase I study. Twenty-eight patients with locally advanced chest or pelvic tumors, showing residual disease on CT scans performed 40 d following docetaxel radio-chemotherapy, were recruited in a dose escalation protocol of docetaxel/carboplatin supported with amifostine and GM-CSF. The starting dose of docetaxel was 40 mg/m² every 2 weeks. Carboplatin dose was calculated using the Calvert formula and was escalated in cohorts of 4 patients (starting dose AUC2 every two weeks; AUC0.5 increments up to AUC3). Thereafter the docetaxel dose was increased to 50 and 60 mg/m², while carboplatin was escalated (by AUC0.5 increments) starting from AUC3 and AUC4 respectively. Amifostine (600 mg/m²) was administered i.v. before carboplatin and GM-CSF (480μg) was injected s.c. on days 5, 6 and 10, 11 of each cycle. Six cycles were given and response was assessed 2 weeks after the end of chemotherapy. None out of four patients treated in the 6th dose level cohort (50mg/m² of docetaxel and AUC4 of carboplatin every 2 weeks) showed any grade 2–4 hematologic toxicity. Mild non-hematologic toxicity such as neuropathy, leg edema, pleural effusion, pyrexia, alopecia grade 2 and hypersensitivity was observed in 4–12% of patients. Out of four patients treated in a 7th cohort (docetaxel 60mg/m² and carboplatin AUC4), one developed grade IV neutropenia and two developed grade 3 severe asthenia requiring treatment delay for 2 weeks. Out of 11 patients with PR following docetaxel radio-chemotherapy, 7 (63%) showed CR after docetaxel/carboplatin additional chemotherapy. Eight out of 17 patients with MR following docetaxel radio-chemotherapy showed PR (47%) and one showed CR (6%) after additional chemotherapy. High dose combined docetaxel (50 mg/m²) and carboplatin (AUC4) chemotherapy can be safely administered on a two-weekly basis if supported with amifostine and GM-CSF. Such an additional therapy may be important in patients with incomplete response after chemo-RT. Broad spectrum cytoprotection with amifostine and GM-CSF may also contribute to the reduction of incidence of neurosensory reactions and asthenia in patients treated with taxanes.     

Expression of Egr-1 gene and its correlation with the oncogene proteins in non-irradiated and irradiated esophageal squamous cell carcinoma

We study the expression of early growth response gene-1 (Egr-1 gene) in non-irradiated and irradiated human esophageal cancer tissues, and its relationship with the expression of C-fos, C-jun onco-proteins as well as Egr-1 target gene proteins P53, Rb and Bax expression. In situ hybridization (ISH) and immunohistochemistry (IHC) were used respectively to detect Egr-1 mRNA, Egr-1, C-fos, C-jun, P53, Rb and Bax proteins in 80 surgically resected non-irradiated and irradiated tumor specimens of esophageal squamous cell carcinoma. Egr-1 gene mRNA and Bax protein were located in the cytoplasm, whereas Egr-1, C-fos, C-jun, P53, Rb proteins were located in the nuclei. Egr-1 was expressed in nine out of 40 cases (22.5%) of non-irradiated and 23 of 40 cases (57.5%) of irradiated tumor specimens. No correlation was found between Egr-1 gene expression and C-fos, C-jun onco-proteins expression, neither was any correlation disclosed between Egr-1 gene expression with its target gene protein expression. Patients who underwent radiotherapy with Egr-1 overexpressed in their cancer tissue had better prognosis. Radiotherapy up-regulates Egr-1 expression in esophageal carcinoma. Egr-1 overexpression may be a potential radiation response gene marker and may play an important role in prognosis of esophageal squamous cell carcinoma.     

原发性肝癌切除术前应用立体定向适形放疗的价值

目的　探讨立体定向适形放疗对原发性肝癌的治疗效果及其术前应用的价值。方法　 1 998年 5月至 2 0 0 1年 1 0月 ,2 5例肝癌行术前短程大剂量立体定向适形放疗 2周后手术切除 ,与同期单纯手术切除的病例对照 ,进行病理、肝功能、血常规、AFP、术中出血量、术后复发率及生存率的分析研究。结果　立体定向适形放疗能有效杀灭肿瘤细胞 ,导致癌周小血管、淋巴管闭塞及纤维机化带形成 ,显著缩小肿瘤体积 (P<0 .0 1 ) ,减少术中出血量 (P<0 .0 5 ) ,提高术后近期 AFP转阴率 (P<0 .0 1 ) ,降低术后 1年复发率 (P<0 .0 1 ) ,提高术后 2年生存率 (P<0 .0 1 )。同时 ,没有严重副作用。　结论　立体定向适形放疗是治疗肝癌的有效手段 ,术前短程大剂量冲击放疗可以提高手术切除率 ,改善预后 ,增加二期切除的机会     

三维适形放射治疗对局部中晚期胰腺癌的临床意义

目的:用6 MV光子线的三维适形放射治疗计划与常规放疗计划进行比较,并治疗局部中晚期胰腺癌,观察近期疗效.方法:10例确诊为局部中晚期胰腺癌患者,在三维治疗计划系统上,分别制定三维适形治疗计划和常规三野、四野治疗计划.比较靶区体积、等剂量线包括的组织体积及重要器官所受的照射剂量.结果:对于吸收40%～50%之间的照射剂量区,三维适形治疗所接受的照射体积明显小于常规三野、四野治疗(P＜0.01).脊髓和左肾所受的平均放射剂量以三维适形治疗计划的剂量最低.结论:对于中晚期胰腺癌,三维适形放射治疗较常放疗设计在剂量体积上有明显的改善,提供了使病人完成全程放疗的适宜方法.     

Inflammatory breast cancer: enhanced local control with hyperfractionated radiotherapy and incisional vincristine, ifosfamide and epirubicin

Local control rate for inflammatory breast cancer (IBC) is <50% with standard chemotherapy-radiotherapy regimen. Nineteen women (age range 40–65, median 50 years) with IBC (18 patients) or with a primary tumour of >10 cm (one patient) received a novel treatment comprising hyperfractionated radiotherapy (HFRT) sandwiched between two cycles of infusional chemotherapy using vincristine, ifosfamide and epirubicin (VIE). The primary endpoint was local control.
VIE was continuously infused for six weeks via a Hickman's line using a Deltec CADD-1 ambulatory pump. Ifosfamide (3 gm/m²) mixed with equi-dose mesna was infused for seven days and alternated every week with an infusion of epirubicin (50 mg/m²) mixed with vincristine (1.5 mg/m²). HFRT consisted of 1.5 Gy twice daily for 34 fret (51 Gy) followed by a boost of 15 Gy in 10 fret. The total treatment time was less than 22 weeks.
Median follow-up was 37 months. Local control rate was 58%. Three patients failed to respond initially and five relapsed in the breast at a median time of 36.8 months. Median overall and disease-free survival was 18 and 25.3 months respectively. Toxicity from VIE was minimal (WHO gd 3 emesis - two patients, gd 3 mucositis - one patient, neutropenic sepsis - three patients). Radiotherapy caused moist desquamation in 17/19 patients. Twenty-four central lines were complicated by seven line infections, three thromboses, and one extravasation.
The local control rate of 58% with VIE+HFRT appears similar to reported chemoradiotherapy regimen, although the treatment time of 22 weeks is much shorter than other regimens which take up to 12 months. Toxicity is acceptable. Hickman-related complications need to be reduced. The study is ongoing.