Colloid cancers of the breast. Value of radiotherapy. A series of 138 cases treated at the Curie Institute

A series of 138 mucinous breast carcinomas was treated at the Institut Curie from 1970 to 1980: 107 were diagnosed as "pure" mucinous carcinoma and 31 as "mixed" mucinous carcinomas. Fifty per cent of the cases were stage T2 and 78% N0-N1a. Treatment methods were radical mastectomy in 113 cases (82%) with pre-operative irradiation for 37 patients and post-operative irradiation for 14 patients. A conservative treatment was used for 25 patients, consisting either of lumpectomy followed by radiotherapy (in 15 cases) or radiotherapy alone (in 10 cases). The five-year actuarial survival rate was 81% for the "pure" group and 87% for the "mixed" group; it was 70 and 75%, respectively, at ten years follow-up. In this series, survival was not influenced by the type of treatment. The efficacy of radiotherapy was evaluated from the local recurrence rate: only four local failures among the 25 conservative treatments were noted. Our conclusion is that radiotherapy, with or without lumpectomy, is efficient in mucinous breast carcinoma and could be useful in selected cases.     

Reirradiation of head and neck cancers. Presentation of 35 cases treated at the Gustave Roussy Institute

Thirty-five patients with head and neck carcinoma who were treated with a second course of radiotherapy for relapse or second malignancy at the Gustave Roussy Institute between 1973 and 1981 were studied. Immediate tolerance for total doses greater than 80 Gy was good but 37% of patients suffered from delayed necrosis or bleeding. Thirty-seven per cent of lesions were locally controlled at 3 months and 97% of patients showed a subjective improvement to reirradiation. Local control was obtained in 53% of patients aged between 40 and 60 as compared to 19% in other age groups, and was obtained in 55% of patients who were irradiated a second time with a dose greater than 60 Gy as compared to 8% for doses less than 60 Gy. Complications following treatment are related to failure to achieve local control and area of second treatment fields greater than 70 cm2. Survival was worse for those patients having an interval less than 12 months between the two courses of irradiation and those in whom local control was not achieved.     

A pilot study of intraarterial chemotherapy with cisplatin in locally advanced head and neck cancers

A prospective pilot study involving preoperative intraarterial chemotherapy with cisplatin in locally advanced oral and oropharyngeal carcinomas was initiated in March 1982. Twenty patients with TNM Stages III and IV disease underwent continuous intraarterial chemotherapy with cisplatin (90 mg/m2, at 1 mg/hour) and intravenous chemotherapy with methotrexate (50 mg/m2 X 1 dose). Arterial access was obtained by retrograde cannulation of the superficial temporal artery. One patient died of sepsis from leukopenia (mortality 5%). Catheter-related complications, most of them avoidable, totalled 30%. The total tumor response rate was 94%. With a median duration of follow-up of 14 months, the median survival of the group was not yet reached at 39 months. Eleven patients subsequently underwent definitive surgery and radiation with curative intent. When compared with matched historical controls, survival benefit was demonstrated: 60% versus 28% alive at 39 months (P = 0.015). Regional chemotherapy of cancers of the head and neck region is a feasible procedure with acceptable and avoidable morbidity. It should continue to be investigated in experimental protocols to improve patient survival.     

Chemoradiotherapy as preoperative treatment in locally advanced unresectable pancreatic cancer patients: results of a feasibility study.

PURPOSE: The combination of radiotherapy and fluorouracil (5-FU) in patients with locally unresectable pancreatic carcinoma has led to a significant increase in survival in comparison with radiotherapy alone. Doxifluridine (5-DFUR) is an orally active fluoropyrimidine, and its cytotoxic metabolite (5-FU) may concentrate in areas of high tumor vascularization. This trial was carried out with the aims of improving locoregional control and making lesions resectable in patients with unresectable pancreatic cancer. METHODS: 5-DFUR was given at a dose of 500 mg/m2 b.i.d. by way of mouth for 4 days every other week for a total of four courses, with leucovorin 25 mg b.i.d. orally being given 2 hours before each 5-DFUR administration. External beam RT was administered at a dose of 1000 cGy per week for 3 weeks, followed by a 2-week break and then by 1000 cGy per week for a further 2 weeks (a total dose of 5000 cGy). The patients were restaged 4 weeks after the end of treatment and explored for resection in cases of partial response (PR). RESULTS: A total of 32 patients were treated between 1992 and 1997. Ab initio unresectability was shown by laparotomy (16 cases) or computed tomography (16 cases), and was due to vascular invasion in 27 patients, massive regional nodal metastases in nine, and both in four. The median age was 63 years (range 36-71); performance status (PS) (ECOG): 0-1 = 28 and PS 2 = 4. All the patients had measurable disease and were evaluable for response. There were seven PR (22%), 10 SD (31%), and 15 PD (47%). All of the responders underwent surgical exploration, and radical resection was possible in 5. Three of these patients are still disease-free with a follow-up of 18, 27, and 65 months; the other two cases relapsed 11 and 14 months after surgery. The median survival time was 9 months for the entire group, and 1-year survival rate was 31%. The treatment was never stopped because of toxicity. There were no CTC-NCI grade 3 or 4 toxic events; grade 1-2 diarrhea was observed in 10 cases. CONCLUSIONS: This preoperative regimen was feasible and led to a successful surgical resection in 16% of otherwise inoperable cases. The median survival was comparable with the results obtained after 5-FU infusion plus radiotherapy. The resectability rate, and the benefit in terms of survival in the resected patients, make these results worthy of confirmation by larger studies.     

Treatment of epitheliomas of the parotid. Apropos of 93 cases treated at the Curie Institute

From 1955 through 1982, a series of 93 cases of parotid gland carcinoma were treated at the Institut Curie: 55 primarily and 28 for recurrent tumors. Treatment modalities included surgery alone (n : 14), surgery followed by radiotherapy (n : 43), and radiotherapy alone (n : 36). The most advanced cases were mostly in the latter group. With a mean follow-up of 13 years, the actuarial loco-regional control is 67% (62/93) and the median survival 10 years. Ultimate loco-regional control was achieved in 86% of cases managed by surgery alone, 88% of cases managed by surgery and radiotherapy and 33% of cases managed by radiotherapy. In the latter group, control rate was 42% (8/19) in those primarily treated by radiotherapy. Prognosis was related to histology. Twenty patients (22%) presented distant metastasis. The potential advantages of neutron irradiation for parotid neoplasms is discussed.     

放疗在头颈部晚期肿瘤器官功能保全治疗中的作用

器官功能保全治疗在头颈部肿瘤病人的治疗中有非常重要的地位.目前头颈部晚期肿瘤的非手术治疗方法主要有放射治疗和化疗联合放射治疗.超分割治疗和加速超分割治疗与常规放射治疗比较,能够提高局部控制率和器官功能保全率.诱导化疗加放疗能够使约60%的喉癌患者保留喉功能,与常规放射治疗比较,不能提高生存率.同步放化疗显著提高器官功能保全率,是目前器官功能保全性非手术治疗的主要治疗方案,同步放化疗与非常规分割方式结合能否经一步提高器官功能保全率仍需要进一步研究.一些新的方法如新药及不同给药方式,调强放射治疗,分子靶向治疗,乏氧增敏剂等在头颈肿瘤治疗中的作用的试验正在进行中.     

End points for new agents in induction chemotherapy for locally advanced head and neck cancers.

More than 60% of patients diagnosed with squamous cell carcinoma of the head and neck present at a locally advanced stage. Although multimodality therapy has improved locoregional control, the 5-year survival rate of this population rarely exceeds 30%. In this review, we analyzed the impact of chemotherapy in the management of locally advanced head and neck cancer and we underline the potential benefit of induction chemotherapy. The Meta-Analysis of Chemotherapy in Head and Neck Cancer collaborative group has suggested a survival advantage of 5% at 5 years for platin-5-fluorouracil induction chemotherapy. We have analyzed cofactors that may affect the survival of head and neck patients and propose new end points for assessment of the efficacy of induction chemotherapy. The detrimental effect of second primary tumors on long-term results is stressed and we have suggested the use of overall 2-year survival as a surrogate end point for induction chemotherapy efficacy. Finally, we have examined the impact of new cytotoxic agents and present the promising results of new taxane-based combinations.     

Carbonic anhydrase IX expression and tumor oxygenation status do not correlate at the microregional level in locally advanced cancers of the uterine cervix.

PURPOSE: Carbonic anhydrase IX (CA IX) can be induced by hypoxia in vitro and shows an immunohistochemical expression pattern that is predominantly found in perinecrotic tumor areas and correlates with exogenous markers of hypoxia, such as pimonidazole. CA IX might therefore serve as an endogenous marker of tumor hypoxia, although comparisons of CA IX immunostaining with direct oxygenation measurements using pO2 microsensors have thus far yielded contradictory results. EXPERIMENTAL DESIGN: Because tumor heterogeneity may be among the factors responsible for the discrepancy between the two methods, CA IX expression in tissue samples originating from oxygen microelectrode tracks of locally advanced cervical cancers was assessed in this study. Seventy-seven biopsy specimens were analyzed immunohistochemically using an anti-CA IX rabbit polyclonal antibody and semiquantitative scoring. RESULTS: CA IX expression showed no correlation with the oxygenation variables median pO2 and hypoxic fraction 2.5, 5, or 10. Cases with higher International Federation of Gynecology and Obstetrics stages (IIb-IVa) exhibited stronger expression of CA IX (P = 0.035) and CA IX expression tended to be more prevalent in node-positive patients (P = 0.051). CONCLUSIONS: These data indicate that CA IX cannot be recommended as a substitute for oxygen microelectrode measurements. That the expression of CA IX does not correlate with the oxygenation status may be due to the degree to which other factors, such as nutrient (e.g., glucose) deficiency or the action of oncogenic mutations, can modulate the in vivo expression of this protein, rendering a strict association with tumor hypoxia too unreliable for clinical use.     

Compliance and outcomes in locally advanced head and neck cancer patients treated with alternating chemo-radiotherapy in clinical practice

BACKGROUND AND AIMS: To evaluate the feasibility in clinical practice of alternating chemo-radiotherapy in locally advanced head and neck cancer patients. PATIENTS AND METHODS: From August 1993 to April 1998 at the Division of Medical Oncology of Parma, 48 consecutive patients were observed, and 38 (79%) started the Merlano chemo-radiotherapy. The characteristics of the patients were: males (32, 84%); median age, 57 years; PS <2 (32, 84%). The primary sites were the oropharynx (18, 47%), oral cavity (8, 21%), hypopharynx (7, 19%), larynx (5, 13%); stage IV disease was present in 29 (76%) patients. Twenty-five (66%) patients were married, and 24 (63%) resided outside of the city. RESULTS: The compliance was very low: 21 patients (55%) performed all the programmed cycles of chemotherapy, whereas only 5 patients (13%) performed the chemo-radiotherapy at full doses without any delay. The objective responses were 3 (8%) complete and 21 (55%) complete plus partial responses. Failures were 2 (5%) stable disease and 2 (5%) progressive disease, and the response was not assessable in 10 (26%). The median duration of the response was 8 months. The median overall survival and the time to progression were 18 and 13 months, respectively; the 5-year overall and relapse-free survival were 36% and 26%, respectively. Nine (24%) patients were still alive as of August 30, 2001, 8 (21%) of them without progression. Twenty-six patients (68%) died with a local-regional relapse. One patient (3%) died for a second cancer. Grade 3-4 hematologic toxicity was leukopenia (n = 25, 66%) and thrombocytopenia (n = 9, 24%); grade 3-4 non-hematologic toxicity was diarrhea (n = 3, 8%) and mucositis (n = 2, 5%). Two patients (5%) died for intestinal infarction and perforation possibly related to treatment. CONCLUSIONS: Compliance to the chemo-radiotherapy was very poor. The response rate was lower than that reported in clinical trials, whereas overall survival was comparable. The alternating chemo-radiotherapy is a very complex treatment that cannot be easily applied in clinical practice; a careful selection of patients is mandatory not only considering oncologic and medical criteria, but also the level of awareness of the patient and his family.     

老年局部晚期食管癌同步放化疗与单纯放疗的疗效比较

目的：比较老年局部晚期食管癌患者采用同步放化疗（CRT）和单纯放疗（RT）的疗效和急性不良反应。方法：回顾性分析2010年1月—2016年1月于河北医科大学第四医院就诊,年龄>70岁的82例老年局部晚期食管癌患者。比较CRT和RT两个治疗组间的完全缓解率（CRR）、部分缓解率（PRR）、疾病缓解率（DCR）、无进展生存期（PFS）、总生存期（OS）和急性不良反应,并分析食管癌预后的影响因素。结果：CRT组患者的CRR （33.3%）明显高于RT组（14.5%,P=0.049）,两组之间PRR和DCR的差异无统计学意义（P=0.058,0.064）。CRT组患者的中位PFS及PFS≥1、2、3年的患者比例均显著高于RT组（P=0.007）。CRT组患者的中位OS及OS≥1、2、3年的患者比例亦显著高于RT组（P=0.012）。单因素分析显示不同治疗方案、CRR是PFS和OS的影响因素。多因素分析显示CRR为PFS的独立预后影响因素,不同治疗方案、CRR是OS的独立预后影响因素（均为P <0.05）。CRT组患者的部分急性不良反应有恶心、呕吐、白细胞减少症、血小板减少症,发生率均高于RT组（均为P <0.05）。结论：同步放化疗可作为老年局部晚期食管鳞癌患者的治疗方案,且疗效优于单纯放疗,但仍需密切关注患者的不良反应。     

Radiation therapy is well tolerated and produces excellent control rates in elderly patients with locally advanced head and neck cancers

PurposeManagement of locally advanced head and neck cancer (LAHNC) in the elderly is challenging due to multiple co-morbidities, poor organ function and performance status. The aim of this study was to evaluate efficacy of radiation therapy (RT) in elderly patients, defined as 65 years and older, with high-risk LAHNC.Materials and methodsAn IRB approved retrospective chart review of elderly patients was performed, of whom 73 patients were selected for analysis. The stages included were II–IV. Sites included were oropharynx, oral cavity, larynx, salivary gland, nasopharynx, nasal cavity, paranasal sinus, hypopharynx and unknown primary.ResultsMedian age was 74 years. Thirty-nine (53%) patients received concurrent chemotherapy. Median time to completion of RT was 53 days. Median external beam radiotherapy (EBRT) dose was 66 Gy. With a median follow-up of 24 months, overall local control (LC) was 80% and distant metastasis (DM) was 12%. Sixty patients (82%) were alive at the time of study. Two-year overall survival (OS) was 96% (95% CI = 87%, 99%). Chemotherapy did not improve LC [80% (chemo) vs. 79% (no chemo), p = 0.88] or DM [11% (chemo) vs. 14% (no chemo), p = 0.73]. Interestingly, patients receiving RT using intensity-modulated radiation therapy (IMRT) had a significantly higher rate of LC vs. three-dimensional conformal radiotherapy (3DCRT) (94% vs. 68%, respectively, p = 0.008). Grade 2/3 toxicity was seen in 70/73 (96%) patients while grade 4 toxicity was seen in three patients (4%).ConclusionElderly patients with LAHNC have high rates of LC and OS. Prospective studies can reveal more insight into this increasingly important clinical problem in elderly patients.     

p53 mutations and overexpression in locally advanced breast cancers.

Alterations in the p53 gene were analysed in 39 patients with locally advanced breast cancers (LABCs) (stage III-IV) with inflammatory signs in most cases (UICC stage T4d = 32 patients) by molecular and immunohistochemical (IHC) approaches. All patients were included in the same therapy protocol. Using polymerase chain reaction (PCR) and a single-strand conformational polymorphism migration technique (SSCP), the presence of mutations in exons 2-11, covering the entire coding sequence of the p53 gene, was evaluated. Using the mouse specific anti-human p53 monoclonal antibody (PAb 1801), we also looked for overexpression of the p53 protein in tissue sections. In 16 cases shifted bands were reproducibly identified by PCR-SSCP, and all but one (localised to exon 10) were in exons 5-8, the usual mutational hotspots. Fifteen of these 16 samples were sequenced and 14 of the suspected mutations (36%) were confirmed. Most of them (12) were single nucleotide substitutions, and transitions were more frequent (eight cases) than transversions (four cases). Fourteen of the tumour samples were positively stained with the monoclonal antibody PAb 1801, 11 with nuclear staining only, two with mixed cytoplasmic and nuclear staining and one with cytoplasmic staining only. Staining patterns were very heterogeneous in terms of the percentage of positive cells (10-75%) and their distribution in the tissue section (isolated foci or dispersed cells). In 11 of the 14 mutated cases a positive immunostaining was observed. The presence of a p53 mutation was significantly associated with larger tumour diameter (chi 2 = 7.490, P = 0.0062) and the presence of clinical metastases (stage IV) (chi 2 = 10.113, P = 0.0015). A non-statistically significant trend of association was observed between p53 mutation, negative oestrogen receptors and lower response rate to therapy. Our results in this group of patients and the heterogeneity of the staining of tumour cells in tissue sections suggest that p53 mutations could be a late event in this non-familial form of breast cancer.     

Definitive radiotherapy for uterine cervix cancer: long term results for patients treated in the period from 1998 till 2002 at the Institute of Oncology Ljubljana

Background

The aim of this retrospective study was to analyse results of the two-dimensional (2D) uterine cervix cancer treatment at the Institute of Oncology Ljubljana from 1998 till 2002, before the three-dimensional (3D) approach was introduced in our clinical practice.

Methods

Ninety-eight patients with the following FIGO stage distribution were analysed: 10% IB, 7% IIA, 37% IIB, 4% IIIA and 42% IIIB. The influence of age, haemoglobin level, histology, grade, stage, lymph node status, cumulative point A dose, and an overall treatment time on the survival and local control (LC) were evaluated. Acute and late side effects were assessed.

Results

Five and 8-year overall survival (OS), disease specific survival (DSS) and LC rate were as follows: 47.2% and 43.0%, 54.7% and 53.4%, 74.9% and 72.5%, respectively. Point A dose and histology of the tumour influenced OS, positive lymph nodes DSS and point A dose LC rate. Probability of grade three and four late complications in the first five years was 7.1% for gastrointestinal tract and 3.3% for genitourinary system and vagina.

Conclusions

Point A dose was independent predictor of OS and LC rate, lymph node status predicted DSS, while histology of the tumour influenced OS.     

The prognostic value of anaemia at different treatment times in patients with locally advanced head and neck cancer treated with surgery and postoperative radiotherapy

AimsWe report a retrospective mono-institutional analysis of anaemia (<12 g/dl) at different treatment times (preoperative, postoperative, before radiotherapy and nadir levels during radiotherapy) in head and neck cancer patients treated with surgery and postoperative radiotherapy. The study objective was to determine whether, and at which time points, anaemia had a significant effect on the end points overall survival and local recurrence-free survival (LRFS).Materials and methodsThe end points for the statistical analysis in 130 patients were LRFS and overall survival. A univariate analysis (Log-rank test) was carried out on the following variables with potential end point-related impact: gender, T, N, G, American Joint Committee on Cancer (AJCC) stage, tumour site, resection status, overall treatment time (OTT), radiotherapy treatment time (RTT) and preoperative, postoperative, pre-radiotherapy and nadir levels of haemoglobin during radiotherapy. Individual variables with a significant effect (P = 0.05) were then subjected to multivariate Cox regression analysis.ResultsThe median overall survival was 59 months. The univariate analysis showed that AJCC stage (P = 0.0268), resection status (P = 0.0407), preoperative haemoglobin level (P = 0.0087), postoperative haemoglobin level (P = 0.0035), RTT (P = 0.0042) and OTT (P = 0.0343) significantly influenced overall survival. OTT (P = 0.0130) and postoperative haemoglobin (P = 0.0243) had a significant effect on LRFS. The multivariate Cox regression analysis showed postoperative haemoglobin <12 g/dl and OTT > 100 days to be independent negative prognostic factors for both end points.ConclusionsPostoperative acute anaemia <12 g/dl and an OTT > 100 days were independent negative prognostic factors for LRFS and overall survival in patients with head and neck cancer treated with surgery and postoperative radiotherapy.