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Claire Lemanski

Publications and source records attributed to Claire Lemanski.

At least 19 recordsLinked to original sources
PubMed2006

Impact of swallowing therapy on aspiration rate following treatment for locally advanced head and neck cancer.

This study examines the efficacy of swallowing therapy in cancer-free patients who developed aspiration following treatment for locally advanced head and neck cancer. The records of 41 patients who underwent swallowing therapy for aspiration were reviewed. All patients were cancer free at a median follow-up of 25 months (6-150 months). Their treatment were respectively chemoradiation (24), and postoperative radiation (17). All patients had two or more modified barium swallow (MBS). Dysphagia severity was graded from 1 to 7. Dysphagia grade was compared before and following swallowing therapy. Before swallowing therapy, there were 16 grade 5 (trace aspiration), and 25 grade 6-7 (severe aspiration). In the chemoradiation group, there were nine grade 5, five grade 6, and 10 grade 7. Corresponding numbers for the postoperative group were: seven grade 5, seven grade 6, and three grade 7. Following swallowing therapy, there were six grade 3, seven grade 4, 10 grade 5, six grade 6, and 12 grade 7. In the chemoradiation group, there were four grade 3, three grade 4, four grade 5, five grade 6, and eight grade 7. In the postoperative group, there were two grade 3, four grade 4, six grade 5, one grade 6, and four grade 7. Overall, 13 patients (32%) had improvement of their dysphagia severity. Seven of them were in the chemoradiation group (29%), and six (35%) were in the postoperative group. Among 25 patients who presented with grade 6-7 aspiration, only nine (36%) improved to grade 5 or less. Four of them (27%) were in the chemoradiation group, and five (29%) were in the postoperative group. Swallowing therapy is effective to improve dysphagia severity and reduce the need for tube feedings. However, a significant number of patients still suffered from chronic severe aspiration. New strategies must be devised to improve their outcome.

Adult↗
PubMed2006

Aspiration rate following chemoradiation for head and neck cancer: an underreported occurrence.

BACKGROUND AND PURPOSE: We would like to assess the prevalence of aspiration before and following chemoradiation for head and neck cancer. PATIENTS AND METHODS: We reviewed retrospectively the Modified Barium Swallow (MBS) in 63 patients who underwent concurrent chemotherapy and radiation for head and neck cancer. MBS was performed prior to treatment to determine the need for immediate gastrostomy tube placement. MBS was repeated following treatment to assess the safety of oral feeding prior to removal of tube feeding. All patients were cancer free at the time of the swallowing study. No patient had surgery. Dysphagia severity was graded on a scale of 1-7. Tube feedings were continued if patients were diagnosed to have severe aspiration (grade 6-7) or continued weight loss. Patients with abnormal swallow (grade 3-7) received swallowing therapy following MBS. RESULTS: Before treatment, there were 18 grade 1, 18 grade 2, 9 grade 3, 8 grade 4, 3 grade 5, 3 grade 6, and 4 grade 7. Following chemoradiation, at a median follow-up of 2 months (1-10 months), one patient had grade 1, eight patients had grade 2, nine patients had grade 3, eight patients had grade 4, 13 patients had grade 5, seven patients had grade 6, and 11 patients had grade 7. Six patients died from aspiration pneumonia (one before, three during, and two post-treatment), and did not have the second MBS. Overall, 37/63 (59%) patients developed aspiration, six of them (9%) fatal. If we excluded the 10 patients who had severe aspiration at diagnosis and the six patients who died from pneumonia, the prevalence of severe aspiration was 33% (21/63). CONCLUSIONS: Aspiration remained a significant morbidity following chemoradiation for head and neck cancer. Its prevalence is underreported in the literature because of its often silent nature. Diagnostic studies such as MBS should be part of future head and neck cancer prospective studies to assess the prevalence of aspiration, and for rehabilitation.

Aged↗
PubMed2006

Phase III randomized trial of very accelerated radiation therapy compared with conventional radiation therapy in squamous cell head and neck cancer: a GORTEC trial.

PURPOSE: With the aim to increase the dose intensity of radiation therapy (RT), and subsequently the locoregional control rate, a very accelerated RT regimen was compared with conventional RT in a series of patients with head and neck squamous cell carcinoma (HNSCC). PATIENTS AND METHODS: Between 1994 and 1998, 268 patients with T3 or T4, N0 to N3 HNSCC (staged by 1997 International Union Against Cancer criteria) that was not eligible for surgery were randomly assigned to receive either conventional RT, delivering 70 Gy in 7 weeks to the primary tumor and 35 fractions of 2 Gy over 49 days, or to receive very accelerated RT, delivering 62 to 64 Gy in 31 to 32 fractions of 2 Gy over 22 to 23 days (2 Gy/fraction bid). RESULTS: The most common tumor site was the oropharynx and most of the patients (70%) had T4 and N1 to N3 tumors in 72% of patients. The main patient and tumor characteristics were well-balanced between the two arms. The median total doses were 63 Gy (accelerated) and 70 Gy (conventional), with a median overall time of 22 days and 48 days, respectively. Acute mucositis was markedly increased in the accelerated-RT arm (P < .001). The locoregional control rate was improved by 24% at 6 years with accelerated RT. In contrast, disease-free survival and overall survival were not significantly different between the two arms. There was no difference in late effects between the two arms. CONCLUSION: The very accelerated RT regimen was feasible and provided a major benefit in locoregional control but had a modest effect on survival.

Carcinoma, Squamous Cell↗
PubMed2006

Dysphagia severity following chemoradiation and postoperative radiation for head and neck cancer.

OBJECTIVE: The purpose of the study is to evaluate dysphagia severity following chemoradiation and postoperative radiation for head and neck cancer, and particularly the aspiration risk because of its potential life-threatening consequence. MATERIALS AND METHODS: We reviewed retrospectively the modified barium swallow (MBS) results in 110 patients who complained of dysphagia following chemoradiation (57) and postoperative radiation (53) of their head and neck cancer. Patients were selected if they were cancer free at the time of the swallowing study. Dysphagia severity was graded on a scale of 1-7. Patients were grouped according to the dysphagia severity: mild (grades 2-3), moderate (grades 4-5), and severe (grades 6-7). RESULTS: Mean and median dysphagia grades were 4.84/5 and 4.12/4 for chemoradiation and postoperative radiation respectively. The mean difference between the two groups is statistically significant (p=0.02). Mild dysphagia occurred in 13 patients (22%) of the chemoradiation group and 17 (32%) of the postoperative group. Corresponding number for the moderate group was 25 (43%) and 25 (48%), respectively. Severe dysphagia was significant in the chemoradiation group (34%) compared to the postoperative group (19%). However, the difference was not statistically significant (p=0.29). There was a higher proportion of patients with large tumor (T3-T4) in the chemoradiation group who developed severe dysphagia. CONCLUSION: Dysphagia remained a significant morbidity of chemoradiation and postoperative radiation for head and neck cancer. Dysphagia may be more severe in the chemoradiation group because of the higher proportion of patients with large tumor, the high radiation dose, and a high number of oropharyngeal tumors. Aspiration occurred in both groups. Diagnostic studies such as MBS should be part of future head and neck cancer prospective studies to assess the prevalence of aspiration, as it may be silent.

Aged↗
PubMed2006

Intraoperative radiotherapy given as a boost for early breast cancer: long-term clinical and cosmetic results.

PURPOSE: The standard radiotherapy (RT) of breast cancer consists of 50 Gy external beam RT (EBRT) to the whole breast followed by an electron boost of 10-16 Gy to the tumor bed, but this has several cosmetic disadvantages. Intraoperative radiotherapy (IORT) could be an alternative to overcome these. METHODS AND MATERIALS: We evaluated 50 women with early breast cancer operated on in a dedicated IORT facility. Median dose of 10 Gy was delivered using 9-MeV electron beams. All patients received postoperative EBRT (50 Gy in 2 Gy fractions). Late toxicity and cosmetic results were assessed independently by two physicians according to the Common Terminology Criteria for Adverse Event v3.0 grading system and the European Organization for Research and Treatment of Cancer questionnaires. RESULTS: After a median follow-up of 9.1 years (range, 5-15 years), two local recurrences were observed within the primary tumor bed. At the time of analysis, 45 patients are alive with (n = 1) or without disease. Among the 42 disease-free remaining patients, 6 experienced Grade 2 late subcutaneous fibrosis within the boost area. Overall, the scores indicated a very good quality of life and cosmesis was good to excellent in the evaluated patients. CONCLUSION: Our results confirm that IORT given as a boost after breast-conserving surgery is a reliable alternative to conventional postoperative fractionated boost radiation.

Adult↗
PubMed2006

French multicenter phase III randomized study testing concurrent twice-a-day radiotherapy and cisplatin/5-fluorouracil chemotherapy (BiRCF) in unresectable pharyngeal carcinoma: Results at 2 years (FNCLCC-GORTEC).

BACKGROUND: Unresectable carcinomas of the oropharynx and hypopharynx still have a poor long-term prognosis. Following a previous phase II study, this phase III multicenter trial was conducted between November 1997 and March 2002. METHODS: Nontreated, strictly unresectable cases were eligible. Twice-daily radiation: two fractions of 1.2 Gy/day, 5 days per week, with no split (D1-->D46). Total tumor doses: 80.4 Gy/46 day (oropharynx), 75.6 Gy/44 day (hypopharynx). Chemotherapy (arm B): Cisplatin 100 mg/m2 (D1, D22, D43); 5FU, continuous infusion (D1-->D5), 750 mg/m2/day cycle 1; 430 mg/m2/day cycles 2 and 3. RESULTS: A total of 163 evaluable patients. Grade 3-4 acute mucositis 82.6% arm B/69.5% arm A (NS); Grade 3-4 neutropenia 33.3% arm B/2.4% arm A (p < 0.05). Enteral nutrition through gastrostomy tube was more frequent in arm B before treatment and at 6 months (p < 0.01). At 24 months, overall survival (OS), disease-free survival (DFS), and specific survival (SS) were significantly better in arm B. OS: 37.8% arm B vs. 20.1% arm A (p = 0.038); DFS: 48.2% vs. 25.2% (p = 0.002); SS: 44.5% vs. 30.2% (p = 0.021). No significant difference between the two arms in the amount of side effects at 1 and 2 years. CONCLUSION: For these unresectable cases, chemoradiation provides better outcome than radiation alone, even with an "aggressive" dose-intensity radiotherapy schedule.

Adult↗
PubMed2005

Combined radiotherapy, 5-fluorouracil continuous infusion and weekly oxaliplatin in advanced rectal cancer: a phase I study.

The aim of this study was to determine the maximum-tolerated dose (MTD) of weekly oxaliplatin combined with 5-fluorouracil (5FU) continuous infusion administered concomitantly with fractionated radiotherapy in patients presenting advanced rectal cancer. Forty-three patients with rectal cancer (stage T3/T4 (n = 24), metastatic (n = 17) and 2 with local recurrence), were included. The radiotherapy dose delivered was 45 Gy over 5 weeks (1.8 Gy/fraction/day, 5 days per week). The initial weekly oxaliplatin dosage was 30 mg/m2 and the 5FU dosage 150 mg/m2/d. The oxaliplatin and 5FU doses were escalated. Eight dose levels were tested. At dose level 8 (oxaliplatin 80 mg/m2, 5FU 225 mg/m2/d), 2 patients out of 4 presented dose-limiting toxicity (severe diarrhoea with dehydration and fatal shock, rectovesical fistula). At dose level 7, 2 further patients presented with grade 3 diarrhoea. The main toxicity of the combination was diarrhoea. The hematological and neurological toxicities were not severe and were not dose-limiting. Out of the 30 patients undergoing surgery, 4 (13.3%) presented with pathological complete response and 4 (13.3%) only presented with microscopic residual disease. The results from this study enabled determination of the recommended weekly oxaliplatin dose (60 mg/m2) combined with 5FU continuous infusion (225 mg/m2) and fractionated radiotherapy (45 Gy) in the pre-operative treatment of advanced rectal cancer. The good safety profile of the regimen, associated with promising results in terms of histological response, suggest that the regimen could be developed in future phase II/III studies.

Adult↗
PubMed2005

Prognostic impact of epidermal growth factor receptor (EGFR) expression on loco-regional recurrence after preoperative radiotherapy in rectal cancer.

BACKGROUND: Epidermal growth factor receptor (EGFR) represents a major target for current radiosensitizing strategies. We wished to ascertain whether a correlation exists between the expression of EGFR and treatment outcome in a group of patients with rectal adenocarcinoma who had undergone preoperative radiotherapy (RT). METHODS: Within a six-year period, 138 patients underwent preoperative radiotherapy and curative surgery for rectal cancer (UICC stages II-III) at our institute. Among them, 77 pretherapeutic tumor biopsies were available for semi-quantitative immunohistochemical investigation evaluating the intensity and the number (extent) of tumor stained cells. Statistical analyses included Cox regression for calculating risk ratios of survival endpoints and logistic regression for determining odds ratios for the development of loco-regional recurrences. RESULTS: Median age was 64 years (range: 30-88). Initial staging showed 75% and 25% stage II and III tumors, respectively. RT consisted of 44-Gy pelvic irradiation in 2-Gy fractions using 18-MV photons. In 25 very low-rectal-cancer patients the primary tumor received a boost dose of up to 16 Gy for a sphincter-preservation approach. Concomitant chemotherapy was used in 17% of the cases. All patients underwent complete total mesorectal resection. Positive staining (EGFR+) was observed in 43 patients (56%). Median follow-up was 36 months (range: 6-86). Locoregional recurrence rates were 7 and 20% for EGFR extent inferior and superior to 25%, respectively. The corresponding locoregional recurrence-free survival rate at two years was 94% (95% confidence interval, CI, 92-98%) and 84% (CI 95%, 58-95%), respectively (P = 0.06). Multivariate analyses showed a significant correlation between the rate of loco-regional recurrence and three parameters: EGFR extent superior to 25% (hazard ratio = 7.18, CI 95%, 1.17-46, P = 0.037), rectal resection with microscopic residue (hazard ratio = 6.92, CI 95%, 1.18-40.41, P = 0.032), and a total dose of 44 Gy (hazard ratio = 5.78, CI 95%, 1.04-32.05, P = 0.045). CONCLUSION: EGFR expression impacts on loco-regional recurrence. Knowledge of expression of EGFR in rectal cancer could contribute to the identification of patients with an increased risk of recurrences, and to the prediction of prognosis.

Adult↗
PubMed2005

[Anemia in head and neck cancers].

Anemia is very common in head and neck cancer patients, and seems to be correlated with intratumoral hypoxia. Anemia is one of the main prognostic factors of locoregional recurrence and, in some studies, of poor survival. Blood transfusions and human recombinant erythropoietin (rHuEPO) are the two main methods used in clinical practice to correct hemoglobin level during curative treatment. Blood transfusions were rarely evaluated, and did not influence locoregional control of patients treated with radiotherapy with or without chemotherapy. Retrospective studies evaluating combined treatment of rHuEPO and radiotherapy reported positive impact on locoregional recurrence and actuarial survival. Since the end of 2003, this approach is a matter for debate after the negative results of a prospective randomized study on progression-free survival concerning head and neck cancer patients treated with definitive or postoperative external radiotherapy with or without rHuEPO. Although many biases were reported against this publication, several questions are to be answered in the near future. Among them, erythropoietin receptor expression and activation on tumour cell seem to be the more appropriate explanation of these negative results. In October 2004, preliminary results of the RTOG 99-03 study have been presented at the Astro annual meeting in Atlanta. This prospective randomized trial was designed to determine if concurrent rHuEPO administration (40,000 units) with radiotherapy (with or without chemotherapy) could improve locoregional control in non-operative head and neck cancers. In the rHuEPO arm, haemoglobin level was significantly increased compared with control arm. However, the addition of concurrent rHuEPO to definitive radiotherapy did not improve locoregional control or survival for mildly/moderately anemic patients with head and neck squamous cell carcinoma. Future clinical trials using biological markers are thus imperative to target which patients could benefit from these molecules.

Anemia↗
PubMed2005

[Recent data on lobular neoplasia of the breast: the pathologist's opinion].

Lobular neoplasia is the new WHO terminology that encompasses the so-called lobular carcinoma in situ and atypical lobular hyperplasia. Besides the classical forms, particular variants have been described, which are mammographically detectable with distinct histologic patterns and behaviour. These variants are characterized by pleomorphic cells, necrosis with calcifications and may be associated to an invasive lobular carcinoma. Their clinical issue looks more like a preinvasive lesion than a marker of increased risk. Thus, their identification on biopsy requires a surgical reexcision. Hybrid forms, sharing a mixed lobular and ductal morphology and phenotype, have also been mentionned. Despite a lack of prognostic evaluation, it seems logical to recommend a subsequent surgical investigation when they are observed. Classical forms are usually managed by simple follow-up, although this attitude does not make a consensus among pathologists. Lobular neoplasia are not all indolent lesions and belong to an heterogeneous group that percutaneous guided biopsies have emphasized. They should be managed in a pluridisciplinar way and correctly diagnosed on percutaneous biopsies as well as surgical specimens.

Biopsy↗
PubMed2005

Surgery for esophageal cancer after concomitant radiochemotherapy: oncologic and functional results.

The aim of this study was to evaluate the results of surgery after preoperative radiochemotherapy (PRCT) for esophageal cancer. This retrospective study included 88 patients scan between 1992 and 2000. The median follow-up was 55.7 months (3.3-104.1 months). Surgical mortality was 15.9%. Multivariate analysis found that the following were risk factors for surgical mortality: gamma-glutamyltransferase level > 75 UI/ml (p = 0.007), weight loss = 10% (p = 0.05), and digestive toxicity World Health Organization grade III or IV during PRCT (p = 0.019). The median overall survival was 24.9 months. The 5-year overall survival (OS) and disease-free survival (DFS) were, respectively, 33.1% and 33.2%. Complete responder patients had a 71.8% 5-year OS (p = 0.01) and a 71.8% 5-year DFS (p = 0.009). The rate of recurrence was 37.5%. Multivariate analysis found that female gender (p = 0.03), weight loss = 10% (p = 0.03), preoperative computed tomography scan bronchial contact (p = 0.01), and N+ status (pN+) at pathology examination (p = 0.0001) were predictors of poor oncologic results. Patients with high preoperative risk of surgical mortality need to be selected for intensive perioperative management. In association with surgery, PRCT improves the local control, DFS, and OS of responder patients. Morphologic evaluation for staging esophageal cancer in predicting the pathologic response after PRCT is poor or controversial. Only surgical resection can provide accurate prognostic information for staging esophageal cancer and improving local control.

Adenocarcinoma↗
PubMed2005

[Standards, Options and Recommendations for the management of ductal carcinoma in situ of the breast (DCIS): update 2004].

The " Standards, Options and Recommendations " (SOR) project, started in 1993, is a collaboration between the Federation of French Cancer Centres (FNCLCC), the 20 French cancer centres, and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. Objectives : To update the Standards, Options and Recommendations clinical practice guidelines for the management of ductal carcinoma in situ of the breast (DCIS). Methods : The working group identified the questions requiring up-dating from the previous guideline. Medline(r) and Embase(r) were searched using specific search strategies from year 1996 to year 2003. In addition several Internet sites were searched in October 2002. Results : Clinical guidelines have been defined for the management of diagnosis, treatment, follow-up, and treatment of recurrence of DCIS. The issue of hormone replacement therapy has also been addressed in the context of DCIS.

Breast Neoplasms↗
PubMed2005

[Clinical Practice Guidelines 2004. Standards, Options and Recommendations for the management of patient with adenocarcinoma of the stomach: radiotherapy (therapeutic evaluation)].

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of French Cancer Centers (FNCLCC), the 20 French regional cancer centers, and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. OBJECTIVES: To elaborate clinical practice guidelines for patients with stomach adenocarcinoma. These recommendations cover the diagnosis, treatment and follow-up of these tumors. METHODS: The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. The Standards, Options and Recommendations are thus based on the best available evidence and expert agreement. RESULTS: This guidelines presents the synthesis of the data concerning the evaluation of the therapeutic ones. The main questions concern the type of gastrectomy to realize (Total Gastrectomy or gastrectomy subtotal), the extent of the lymphadenectomy (D2, D3 versus D1, D3, D2 versus D4) and the role of postoperative chemotherapy and adjuvant concomitant chemoradiotherapy.

Adenocarcinoma↗
PubMed2002

Breast-conserving therapy for ductal carcinoma in situ of the breast: the French Cancer Centers' experience.

PURPOSE: To assess the long-term outcome for women with ductal carcinoma in situ of the breast treated in current clinical practice by conservative surgery with or without definitive breast irradiation. METHODS AND MATERIALS: We analyzed 705 cases of ductal carcinoma in situ treated between 1985 and 1995 in nine French regional cancer centers; 515 underwent conservative surgery and radiotherapy (CS+RT) and 190 CS alone. The median follow-up was 7 years. RESULTS: The 7-year crude local recurrence (LR) rate was 12.6% (95% confidence interval [CI] 9.4-15.8) and 32.4% (95% CI 25-39.7) for the CS+RT and CS groups, respectively (p <0.0001). The respective 10-year results were 18.2% (95% CI 13.3-23) and 43.8% (95% CI 30-57.7). A total of 125 LRs occurred, 66 and 59 in the CS+RT and CS groups, respectively. Invasive or microinvasive LRs occurred in 60.6% and 52% of the cases in the same respective groups. The median time to LR development was 55 and 41 months. Nine (1.7%) and 6 (3.1%) nodal recurrences occurred in the CS+RT and CS groups, respectively. Distant metastases occurred in 1.4% and 3% of the respective groups. Patient age and excision quality (final margin status) were both significantly associated with LR risk in the CS+RT group: the LR rate was 29%, 13%, and 8% among women aged < or =40, 41-60, and > or =61 years (p <0.001). Even in the case of complete excision, we observed a 24% rate of LR (6 of 25) in women <40 years. Patients with negative, positive, or uncertain margins had a 7-year crude LR rate of 9.7%, 25.2%, and 12.2%, respectively (p = 0.008). RT reduced the LR rate in all subgroups, especially in those with comedocarcinoma (17% vs. 59% in the CS+RT and CS groups, respectively, p <0.0001) and mixed cribriform/papillary tumors (9% vs. 31%, p <0.0001). In the multivariate Cox regression model, young age and positive margins remained significant in the CS+RT group (p = 0.00012 and p = 0.016). Finally, the relative LR risk in the CS+RT group compared with the CS group was 0.35 (95% CI 0.25-0.51, p = 0.0001). Subsequent contralateral breast cancer occurred in 7.1% and 7.5% of the patients in the CS+RT and CS groups, respectively. CONCLUSION: Despite the absence of randomization, our results are extremely consistent with the updated National Surgical Adjuvant Breast Project B17 and European Organization for Research and Treatment of Cancer 10853 trials. We also noted that the LR risk was very high in women <40 years and/or in the case of incomplete excision.

Adult↗
PubMed2002

Restorative and nonrestorative surgery for low rectal cancer after high-dose radiation: long-term oncologic and functional results.

PURPOSE: This prospective, nonrandomized study evaluates, with a seven-year median follow-up, the morbidity and the functional and oncologic results of conservative surgery after high-dose radiation for cancer of the lower third of the rectum of patients who would otherwise have undergone abdominoperineal resection. METHODS: Between June 1990 and June 1996, 43 patients with distal rectal adenocarcinoma were treated by preoperative radiotherapy (40 + 20 Gy delivered with three fields) and curative surgery. The mean distance from the anal verge was 50 (range, 25-60) mm, and none of the tumors was fixed (15 percent T2N0, 53 percent T3N0, 32 percent T3N1). RESULTS: Postoperative mortality (2 percent) and morbidity (35 percent) were not increased by high-dose preoperative radiation. Conservative surgery was done in 30 patients (70 percent: 26 coloanal anastomoses and 4 low stapled anastomoses). After conservative surgery, long-term functional results showed 30 percent complete continence and 20 percent serious incontinence. Four patients had local recurrence as first development (13 percent). The seven-year overall survival rate was 53 percent, 62 percent after conservative surgery and 31 percent after abdominoperineal resection. The univariate analysis underscores the tumor response impact on long-term survival (pT<3 = 81 percent; pT3 = 35 percent; P = 0.0008). CONCLUSIONS: These long-term results confirm the feasibility of conservative surgery for low rectal carcinoma after high-dose radiation. A prospective multicentric trial began in France in June 1996 to evaluate the reproducibility of these results.

Adenocarcinoma↗
PubMed2002

Treatment of unresectable, locally advanced pancreatic adenocarcinoma with combined radiochemotherapy with 5-fluorouracil and cisplatin.

INTRODUCTION: Adenocarcinoma of the pancreas remains one of the most difficult malignancies to treat. Its incidence has steadily increased over the past four decades, and its prognosis is still dismal. AIM To assess tumor control and the palliative benefit of 5-fluorouracil (5-FU), cisplatin (CDDP), and radiotherapy in patients with advanced pancreatic cancer. METHODOLOGY: Systemic chemotherapy consisted of 5-FU (600 mg/m ), given as a 22-hour infusion on days 1 to 5, and CDDP (100 mg/m ), given as a 90-minute infusion on day 2. Treatment courses were repeated identically on day 21. Radiotherapy was delivered using megavolt irradiation of 25-MV photons with a two- or four-field isocentric technique. RESULTS: Twenty-seven patients were treated with this radiochemotherapy (RCT). Twenty-one patients (78%) completed initial treatment. The median dose of radiation therapy delivered was 42.5 Gy. At the time of evaluation (1 month after the end of the RCT), no grade 4 (WHO) toxicity was observed; 12 patients had improved or stable body weight; pain was improved for 20 patients, with 11 experiencing no pain; and analgesic consumption decreased for 18 patients, of whom 11 stopped intake. The clinical benefit response was 7/27 (26%). Median survival and time to progression were, respectively, 9 and 4.4 months. CONCLUSION: This RCT regimen had a good impact on clinical benefit in locally advanced pancreatic carcinoma, without severe side effects.

Adenocarcinoma↗
PubMed2002

[Gemcitabine and ionizing radiations: radiosensitization or radio-chemotherapy combination].

Gemcitabine is a pyrimidine analog which has demonstrated antitumoral activity in a variety of solid tumors including bladder, non-small cell lung and pancreatic cancers. Gemcitabine is a potent radiosensitizer of human tumor cells. This review summarizes preclinical studies designed to elucidate the mechanism of action of gemcitabine with ionizing radiation. Phase I-II ongoing trials of combination of radiation therapy and gemcitabine are trying to determine the optimal dose and schedule which could be used in daily clinical activity. The mechanism of radiosensitization is thought to be simultaneously gemcitabine-induced dATP (deoxyadenosine triphosphate) depletion and cell cycle redistribution into the S phase. Although there are no real study which has proven supra-additive combination, the recent acute side effects in several clinical studies oblige physicists to determine with precision the maximum tolerated dose of gemcitabine in association with ionizing radiation. Radiosensitization conditions can be obtained either with a long exposition to a low concentration or a short exposition to a high concentration. Radiation sensitivity begin to be detected four hours after treatment for 48 hours. A dose about 100 mg/m2/week of gemcitabine could be used with radiation therapy according to recent phase I results. This limiting dose is approaching to a radiosensitization context where the effect of one agent is increased by another agent which is inactive or poorly active for the effect under consideration. In this type of regimen, the two modalities do interact with a frequent inhibition of recovery from potentially lethal damage and a probably increase of late side effects of radiation therapy. In contrast, radio-chemotherapy combination is used for a therapeutic advantage when the drug by itself is active against the tumor but does not enhance late side effects of radiation on the critical normal tissues within the irradiated volume. Gemcitabine surely is a strong radiosensitizer even at low doses with future extended combined modality therapeutic indications. The ultimate goal of combined treatments should be an increased therapeutic ratio.

Adenosine Triphosphate↗