[Prognostic factors for patients with brain metastases]. / Facteurs pronostiques des métastases cérébrales.

Approximately 20 to 40 % of patients with metastatic cancer will develop brain metastases (BM) during the disease course. Whole-brain radiation therapy (WBRT) is considered the standard treatment for most patients, particularly those with extensive intracranial disease, providing symptom relief and increasing median and overall survival. Despite WBRT, the prognosis for the general population of patients with BM remains poor, with a median survival time of approximately five months. Several studies have examined the relative contribution of patient characteristics to survival and have attempted to identify subgroups of patients with substantially different outcomes in order to tailor therapy and to influence the design, stratification and interpretation of future clinical trials. Here, we review the main prognostic factors and prognostic scores in patients with BM and the value and limits of these prognostic scores in clinical practice.

Identification of new candidate therapeutic target genes in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a subgroup of breast cancer that is negative for estrogen and progesterone receptor and ERBB2 protein expression. It is characterized by its aggressive behavior and by the lack of targeted therapies. To identify new therapeutic targets in TNBC, we used real-time quantitative RT-PCR to analyze 63 TNBC samples in terms of their mRNA expression of 26 genes coding for the major proteins currently targeted by drugs used to treat other cancers or undergoing clinical trials in breast cancer. Six of the 26 genes tested (VEGFA, SRC, PARP1, PTK2, RAF1, and FGFR3) were significantly upregulated in 13% to 46% of the TNBCs. None of the 6 genes was specifically upregulated in the TNBCs compared with 3 other classical breast tumor subtypes. No association was observed between overexpression of these 6 genes (except for FGFR3) and PIK3CA mutation status. These results confirm the interest of targeting VEGFA and PARP1 in ongoing clinical trials in TNBC patients and also identify new target genes (SRC, PTK2, RAF1, and FGFR3). Clinical trials could be initiated easily with existing drugs. Our results also suggest that these target genes might serve as predictive biomarkers of the TNBC treatment response.

Prognostic value of molecular subtypes, ki67 expression and impact of postmastectomy radiation therapy in breast cancer patients with negative lymph nodes after mastectomy.

PURPOSE: To determine whether Ki67 expression and breast cancer subtypes could predict locoregional recurrence (LRR) and influence the postmastectomy radiotherapy (PMRT) decision in breast cancer (BC) patients with pathologic negative lymph nodes (pN0) after modified radical mastectomy (MRM). METHODS AND MATERIALS: A total of 699 BC patients with pN0 status after MRM, treated between 2001 and 2008, were identified from a prospective database in a single institution. Tumors were classified by intrinsic molecular subtype as luminal A or B, HER2+, and triple-negative (TN) using estrogen, progesterone, and HER2 receptors. Multivariate Cox analysis was used to determine the risk of LRR associated with intrinsic subtypes and Ki67 expression, adjusting for known prognostic factors. RESULTS: At a median follow-up of 56 months, 17 patients developed LRR. Five-year LRR-free survival and overall survival in the entire population were 97%, and 94.7%, respectively, with no difference between the PMRT (n=191) and no-PMRT (n=508) subgroups. No constructed subtype was associated with an increased risk of LRR. Ki67 >20% was the only independent prognostic factor associated with increased LRR (hazard ratio, 4.18; 95% CI, 1.11-15.77; P<.0215). However, PMRT was not associated with better locoregional control in patients with proliferative tumors. CONCLUSIONS: Ki67 expression but not molecular subtypes are predictors of locoregional recurrence in breast cancer patients with negative lymph nodes after MRM. The benefit of adjuvant RT in patients with proliferative tumors should be further investigated in prospective studies.

Radiotherapy for stage II and stage III breast cancer patients with negative lymph nodes after preoperative chemotherapy and mastectomy.

PURPOSE: To evaluate the effect of postmastectomy radiotherapy (PMRT) in Stage II-III breast cancer patients with negative lymph nodes (pN0) after neoadjuvant chemotherapy (NAC). PATIENTS AND MATERIALS: Of 1,054 breast cancer patients treated with NAC at our institution between 1990 and 2004, 134 had pN0 status after NAC and mastectomy. The demographic data, tumor characteristics, metastatic sites, and treatments were prospectively recorded. The effect of PMRT on locoregional recurrence-free survival and overall survival (OS) was evaluated by multivariate analysis, including known prognostic factors. RESULTS: Of the 134 eligible patients, 78 (58.2%) received PMRT and 56 (41.8%) did not. At a median follow-up time of 91.4 months, the 5-year locoregional recurrence-free survival and OS rate was 96.2% and 88.3% with PMRT and 92.5% and 94.3% without PMRT, respectively (p = NS). The corresponding values at 10 years were 96.2% and 77.2% with PMRT and 86.8% and 87.7% without PMRT (p = NS). On multivariate analysis, PMRT had no effect on either locoregional recurrence-free survival (hazard ratio, 0.37; 95% confidence interval, 0.09-1.61; p = .18) or OS (hazard ratio, 2.06; 95% confidence interval, 0.71-6; p = .18). This remained true in the subgroups of patients with clinical Stage II or Stage III disease at diagnosis. A trend was seen toward poorer OS among patients who had not had a pathologic complete in-breast tumor response after NAC (hazard ratio, 6.65; 95% confidence interval, 0.82-54.12; p = .076). CONCLUSIONS: The results from the present retrospective study showed no increase in the risk of distant metastasis, locoregional recurrence, or death when PMRT was omitted in breast cancer patients with pN0 status after NAC and mastectomy. Whether the omission of PMRT is acceptable for these patients should be addressed prospectively.

Locoregional treatment for breast carcinoma after Hodgkin's lymphoma: the breast conservation option.

PURPOSE: To report clinical and pathologic characteristics and outcome of breast cancer (BC) after irradiation for Hodgkin's lymphoma (HL) in women treated at the Institut Curie, with a special focus on the breast-conserving option. METHODS AND MATERIALS: Medical records of 72 women who developed either ductal carcinoma in situ or Stage I-III invasive carcinoma of the breast after HL between 1978 and 2009 were retrospectively reviewed. RESULTS: Median age at HL diagnosis was 23 years (range, 14-53 years). Median total dose received by the mediastinum was 40 Gy, mostly by a mantle-field technique. Breast cancers occurred after a median interval of 21 years (range, 5-40 years). Ductal invasive carcinoma and ductal carcinoma in situ represented, respectively, 51 cases (71%) and 14 cases (19%). Invasive BCs consisted of 47 cT0-2 tumors (82%), 5 cN1-3 tumors (9%), and 20 Grade 3 tumors (35%). Locoregional treatment for BCs consisted of mastectomy with (3) or without (36) radiotherapy in 39 patients and lumpectomy with (30) or without (2) adjuvant radiotherapy in 32 patients. The isocentric lateral decubitus radiation technique was used in 17 patients after breast-conserving surgery (57%). With a median follow-up of 7 years, 5-year overall survival rate and locoregional control rate were, respectively, 74.5% (95% confidence interval [CI], 64-88%) and 82% (95% CI, 72-93%) for invasive carcinoma and 100% (95% CI, 100 -100%) and 92% (95% CI, 79-100%) for in situ carcinoma. In patients with invasive tumors, the 5-year distant disease-free survival rate was 79% (95% CI, 69-91%), and 13 patients died of progressive BC. Contralateral BC was diagnosed in 10 patients (14%). CONCLUSIONS: Breast-conserving treatment can be an option for BCs that occur after HL, despite prior thoracic irradiation. It should consist of lumpectomy and adjuvant breast radiotherapy with use of adequate techniques, such as the lateral decubitus isocentric position, to protect the underlying heart and lung.

Brain metastases from breast cancer: proposition of new prognostic score including molecular subtypes and treatment.

To develop a specific prognostic score for patients with brain metastases (BM) from breast cancer (BC), including the BC molecular subtype and treatment parameters, we analyzed the outcome of 130 patients with BM from BC who received whole-brain radiotherapy. We identified hierarchical risk groups for estimated survival by using recursive partitioning analysis (RPA). Seven prognostic factors, namely performance status, age, trastuzumab-based therapy for HER-2-overexpressing tumors, a triple-negative phenotype, Scarff-Bloom-Richardson grade, the serum LDH level and the lymphocyte count at BM diagnosis, were incorporated in the RPA. The final RPA nodes were grouped according to the survival time. The RPA tree showed that survival was best (median 19.5 months) among patients with HER2-overexpressing tumors who received trastuzumab-based therapy. The worst survival (median 3.5 months) was observed among patients who did not receive trastuzumab and who had lymphopenia at BM diagnosis, or KPS <70 and age over 50 years, or KPS ≥70 and a triple-negative tumor (HR- & HER-2-). The other patients had a median survival of 12.5 months (P < 0.001). This 3-class specific prognostic score successfully predicted the outcomes of a heterogeneous group of patients with brain metastases from BC.

Brain metastases from breast cancer: prognostic significance of HER-2 overexpression, effect of trastuzumab and cause of death.

BACKGROUND: To access the prognostic significance of HER-2 overexpression, the effect of trastuzumab and the cause of death in patients with brain metastases (BM) from breast cancer (BC). METHODS: We analyzed the outcome of 130 patients with BM from BC who received whole-brain radiotherapy (WBRT) (without surgery or radiosurgery) between January 1998 and April 2006. Demographic data, tumor characteristics, and treatments were prospectively recorded. The impact of HER-2 overexpression and trastuzumab-based therapy on overall survival (OS) and the cause of death were evaluated. RESULTS: The median follow-up for the whole population was 6.25 months (mean: 9.15; range: 0.23-53). The median survival time and 1-year survival rates after BM diagnosis were 7.43 months and 35.8% (95% CI: 28-45.7) respectively. The median survival time for HER-2 negative patients (n = 78), HER-2 positive patients not treated with trastuzumab (n = 20) and HER-2 positive patients treated with trastuzumab (n = 32) were 5.9 months, 5.6 months and 19.53 months, respectively. The 1-year survival rates were 26.1%, 29.2% and 62.6% respectively, (p < 0.004). Among the 18 HER-2 positive patients treated with trastuzumab who died, 11 (61%) apparently succumbed from CNS progression, in the face of stable or responsive non-CNS disease. Trastuzumab-based therapy was associated with a 51% reduction in the risk of death (multiadjusted hazard ratio: 0.49; 95% CI, 0.29-0.83). CONCLUSIONS: In our experience, trastuzumab-based therapy for HER-overexpressing tumors was associated with improved survival in BM BC patients. This subgroup of patients may benefit from innovative approaches, in order to obtain better intra cerebral control.

[Brain metastases from breast cancer: usefulness and limits of prognostic scores]. / Métastases cérébrales des cancers du sein : intérêt et limites des scores pronostiques.

Approximately 10 to 30% of patients with metastatic breast cancer will develop brain metastases (BM) during the disease course. Whole-brain radiation therapy (WBRT) is considered the standard treatment for most patients, particularly those with extensive intracranial disease, providing symptom relief and increasing median and overall survival. Despite WBRT, the prognosis for the general population of patients with BM remains poor, with a median survival time of approximately five months. Several studies have examined the relative contributions of patient characteristics to survival and have attempted to identify subgroups of patients with substantially different outcomes in order to tailor therapy and to influence the design, stratification and interpretation of future clinical trials. This review examines prognostic scores and their validation in patients with BM from breast carcinoma. We also discuss the prognostic value of specific parameters for breast carcinoma, such as tumor HR status, HER2 over-expression or specific treatment parameters, and the value and limits of these prognostic scores in clinical practice.

[Leptomeningeal meningitis related to breast cancer overexpressing HER2: is there a place for a more specific treatment?]. / Méningites carcinomateuses des cancers du sein surexprimant HER2 : pour un traitement spécifique ?

Leptomeningeal metastases are very commonly associated with breast cancer. The prognosis is very poor in the short term with an overall median survival less than 6 months. Based on pragmatic and historical considerations intrathecal chemotherapy (IT) are considered to be the adequate treatment. However overall results are disappointing. Despite specific and symptomatic treatment, improvement in survival and quality of life remains very modest, highlighting the importance for ongoing research for developing new molecules or on improving the use a better use of those available today. The incidence of leptomeningeal metastases is particularly marked in cases of overexpression of HER2. The main hypothesis is there may be a better control of extra-cerebral localisations with trastuzumab therefore intra-cerebral recurrences may be encountered preferentially as they are not reached by this high molecular weight monoclonal antibody (148  kD). Analyses performed in the cerebrospinal fluid following intravenous trastuzumab showed extremely low levels of the antibody and support the hypothesis that leptomeningeal metastasis of HER2-overexpressing breast carcinoma remain potentially sensitive to HER2-type receptor inhibition by a target agent under the condition of by-passing the meningeal blood brain barrier. Intra-ventricular or IT administered with trastuzumab would reach high loco-regional therapeutic concentrations in the cerebro-meningeal without risk for normal non-expressing HER2 leptomeningeal tissue. This strategy has been successfully tested on several animal models. A limited number of administrations in humans have been described in the literature, with weekly doses up to 100  mg. No specific toxicity has been described and some data suggest a potential benefit in survival despite the real difficulties for adequate interpretations. Furthermore, a multicentric phase I-II clinical trial, of which the Curie institute is the sponsor and investigating the intra-thecal administration and the efficacy of the trastuzumab will begin very soon. More studies are needed to measure the exact impact of small molecule inhibitors of tyrosine kinase on the leptomeningeal localizations.

[Concurrent whole-brain radiotherapy with trastuzumab for treatment of brain metastases in breast cancer patients: questions and answers]. / Association concomitante d'une irradiation encéphalique en totalité avec trastuzumab concomitant pour des métastases cérébrales d'un cancer du sein : questions et réponses.

PURPOSE: We retrospectively assessed the use of trastuzumab concurrently with whole-brain radiotherapy (WBRT) for brain metastases. PATIENTS AND METHODS: From April 2001 to April 2007, 31 patients with brain metastases from HER2-positive breast cancer were referred for WBRT with concurrent trastuzumab. In most cases, concurrent WBRT delivered 30 Gy in 10 daily fractions. In six patients, other fractionations were chosen because of either poor performance status or patients' convenience. RESULTS: At time of brain progression, median age was 55 years (range: 38 to 73 years) and all patients had a performance status of 0 to 2. Median time to brain progression was 10.5 months. Following WBRT, radiological responses were observed in 23 patients (74.2%), including six patients (19.4%) with complete radiological responses and 17 patients (54.8%) with partial radiological response. Clinical responses were observed in 27 patients (87.1%). Median survival from the start of WBRT was 18 months (range: two to 65 months). No grade 2 or more acute toxicity was observed. CONCLUSION: Our results suggest that trastuzumab concurrently with WBRT may have a potential clinical impact with low toxicity. Although promising, these preliminary data warrant further validation of trastuzumab as radio sensitizer for WBRT in brain metastases from breast cancer in the setting of a clinical trial. Larger prospective studies are needed to confirm these results.

Exclusive and adjuvant radiotherapy in breast cancer patients with synchronous metastases.

BACKGROUND: Data from the Surveillance, Epidemiology, and End Results program and the European Concerted Action on survival and Care of Cancer Patients (EUROCARE) project indicate that about 6% of women newly diagnosed with breast cancer have stage IV disease, representing about 12 600 new cases per year in the United States in 2005. Historically, local therapy of the primary tumor in this setting has been aimed solely at symptom palliation. However, several studies suggest that surgical excision of the primary tumor can prolong these patients' survival. DISCUSSION: Exclusive locoregional radiotherapy is an alternative form of locoregional treatment in this setting and may represent an effective alternative to surgery in this setting. Here we discuss current issues regarding exclusive and adjuvant locoregional radiotherapy in breast cancer patients with synchronous metastases. SUMMARY: Several studies suggest that surgery or exclusive irradiation of the primary tumor is associated with better survival in breast cancer patients with synchronous metastases and that exclusive locoregional radiotherapy may represent an effective alternative to surgery in this setting. Results of well-designed prospective studies are needed to re-evaluate treatment of the primary breast tumor in patients with metastases at diagnosis, and to identify those patients who are most likely to benefit.

Is regional lymph node irradiation necessary in stage II to III breast cancer patients with negative pathologic node status after neoadjuvant chemotherapy?

PURPOSE: Neoadjuvant chemotherapy (NAC) generally induces significant changes in the pathologic extent of disease. This potential down-staging challenges the standard indications of adjuvant radiation therapy. We assessed the utility of lymph node irradiation (LNI) in breast cancer (BC) patients with pathologic N0 status (pN0) after NAC and breast-conserving surgery (BCS). METHODS AND MATERIALS: Among 1,054 BC patients treated with NAC in our institution between 1990 and 2004, 248 patients with clinical N0 or N1 to N2 lymph node status at diagnosis had pN0 status after NAC and BCS. Cox regression analysis was used to identify factors influencing locoregional recurrence-free survival (LRR-FS), disease-free survival (DFS), and overall survival (OS). RESULTS: All 248 patients underwent breast irradiation, and 158 patients (63.7%) also received LNI. With a median follow-up of 88 months, the 5-year LRR-FS and OS rates were respectively 89.4% and 88.7% with LNI and 86.2% and 92% without LNI (no significant difference). Survival was poorer among patients who did not have a pathologic complete primary tumor response (hazard ratio, 3.05; 95% confidence interval, 1.17-7.99) and in patients with N1 to N2 clinical status at diagnosis (hazard ratio = 2.24; 95% confidence interval, 1.15-4.36). LNI did not significantly affect survival. CONCLUSIONS: Relative to combined breast and local lymph node irradiation, isolated breast irradiation does not appear to be associated with a higher risk of locoregional relapse or death among cN0 to cN2 breast cancer patients with pN0 status after NAC. These results need to be confirmed in a prospective study.

DNA repair gene expression and risk of locoregional relapse in breast cancer patients.

PURPOSE: Radiation therapy appears to kill cells mainly by inducing DNA double-strand breaks. We investigated whether the DNA repair gene expression status might influence the risk of locoregional recurrence (LRR) in breast cancer patients. METHODS AND MATERIALS: We used a quantitative reverse transcriptase PCR-based approach to measure messenger RNA levels of 20 selected DNA repair genes in tumor samples from 97 breast cancer patients enrolled in a phase III trial (Centre René Huguenin cohort). Normalized mRNA levels were tested for an association with LRR-free survival (LRR-FS) and overall survival (OS). The findings were validated in comparison with those of an independent cohort (Netherlands Cancer Institute (NKI) cohort). Multivariate analysis encompassing known prognostic factors was used to assess the association between DNA repair gene expression and patient outcome. RESULTS: RAD51 was the only gene associated with LRR in both cohorts. With a median follow-up of 126 months in the CRH cohort, the 5-year LRR-FS and OS rates were 100% and 95% in the 61 patients with low RAD51 expression, compared with 70% and 69% in the 36 patients with high RAD51 expression, respectively (p < 0.001). RAD51 overexpression was associated with a higher risk of LRR (hazard ratio [HR], 12.83; 95% confidence interval [CI], 3.6-45.6) and death (HR, 4.10; 95% CI, 1.7-9.7). RAD51 overexpression was also significantly associated with shorter LRR-FS and OS in the NKI cohort. CONCLUSIONS: Overexpression of RAD51, a key component of the homologous DNA repair pathway, is associated with poor breast cancer outcome. This finding warrants prospective studies of RAD51 as a prognosticator and therapeutic target.

Breast cancer with synchronous metastases: survival impact of exclusive locoregional radiotherapy.

PURPOSE: Several studies suggest that surgical excision of the primary tumor improves survival among patients with stage IV breast cancer at diagnosis. Exclusive locoregional radiotherapy (LRR) is an alternative form of locoregional treatment (LRT) in this setting. We retrospectively studied the impact of LRT on the survival of breast cancer patients with synchronous metastases. PATIENTS AND METHODS: Among 18,753 breast cancer patients treated in our institution between 1980 and 2004, 598 patients (3.2%) had synchronous metastasis at diagnosis. Demographic data, tumor characteristics, metastatic sites, and treatments were prospectively recorded. The impact of LRT on overall survival (OS) was evaluated by multivariate analysis including known prognostic factors. RESULTS: Among 581 eligible patients, 320 received LRT (group A), and 261 received no LRT (group B). LRT consisted of exclusive LRR in 249 patients (78%), surgery of the primary tumor with adjuvant LRR in 41 patients (13%), and surgery alone in 30 patients (9%). With a median follow-up time of 39 months, the 3-year OS rates were 43.4% and 26.7% in group A and group B (P =.00002), respectively. The association between LRT and improved survival was particularly marked in women with visceral metastases. LRT was an independent prognostic factor in multivariate analysis (hazard ratio [HR] = 0.70; 95% CI, 0.58 to 0.85; P = .0002). The adjusted HR for late death (>or= 1 year) was 0.76 (95% CI, 0.61 to 0.96; P = .02). CONCLUSION: In our experience, LRT, consisting mainly of exclusive LRR, was associated with improved survival in breast cancer patients with synchronous metastases. Exclusive LRR may thus represent an active alternative to surgery.

Histopathological response to preoperative chemoradiation for resectable pancreatic adenocarcinoma: the French Phase II FFCD 9704-SFRO Trial.

PURPOSE: This study suggests that pancreatic adenocarcinoma is a chemoradiosensitive tumor and that preoperative chemoradiation provides antitumoral effect associated with major histopathological response in 50% of patients and a high R0 resection rate. Evaluation of histopathological response to neoadjuvant therapy may serve as a surrogate marker for treatment efficacy and remains an active area of investigation. OBJECTIVES: The chemoradiosensitive of pancreatic adenocarcinoma has not yet fully been assessed. The purpose of this study is to determine the efficacy of preoperative chemoradiation, measured by the impact on the R0 resection rate and the histopathological response rate in patients presenting with resectable pancreatic adenocarcinoma. METHODS: Patients with localized, potentially resectable pancreatic adenocarcinoma were treated with 50 Gy irradiation combined with 5-fluorouracil by continuous infusion (300 mg . m(-2) . d(-1); day 1-5; week 1-5) and cisplatin (20 mg . m(-2) . d(-1); day 1-5 and day 29-33). Patients presenting with resectable disease at restaging, without metastatic dissemination, underwent surgical resection. RESULTS: Forty-one patients were enrolled. Twenty-seven patients (67.5%) completed chemoradiation receiving at least 75% prescribed chemotherapy dose without grade 4 nonhematological toxicity. Twenty-six patients (63%) underwent surgical resection with curative intent and 21 (80.7%) had R0 resection. Thirteen of 26 specimens (50%) presented a major pathologic response with more than 80% of severely degenerative cancer cells. Complete pathologic response was observed in one specimen. Median survival time and 2-year survival rate were 9.4 months and 20% for the entire cohort. The local recurrence and 2-year survival rates were 4% and 32%, respectively, for the 26 operated patients. CONCLUSIONS: This study suggests that some pancreatic adenocarcinomas are chemoradiosensitive and that preoperative chemoradiation provides antitumoral effect associated with major histopathological response in 50% of patients and a high R0 resection rate. Further research is needed to determine the biologic difference between responders and nonresponders, to evaluate the predictive value of treatment response parameters, and to optimize the chemoradiation regimen.

Brain metastases from breast carcinoma: validation of the radiation therapy oncology group recursive partitioning analysis classification and proposition of a new prognostic score.

PURPOSE: To validate the Radiation Therapy Oncology Group Recursive Partitioning Analysis (RTOG RPA) classification and determine independent prognostic factors, to create a simple and specific prognostic score for patients with brain metastases (BM) from breast carcinoma treated with whole-brain radiotherapy (WBRT). METHODS AND MATERIALS: From January 1998 through December 2003, 132 patients with BM from breast carcinoma were treated with WBRT. We analyzed several potential predictors of survival after WBRT: age, Karnofsky performance status, RTOG-RPA class, number of BM, presence and site of other systemic metastases, interval between primary tumor and BM, tumor hormone receptor (HR) status, lymphocyte count, and HER-2 overexpression. RESULTS: A total of 117 patients received exclusive WBRT and were analyzed. Median survival with BM was 5 months. One-year and 2-year survival rates were 27.6% (95% confidence interval [CI] 19.9-36.8%) and 12% (95% CI 6.5-21.2%), respectively. In multivariate analysis, RTOG RPA Class III, lymphopenia (< or =0.7 x 10(9)/L) and HR negative status were independent prognostic factors for poor survival. We constructed a three-factor prognostic scoring system that predicts 6-month and 1-year rates of overall survival in the range of 76.1-29.5% (p = 0.00033) and 60.9-15.9% (p = 0.0011), respectively, with median survival of 15 months, 5 months, or 3 months for patients with none, one, or more than one adverse prognostic factor(s), respectively. CONCLUSIONS: This study confirms the prognostic value of the RTOG RPA classification, lymphopenia, and tumor HR status, which can be used to form a prognostic score for patients with BM from breast carcinoma.

UV-light induced radiation recall dermatitis after a chemoradiotherapy organ preservation protocol.

This case report documents a UV-light-induced recall phenomenon and reviews the medical literature. In this patient, we observed a severe recall phenomenon precipitated by an extensive sunlight exposure after a chemoradiotherapy organ preservation protocol. Radiation recall phenomenon is a rare but well-described phenomenon, without clear radiation or drug-specific characteristics. In the medical literature, radiation recall following UV-sunlight exposure seems to be an exceptional event. The etiology remains unknown but could involve local hypersensitivity through a non-immune activation of inflammatory pathways. Due to the increasing number of patients with head and neck malignancies managed with induction chemotherapy and/or chemoradiation organ preservation protocols, the otorhinolaryngologist--head and neck surgeons as well as the radiation therapist should become aware and familiar with this phenomenon.

[Adjuvant and neoadjuvant treatment for pancreatic adenocarcinoma in 2006]. / Traitement adjuvant et néoadjuvant des adénocarcinomes pancréatiques en 2006.

About 5,300 new cases of pancreatic adenocarcinomas are diagnosed each year in France. At the time of diagnosis, an efficient carcinologic surgery will not be possible for nearly 80% of patients, in relation to locoregional extension or metastatic dissemination. After surgical resection, the median survival of resected patients ranges from 12 to 20 months, with a high rate of loco-regional or metastatic relapses. Numerous therapeutic trials, adjuvant or neo-adjuvant, have been conducted in aim of which to improve locoregioanl control and survival rates. Chemotherapy and chemoradiotherapy represent adjuvant treatments. In one trial, a chemotherapy regimen with 5-fluorouracil and folinic acid (FUFOL) has proven its efficience for survival improvement by comparison to chemoradiotherapy and is at this time the reference treatment in Europe. In another trial, using adjuvant gemcitabine results in an improvement in disease-free survival. Some phase III trials are in progress to evaluate new therapeutic strategies. The aim of neoadjuvant strategy using chemoradiotherapy is to enhance the rate of complete resections and by the way local control. This is under evaluation. This paper presents a summary of adjuvant and neoadjuvant trials for patients with potentially resectable pancreatic adenocarcinoma.