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Current events in radiotherapy oncology are marked by the results of strategic trials, particularly for esophageal and rectal cancers. For resectable esophageal adenocarcinoma, results of the ESOPEC study showed a benefit in overall survival from the perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin and docetaxel compared to chemoradiotherapy (41.4Gy radiotherapy and carboplatin/paclitaxel chemotherapy). In definitive setting, the CONCORDE study did not show any benefit from dose escalation and the standard dose remains 50Gy. For resectable pancreatic cancer, the NRG/RTOG0848 study that compared adjuvant chemotherapy with or without chemoradiotherapy found a significant increase of the 5-year disease-free survival rate in the subgroup of node-negative patients. For rectal cancers, the 7-year update of PRODIGE 23 study confirmed the benefit in disease-free- and overall survival of neoadjuvant folinic acid, fluorouracil, irinotecan and oxaliplatin chemotherapy before chemoradiotherapy of T3, T4 or N+ adenocarcinoma, while the update of the RAPIDO study revealed an unacceptable local recurrence rate in the experimental arm. The update of the OPRA study shows a significantly higher 5-year organ preservation rate in favor of the chemoradiotherapy arm followed by consolidation chemotherapy compared to induction chemotherapy followed by CRT. A phase 2 study, including 41 patients with mismatch repair deficient, locally advanced rectal cancer reported that exclusive treatment with anti-PDL1 immunotherapy (dostarlimab) for 6 months resulted in complete clinical response without the need of additional treatment (neither radiotherapy nor surgery). For anal carcinoma, the analysis of survival and toxicity profiles of patients treated for a small stage T1 or T2 tumor were compared depending on whether they received exclusive radiotherapy or chemoradiotherapy. The addition of chemotherapy to radiotherapy did not show any survival benefit but significantly increased toxicity and the risk of radiotherapy disruption., (Copyright © 2024. Published by Elsevier Masson SAS.)

Pancreatic cancer has poor prognosis and a continuously growing incidence. By 2030, it should become the second cause of death by cancer worldwide and in France. The only curative treatment is surgery that is achievable in only 20% of patients at the time of initial diagnosis, with a high rate of incomplete resection. Neoadjuvant treatments using chemotherapy with or without radiotherapy are more often admitted to play an important role by selecting non-progressing cases who will benefit from surgery, by increasing the number of complete resection, and by making locally advanced and borderline tumours accessible to resection. However, the role of radiotherapy is still debated. Because of its dosimetric advantages, its short total duration, and its good tolerance with reduced volumes of irradiation, stereotactic radiotherapy has been largely studied. Compared to chemoradiotherapy, this technique could improve the therapeutic index helping to preserve the general status of patients in order to give them access to secondary surgery. It remains a promising technique still under evaluation, to be delivered ideally, as part of a clinical trial, or within an experimented team., (Copyright © 2021 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Stereotactic body radiation therapy (SBRT) for locally advanced pancreatic cancer (LAPC) is an emerging treatment option. Most studies showed local control of approximately 75% with no evidence of improved overall survival. Gastrointestinal toxicities could be significant, ranging up to 22% for acute toxicities≥grade 3+ and 44% for late toxicities≥grade 3+. Currently, no standardized guidelines for treatment and management scheme. We conducted a systemic review of published prospective and retrospective trials to evaluate the efficacy, safety, technical data, and discuss future directions., (Copyright © 2021 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Due to high dose gradients, stereotactic body radiation therapy requires high precision in the location of the tumour. Uncertainties in the positioning can introduce serious damage on organs at risk and consequently can reduce tumour local control. A better tumour location can be achieved by controlling its position with an efficient inter and intrafraction imaging procedure. The various imaging techniques available on treatment systems are presented and performances are discussed. Finally, propositions are given in terms of imaging system according to the location treated by stereotactic body radiation therapy., (Copyright © 2019 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

At diagnosis, about 15% of patients with pancreatic cancer present with a resectable tumour, 50% have a metastatic tumour, and 25% a locally advanced tumor (non-metastatic but unresectable due to vascular invasion) or borderline resectable. Despite the technical progress made in the field of radiation therapy and the improvement of the efficacy of chemotherapy, the prognosis of these patients remains very poor. Recently, the role of radiation therapy in the management of pancreatic cancer has been much debated. This review aims to evaluate the role of radiation therapy for these patients., (Copyright © 2018 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Currently, the use of radiation therapy for patients with pancreatic cancer is subject to discussion. In adjuvant setting, the standard treatment is 6 months of chemotherapy with gemcitabine and capecitabine. Chemoradiation (CRT) may improve the survival of patients with incompletely resected tumors (R1). This should be confirmed by a prospective trial. Neoadjuvant CRT is a promising treatment especially for patients with borderline resectable tumors. For patients with locally advanced tumors, there is no a standard. An induction chemotherapy followed by CRT for non-progressive patients reduces the rate of local relapse. Whereas in the first trials of CRT large fields were used, the treated volumes have been reduced to improve tolerance. Tumor movements induced by breathing should be taken in account. Intensity modulated radiation therapy allows a reduction of doses to the organs at risk. Whereas widely used, this technique is not recommended., (Copyright © 2016 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Pancreatic carcinoma is the fifth leading cause of cancer-related mortality. The 5-year overall survival is less than 5 %. This very poor prognosis can be explained both by late diagnosis and by treatment resistance, including resistance to radiation therapy. A better understanding of the pancreatic tumorigenesis and knowledge of the most frequent mutations in pancreatic adenocarcinoma (KRAS, p16, TP53, Smad4) open new perspectives for the development of more effective treatments. This review presents the major genetic and molecular alterations in pancreatic cancer that could be targeted to improve radiosensitization., (Copyright © 2011 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Purpose: To compare chemoradiation with systemic chemotherapy to chemotherapy alone in locally advanced pancreatic cancer., Patients and Methods: One hundred and nineteen patients with locally advanced pancreatic cancer, with World Health Organization performance status of zero to two were randomly assigned to either the induction chemoradiation group (60 Gy, 2 Gy/fraction; concomitant 5-fluoro-uracil infusion, 300 mg/m(2) per day, days 1-5 for 6 weeks; cisplatin, 20 mg/m(2) per day, days 1-5 during weeks 1 and 5) or the induction gemcitabine group (GEM: 1000 mg/m(2) weekly for 7 weeks). Maintenance gemcitabine (1000 mg/m(2) weekly, 3/4 weeks) was given in both arms until disease progression or toxicity., Results: Overall survival was shorter in the chemoradiation than in the gemcitabine arm (median survival 8.6 [99% confidence interval 7.1-11.4] and 13 months [8,9,9-18], p=0.03). One-year survival was, respectively, 32 and 53%. These results were confirmed in a per-protocol analysis for patients who received 75% or more of the planned dose of radiotherapy. More overall grades 3-4 toxic effects were recorded in the chemoradiation arm, both during induction (36 versus 22%) and maintenance (32 versus 18%)., Conclusion: This intensive induction schedule of chemoradiation was more toxic and less effective than gemcitabine alone., (Copyright © 2011. Published by Elsevier SAS.)

Purpose: Several phase II studies have shown the feasibility of neoadjuvant chemoradiation regimens for resectable localized pancreatic adenocarcinoma. However, there is to date no completed phase III study to validate this approach and treatment effects evaluation still remains an active area of investigation. From the mature results of the SFRO-FFCD 9704 trial, we explored the antitumoral effect of a 5-fluoro-uracil and cisplatin-based preoperative chemoradiation regimen, with a special highlight on the histopathological response and performed a literature review., Patients and Methods: Treatment consisted of concurrent radiotherapy (50 Gy within five weeks) and chemotherapy with 5-fluoro-uracil (300 mg/m(2)/day, five days/week, weeks 1-5) and cisplatin (20mg/m(2)/day, days 1-5 and 29-33), followed by surgical resection of the pancreatic tumour in patients without progression., Results: In all, 41 patients were enrolled, 26 patients (63%) underwent surgical resection with curative intent and 21 (80.7%) had R0 resection. A total of 13 of 26 specimens (50%) presented a major pathologic response (≥ 80% of severely degenerative cancer cells), with one complete pathologic response. The local recurrence and two-year survival rates were 4 and 32%, respectively, for the 26 operated patients., Conclusion: Our results suggest 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 chemoradiation may serve as a surrogate marker for treatment efficacy and further research is needed to determine new prognostic and predictive factors of treatment response., (Copyright © 2010 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

About 7200 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 loco-regional extension or metastatic dissemination. After surgical resection, the median survival of resected patients ranges from 12 to 20 months, with a high rate of relapses. Currently, the use of radiotherapy for patients with pancreatic cancer is controversial. In adjuvant setting, the standard treatment is six months of chemotherapy with FUFOL or gemcitabine. Chemoradiation (CRT) may improve the survival of patients with incompletely resected tumors (R1). This must be validated in a prospective trial. Neoadjuvant CRT is a promising treatment but always under evaluation. For the treatment of patients with locally advanced tumors, there is not a standart treatment. A strategy of initial chemotherapy followed by CRT for non progressive patients is under evaluation. Whereas in the first trials of CRT large fields were used, the current trend is to reduce the treated volumes to improve tolerance. The delineation of target volumes has been improved by the use of simulation CT. The aims of this work are to precise the radio-anatomical particularities, the pattern of spread of pancreatic cancer and the principles of 3D conformal radiotherapy illustrated with a clinical case., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

The management of gastroenteropancreatic endocrine tumors is greatly linked to the localization of primary tumor. Morphological imaging methods are thus necessary. However, the expression of somatostatin receptors in endocrine tumors makes their detection possible thanks to radiolabeled somastotatin analogs. [(111)In-DTPA] octreotide is the main radiolabeled analog for somatostatin receptor scintigraphy. Positron emission tomography uses other tracers and currently allows improvement of the diagnosis and the tumoral staging. It also allows to affect the therapeutic management. A further step is about to be taken as far as the therapy of endocrine tumors is concerned with the peptide receptor radionuclide therapy. Those therapies are now being offered in some European and American centers for progressive metastatic tumors. Their place in the therapeutic strategy has to be defined, especially in comparison to targeted therapy. The sudden and delayed adverse events as well as the current legislation on the use of radioactive therapy-aimed products have limited their development in France so far., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

About 7,200 new cases of pancreatic adenocarcinoma are diagnosed each year in France. At the time of diagnosis, only 20% of patients have an operable tumor; 30% have local or regional extensions and 50% metastatic dissemination. Median survival of patients after surgical resection ranges from 12 to 20 months, because of the high relapse rate. Currently, the use of radiotherapy is controversial for patients with operable or locally advanced pancreatic cancer. The standard treatment is six months of chemotherapy with FUFOL or gemcitabine. Combining it with radiation therapy as an adjuvant (CRT) may improve the survival of patients with incompletely resected tumors. This must still be demonstrated in a prospective trial. Neoadjuvant CRT is a promising treatment but still under evaluation. There is no standard treatment for patients with locally advanced tumors. A strategy of initial chemotherapy (gemcitabine) followed by CRT for patients with non-progressive tumors is under evaluation in the LAP07randomized trial., (Copyright 2009 Elsevier Masson SAS. All rights reserved.)

Since the first Japanese publications, intraoperative radiotherapy (IORT) has been used with electrons delivered with homogeneous techniques in miscellaneous indications. The main goal was to increase the total dose in a limited volume leading to an optimized therapeutic ratio between the tumor and the healthy tissue. The main indications are not only recurrences of digestive and gynecological tumors but also retroperitoneal sarcomas. Recently, the development of the concept of partial breast irradiation reinforces the use of such a technique in the strategy of breast-conserving surgery for small tumors in the elderly. IORT was evaluated either as boost or as an exclusive treatment delivering one fraction during the surgical procedure.

Introduction: At the request of the National Thesaurus of Gastrointestinal Cancer (TNCD), the SOR program undertaken by the French Federation of Cancer Centers (FNCLCC) and now led by the French National Cancer Institute (INCa), completed a systematic review to evaluate the value of chemoradiotherapy (CRT) in the management of locally advanced pancreatic adenocarcinoma in collaboration with clinician experts., Methods: Results of a systematic literature search using Medline (from 1980 to 2008) were completed by a consult of evidence-based medicine websites. All phase III randomized trials and systematic reviews concerning non resectable locally advanced pancreatic adenocarcinoma and non metastatic (stage III) were included in the study. Some phase II trials were also included if no phase III trials were retrieved. The following interventions were compared: CRT versus best supportive care (BSC), CRT versus radiotherapy, and CRT versus chemotherapy. The modalities of CRT regimens and the sequences of chemotherapy-CRT versus CRT were also studied. The quality and clinical relevance of the trials were evaluated using validated checklists, allowing associating each result with a level of evidence. Data synthesis was performed considering both efficacy and toxicity outcomes for each intervention., Results: Nineteen references were included in this systematic review: 2 meta-analyses, 11 randomized trials, 5 non-randomized trials and 1 randomized trial only published in abstract form. After a clinical and methodological critical appraisal, compared to the alternative BSC, concomitant CRT increases overall survival (C). Concomitant CRT compared to the radiotherapy alone increases the overall survival (B1) but is more toxic (B1). Concomitant CRT compared to chemotherapy alone is not superior in terms of survival (B1) and increases toxicity (A). Concerning administration modalities of radiotherapy, recent data are in favour to a limited irradiation to the tumoral volume (C) and to a total dose of 50-60 Gy in association with 5-FU. The study of radiotherapy associated drugs shows that 5-FU is the reference (B1) and the value of gemcitabine must be proved in randomized trials. Finally, the study of sequences chemotherapy-CRT has recently showed that induction chemotherapy before CRT improves survival (C). Validation of this strategy in a randomized trial is warranted., Conclusion: The use of CRT for locally advanced pancreatic adenocarcinoma is based on a few randomized trials even if this treatment appears superior in terms of survival compared to BSC and radiotherapy alone. This review shows the need to conduct other specific randomized trials in order to validate the value of CRT, especially compared to chemotherapy alone.

Objectives are to validate a simple classification for irradiated specimens and assessing the incidence and the outcome of sterilized forms. Between 1996 and 2005, 56 non metastatics patients had preoperative chemoradiation and curative resection for pancreatic adenocarcinoma. We retrospectively applied the Dworak regression scale previously describe for rectal cancer. Dworak 4 (sterilized tumor), 3, 2, 1 and 0 grades interested 7 (12,5%), 12, 12, 11 and 14 patients respectively. The median estimated overall survival of all patients was 24 months with estimated 1-, 3- and 5-year survivals of 80%, 35% and 18% respectively. Statistical analysis permitted to regroup patients classified Dworak 4 or 3 (grade 2 of our modified Dworak classification (MDC)) and Dworak 2, 1 or 0 (grade 1 of our MDC). Patients with grade 2 MDC had an estimated median survival and 5-years survival of 40 months and 28 % respectively. Eleven patients (58%) with grade 2 MDC (n = 19) had exclusive metastatic recurrences. Nineteen patients with grade 1 MDC (n = 37) had metastatic (n = 17 ; 46% ; p = 0,07) or local recurrences (n = 2). The MDC was useful because a) easy to used and b) correlated with good prognostic factor for patients with grade 2 MDC. However, metastatic recurrence rate didn't differed in the 2 groups. Thus, adenocarcinoma of the pancreas had to be treated by surgical curative resection associated with radiotherapy and systemic chemotherapy to control the both side, metastatic and local, of the disease. The best preoperative treatment had to be define but must include CRT and systemic chemotherapy.

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.

Although complete surgical resection, when possible, leads to prolonged survival in pancreatic cancer, if used alone, its results remain sub-optimal. Neoadjuvant strategies are recent in pancreatic cancer: in primary resectable tumors, they ensure that all patients obtain additional treatment to complete surgery; in locally advanced tumors, they allow a better selection of candidates for curative resection. By delaying surgery, neoadjuvant strategies modify the initial diagnostic process and the symptomatic treatment of pancreatic cancer. Several recent phase I-II studies have confirmed the feasibility and efficacy of the association of chemotherapy and radiotherapy, which is well-tolerated and is associated with better local control and survival. Due to the aggressiveness of pancreatic cancers, most recent cytotoxic agents should be associated with modern radiation techniques. Neoadjuvant chemoradiation is under evaluation in pancreatic cancers, and no randomized phase III trials comparing neoadjuvant and adjuvant therapeutic sequences has been reported. Moreover, radiological and pathological evaluations, not only at diagnosis, but also after preoperative chemoradiation, must be standardized to improve the selection of patients who will benefit from this multi-modal treatment.

Unlabelled: Induction chemoradiotherapy (CRT) may downstage locally advanced pancreatic tumors but secondary resections are unfrequent. However some responders' patients may benefit of a R0 resection., Patients and Methods: We report 18 resections among 29 locally advanced pancreatic cancers; 15 patients were treated with neoadjuvant 5-FU-cisplatin based (13) or taxotere based (2 patients) chemoradiotherapy (45 Gy), and 3 patients without histologically proven adenocarcinoma were resected without any preoperative treatment., Results: The morbidity rate was 28% and the mortality rate was 7%; one patient died after resection (5.5%) and one died after exploration (9%). The R0 resection rate was 50%. The median survival for the resected patients was not reached and the actuarial survival at 3 years was 59%. Two specimens showed no residual tumor and the two patients were alive at 15 and 46 months without recurrence; one specimen showed less than 10% viable tumoral cells and the patient was alive at 36 months without recurrence. A mesenteric infarction was the cause of a late death at 3 years in a disease free patient (radiation induced injury of the superior mesenteric artery). The median survival of the 11 non-resected patients was 21 months and the actuarial survival at 2 years was 0%. When the number of the resected patients (18) was reported to the entire cohort of the patients with locally advanced pancreatic cancer treated during the same period in our institution, the secondary resectability rate was 9%., Conclusion: Preoperative chemoradiotherapy identifies poor surgical candidates through observation and may enhance the margin status of patients undergoing secondary resection for locally advanced tumors. However it remains difficult to evaluate the results in the literature because of the variations in the definitions of resectability. The best therapeutic strategy remains to be defined, because the majority of patients ultimately succumb with distant metastatic disease.

Primary squamous cell carcinoma of the pancreas is a rare tumor. We report a case of a 49 years old patient with a metastatic squamous cell carcinoma of the pancreas. Histological diagnosis was established by echoguided biopsy of the liver. Due to that, we cannot be sure that this tumor was not adenosquamous with a metastatic component from only the squamous part of the lesion. Two types of chemotherapy have been performed. The first one was radiochemotherapy with an association of 5FU and cisplatinum. Gemcitabin was the second one. An objective response was obtained with gemcitabin and the patient's health improved. To our knowledge, this has never had been reported beforehand. However the prognosis of this cancer remains poor. Overall survival was 8 months.

Surgery is the only curative treatment of gastro-entero-pancreatic endocrine tumors. In inoperable or metastasized forms, therapeutic options are limited. The metabolic or systemic radiotherapy, using radiolabeled somatostatin analogs, constitutes a new therapeutic alternative, currently in development which requires the presence of high affinity somatostatin receptors on tumoral cells. Using (111)In-pentetreotide, the main result is a symptomatic effect. With new somatostatin analogs coupled to B- emitters, such as Octreother or (177)Lu-DOTA-Octreotate, 10 to 30% of objective tumoral responses are observed in progressive patients, unresponsive to conventional treatments. Such results are explained by the high affinity for somatostatin receptors and the large emission diameter of these radiolabeled compounds. Renal toxicity is limited by amino-acid infusion whereas changes in blood count are usually moderate and transient. Multicentric prospective studies are necessary to identify the predictive factors of tumoral response and toxicity. The prospects are related to the development of new radiopharmaceuticals, even more specific of somatostatin receptors sub-types and to the use of other peptide analogues whose applications will overflow the framework of endocrine tumours.

Surgery remains the cornerstone treatment for pancreatic adenocarcinoma. However, 5% to 20% of tumors only are regarded as resectable, and, among them, only few benefit from an histological complete resection, major survival parameter. These data explain the overall poor prognosis of this disease, with a respectively 20% and 5% 1- and 5-year survival rates. These results justify an adjuvant or neoadjuvant therapeutic approach, mainly based on concurrent chemoradiation, with and without surgery. This paper reviews the different therapeutic approaches of non metastatic pancreatic adenocarcinoma.

Gemcitabine is pyrimidine analog which has demonstrated antitumoral activity in a variety of solid tumors. Laboratory studies demonstrating that gemcitabine is a potent radiosensitizer led to a variety of trials combining radiation and gemcitabine. In the clinic, phase I-II studies are still trying to determine the optimal dose and schedule which could be use in daily clinical practice. This review summarizes the mechanisms of interaction between radiotherapy and gemcitabine and presents several therapeutic schemes for each tumor location.

Prognosis of pancreatic carcinoma remains poor, with one-year and five-year overall survival rates of 20 and 5% respectively. Only 5 to 15% of patients present with tumors amenable to resection. Long-term (5 years) survival after curative resection is less than 20%, and the median survival is about 12 months. This paper updates recent trends about concomitant chemoradiation. At first, a review of the studies on adjuvant chemoradiation after surgery is proposed. Then, indications of preoperative chemoradiation for patients with localized resectable adenocarcinoma are discussed. The last part concerns the most important and recent studies about chemoradiation in locally advanced pancreatic cancer, either with 5-fluoro-uracile or based on new drugs like gemcitabine.

Gemcitabine is a molecule presenting with major radiosensitizing or radio-potentiator capacities. This property has been extensively studied in vitro, with clinical therapeutic implications. Chemotherapy and radiation are very often used together, most of the time concurrently. This review analyses the results obtained with combined gemcitabine and radiation, for non small cell lung cancer, pancreatic adenocarcinoma, head and neck and uterine cervix carcinomas. Several therapeutic schemes are presented, for each tumor location. A description of the toxicities observed is presented, including the recall phenomenon description. Promising results justify the numerous current trials, as well as enthusiasm initiated by this therapeutic association.

Introduction: Granulocyte sarcoma (GS), also known as chloroma, is a localized malignant tumor composed of myeloid cells, the diagnosis of which is difficult. The pancreatic location and recurrence, aside from any context of malignant hemopathy, are exceptional., Observation: A 31-year-old woman developed an isolated and recurrent granulocyte sarcoma of the pancreas, without any context of a malignant hemopathy. The diagnosis retained on extemporaneous examination was an adenocarcinoma of the pancreas, because of the non-specific necrotic nature of the tumor. The immuno-histochemical exploration corrected the diagnosis. Despite local surgery, an isolated tumor recurred 6 months later. This relapse was treated with radiotherapy followed by heavy chemotherapy, identical to that applied in acute myeloblastic leukemia (AML). Ten months later, remission was stable and complete., Comments: Isolated granulocyte sarcomas located in the pancreas are exceptional and have often led to initial erroneous diagnosis. Immuno-histochemical methods are essential in order to obtain correct diagnosis. Despite the localized nature of the tumor, intensive AML-type chemotherapy is necessary.

The prognosis of pancreatic adenocarcinoma remains poor, with a 5-year survival rate lower than 5%. Resection, the gold standard treatment, can be performed in less than 15% of patients. Following surgery, the median survival is 12 months for the most favourable cancer patients. Adjuvant treatment have attempted to improve results. However, chemotherapy, radiotherapy and multimodal treatments don't have demonstrated a clear advantage in controlled trials. We will discuss results of the current trials in this topic. The randomised trial of the European Study Group for Pancreatic Cancer (ESPAC) recently published in the Lancet revealed a potential benefit of adjuvant chemotherapy. A critical analysis of the publication showed, however, that definitive conclusions of this trial must be interpreted with caution.

Anatomical data of pancreas, biliary tree, regional lymph nodes is required to define GTV and CTV. In case of postoperative irradiation, CTV is designed in collaboration with radiation oncologist and surgeon oncologist. For exclusive radiotherapy, endodigestive ultrasonography, CT scan and MRI could help radiation oncologist defining GTV. Although, accuracy of all the imaging techniques in past years remains poor. Currently, no available literature is published regarding security margins for the definition of CTV. Therefore, recommendations according to clinical experience are proposed.

All the retrospective and prospective studies concerning IORT in tumors of the digestive tract tend to substantiate a significant improvement in local control without a significant increase in survival. Improvements in the results of IORT can be expected in the near future, and may occur on several fronts: - Technological improvements: advances in the development of IORT machines, with the construction of electron accelerators specifically designed for IORT; greater precision in the systems of collimation (asymmetric collimator, multiple leaves, computerization of the control of collimation); and increased adaptability of the localizers to each clinical situation and to each patients. - Increase in the biological effects of IORT: determination of the exact role of IORT in relation to other therapeutic methods, its integration into the global therapeutic strategy for cancer, and the optimization of IORT doses should all be studied in phase II and III trials. Interesting results are expected from the combination of different methods of preoperative, intraoperative, and postoperative radiotherapy with chemotherapy; the cumulative effect of radiosensitization and cytotoxicity can bring about both local control and treatment of the general disease. In addition, the combination of hypoxic cell radiosensitizers and IORT, a source of important cellular hypoxia as a result of single doses, appears promising. - Lastly, randomized studies in a larger number of patients with objectives and methodologies to be perfected will document the actual contribution of IORT to an increase in survival as part of an overall treatment strategy for digestive tumors. At present, the prognosis remains significantly related to systemic metastatic evolution; this can only be influenced by chemotherapy, whose efficacy remains to be demonstrated. As means for better control of systemic disease are discovered, the clear benefits of local control via IORT will assume increased importance.

Pancreatic tumors have a very bad prognosis even after complete surgery. Radiotherapy has an important role to play either postoperative with associated chemotherapy or palliative and alone. Presently 5-FU is the most widely used molecule but gemcitabine is getting more and more acceptance. Intraoperative radiotherapy but especially preoperative radiotherapy seem to be two promising techniques.

The prognosis of pancreatic adenocarcinoma remains poor, with a 5-year survival rate lower than 5%. Resection, the gold standard treatment, can be performed in less than 10% of patients. Following surgery, the median survival is 12 months. Concomitant chemoradiation, as an adjuvant treatment could be superior to surgery alone, in terms of survival; controlled trials are currently performed. Neoadjuvant chemoradiation is a new approach, potentially able to increase survival and resection rate. Finally, current data regarding intraoperative irradiation are exposed.

The last of the therapeutic modalities proposed for exocrine adenocarcinoma of the pancreas which appears to be potentially resectable, neoadjuvant chemoradiotherapy has many prerequisites: validation of the diagnosis, determination of resectability with a high degree of confidence and palliation of biliary obstruction when present. This rather complex strategy does not seem to have major deleterious effects on the operative procedure or the postoperative course. Only multicentric protocols will, in the near future, give an answer to the question of secondary toxic effects and improvement of survival of this new therapeutic strategy.

The prognosis of pancreatic adenocarcinoma remains poor, with a 5-year survival rate lower than 5%. Resection, the gold standard treatment, can be performed in less than 10% of patients. Following surgery, the median survival is 12 months for the most favorable cancer patients. Concomitant chemoradiation, as an adjuvant treatment is superior to surgery alone, in terms of survival; controlled trials are currently performed. Neoadjuvant chemoradiation is a new approach, potentially able to increase survival and resection rate. This work justifies the role of these schemes, in terms of modalities and potential advantages. A second part is dedicated to gastric carcinoma, with a review of the current results of chemoradiation, whose efficiency, even though a trend can be observed, remains to be proven. Prospective adjuvant combined treatments are ongoing, in France and in the States.

Purpose of the Study: Pre-operative radiochemotherapy is the most recent therapeutic option in the pre-operative downstaging of pancreatic cancer and in decreasing the rate of positive resection margins. The purpose of the study was to evaluate tolerance and efficacy of pre-operative radiochemotherapy in unresectable pancreatic cancers., Material and Methods: This study included seven cases of pancreatic cancer considered unresectable. The patients received preoperatively 50 grays within a 5-week period associated with 5 FU and Platin during the 1st and 5th weeks., Results: After radiochemotherapy, tomodensitometric evaluation showed a minor response in two cases. A pancreatico-duodenectomy could be performed in these two patients without any increase of pre- or post-operative morbidity or mortality., Conclusions: The results of the study suggest that preoperative radiochemotherapy may increase pancreatic cancer resectability. This hypothesis should be confirmed by a prospective randomised trial.

Surgery: Surgery whether curative or palliative, is the major modality of treatment. A complete resection is possible in about 20% of patients with a median survival of 12 to 16 months and a 20% five year survival. After complete resection 70 to 80% of patients develop a local recurrence. Biliary and gastro-intestinal bypasses as well as antalgic techniques are useful palliative procedures., Adjuvant and Neoadjuvant Treatment: Chemoradiotherapy is used either as adjuvant or neoadjuvant treatment. External beam irradiation techniques are used to deliver 45 to 50 Gy to the pancreas in five to six weeks. Concomitant fluorouracil is administered in bolus injections or better in continuous infusion,, either alone or in association with cisplatinum. Chemoradiotherapy reduces the local relapse rate and slightly, though significantly, increases the median survival. Therefore, after chemoradiotherapy, metastatic spread becomes the major cause of death., Palliative Treatment: For locally advanced diseases, chemoradiotherapy has a true palliative effect with acceptable toxicity. Metastatic disease remains a challenge. Fluorouracil based chemotherapy with or without cisplatinum occasionally obtains effective palliation. Among new agents, only gemcitabine has proven clinical activity associated with low toxicity and is practical to use., Therapeutic Strategy: Presently, patients with resectable pancreatic carcinoma should be included in a prospective trial to receive combined modality treatment with adjuvant or neo-adjuvant chemoradiotherapy. The choice of treatment for patients with locally advanced or metastatic disease, should be based on the possibility of assuring a satisfactory quality of life. Present research should progress through controlled clinical trials to study original systemic treatment and combined modalities able to produce a lasting local control.

Pancreatic cancer is a disease difficult to treat. Diagnosis is late, cancer remaining clinically unapparent even if locally advanced or metastatic. Few patients can be submitted to curative surgery. Even if resection is possible, 5-year survival varies from 0% to 18% according to series. Some data suggest that chemotherapy with or without radiotherapy could influence disease free survival but a benefit on overall survival has not been demonstrated. For locally advanced disease, the results of a trial published in 1968, showed that a combination of radiotherapy and 5-Fluorouracil (5FU) improved median survival as compared to radiotherapy alone (5.5 versus 10 months). Since then, no progress has been achieved. At the present time, survival of patients with metastatic pancreatic cancer cannot be improved. Very recently, a new agent, gemcitabine, has been compared to 5FU. Criteria for activity were based on clinical improvement analgesia consumption, performance status and weight gain. Twenty-four percent of the patients treated with gemcitabine had a clinical benefit as compared to 5% for those treated with 5FU. Other studies comparing chemotherapy to best supportive care show a significant decrease of depression and anxiety as well as an improvement in quality of life for patients being treated.

The aim of this study was to evaluate intraoperative radiotherapy in exocrine pancreatic cancer (n = 10) and in recurrent colorectal carcinoma (n = 11). Radiotherapy was delivered with electron beams (energy from 9 MeV to 20 MeV). Doses ranged from 15 Gy to 25 Gy. All patients with pancreatic cancer also received 40 Gy external beam irradiation and 5-Fluorouracil (500 mg/m2) and eight patients with recurrent colorectal carcinoma received postoperative external beam irradiation (20 Gy to 60 Gy). There were no postoperative deaths or complication. In pancreatic cancers, pain relief (7 cases) until death was observed in all cases. After palliative procedures (9 cases), the median survival time was 6 months (ranging from 4 months to 14 months). One patient is alive with a follow-up of 5 years and 6 months following total pancreatectomy. 5 patients with recurrent colorectal carcinoma, died with a median survival time of 13 months (ranging from 2 months to 25 months), and six patients are alive. Two of them have recurrence, and four are free of recurrence with a mean follow-up of 21 months (ranging from 3 months to 54 months). In conclusion, our results for pancreatic cancer agree with the disappointing results reported by other institutions. On the other hand, recurrence of colorectal carcinoma seems to be a good indication for intra-operative radiotherapy even when resection is incomplete.

A review of the literature over the last five years reveals that the results of treatment of pancreatic carcinoma have barely improved over the last thirty years, except in terms of the operative mortality which has markedly improved over the last decade. Pancreatectomy still constitutes the only, although slight, chance of cure. It must be reserved to the rare macroscopically curable cases, i.e. small tumours of the head of the pancreas, apparently confined to the pancreas. Palliative treatments should preferably be surgical. Endoscopic biliary drainage should only be performed in inoperable cases. Adjuvant radiotherapy and chemotherapy must be integrated into curative and palliative strategies. These various therapeutic modalities can only be evaluated by means of prospective studies and controlled trials.

Causes of relapse are related to diagnostic delay, disagreement between early clinical diagnosis and post-surgical classification, poor performance status of patients, biological features, treatment modalities and particularly subclinical disease left after radical surgery. Gastro-intestinal specialists, radiologists, surgeons, pathologists, radiation and medical oncologists must come together to propose the best strategy: exactness of pre- and post-operative staging; surgical resection performed with minimal and acceptable morbidity after due consideration of all associated risk factors; accurate pathological examination with mention of tumoral diameter, capsular invasion, multicentricity, lymph nodes and venous involvement, pTNM classification; precise systematic external beam radiotherapy, which may be enhanced by 5-FU.

Non-resectable pancreatic adenocarcinomas (PA) are of poor prognosis with median survival of 4-6 months. Radiotherapy (RT) and chemotherapy (CT) association are potential palliative treatments recently investigated. We have tested such an association in a pilot study. Twelve patients (pts) with non-resectable PA and localized tumors were treated by 2 cycles of CT (5-FU + adriamycin + cisplatinum) and then 2 or 3 split courses of RT (20 Gy/12 days and 8 fractions with a 16 day interval). CT was reintroduced, if initially active, for 3 cycles. Results were: 3 CR (11+, 13+, 16 months) for a response rate of 25%, 1 MR (4 months) and 5 stabilizations longer than 6 months. The 1 year survival was 56 +/- 15% with no patient surviving longer than 2 years. Tolerance was acceptable for RT and toxicity with CT was digestive (grade II) for all pts, leucopenia grade III for 3 pts and thrombopenia grade II for 2 pts. Two pts experienced digestive hemorrhage for anastomatic ulceration, responsible for death in one case. This pilot study confirms the transient efficacy of RT + CT association for non-resectable PA. However, the toxicity and treatment duration lead us to recommend other studies of less toxic association before initiation of randomized trials.

Since November 1985, we performed Intra Operative Radiation Therapy in 53 cases, essentially in gastric cancer (20 patients) and in pancreatic cancer (22 patients). Mortality and morbidity were not increased by the use of Intra Operative Radiation Therapy. Our follow up is too short to get any valid conclusions about IORT in gastric cancer. However, for unresectable pancreatic cancer, we observed an improvement of the survey when patients were treated by "Surgery, IORT and External post operative radiotherapy". We also studied the relief of abdominal and back pain of unresectable pancreatic cancer: in our experience, the survey was longer and more confortable for patients treated with surgery and IORT. In conclusion it appears that today IORT is surely a good palliative treatment for unresectable pancreatic cancer, and longer experience is needed to conclude for resectable pancreatic cancer and for gastric cancer.

Overall prognosis of pancreatic adenocarcinoma is still very poor with median survival around 10 months after radical surgery in operable patients, or after full-dose radiation therapy in non-surgical candidates. In metastatic disease, multidrug chemotherapy regimens give a response rate of around 30% with median survival of 10 months. Random trials conducted by the GITSG in inoperable cases have shown improved results for chemoradiation with 5-FU for radiotherapy alone and a doubling of median survival with a 1-year survival of 40% vs 10%. Incorporation of Adriamycin in these combined modality protocols does not improve the results in terms of survival. Chemoradiation also shows improved results compared with chemotherapy alone. In patients amenable to radical surgery, adjuvant post-operative treatment with chemoradiation gave superior results over surgery alone with a doubling of median survival and a significant improvement of a two-year survival rate (42% versus 15%). Intra-operative radiation therapy leads to better local control but without a significant improvement in survival. With a better understanding of radio-chemotherapy interactions and mechanisms of radiosensitization through continuous infusion of fluorouracil and/or cisplatinum, these encouraging results should be confirmed within the next few years.

Most pancreatic carcinomas are clinically observed when the tumoral spread is well advanced. Consequently, surgical excision is very often either partial or unfeasible. However, evolutive patterns of pancreatic carcinomas show a long past history of loco-regional spread before the onset of visceral metastasis. Consequently, radiotherapy could be proposed to treat locally advanced pancreatic tumors or residual disease after surgical excision in curative intend. The major challenge dealing with radiotherapeutic management of pancreatic carcinomas is to safely deliver doses as high as 60-70 Gy into the upper half of the abdominal cavity. Several technical conditions must be fulfilled before this can take place: high energy and multiple convergent photon beams, precise surgical and/or radiological description of tumoral extent, careful sparing of critical tissues such as spinal cord and kidneys. Usually, radiotherapeutic planning is administered in 2 successive sessions: 40-45 Gy are first administered to the tumor and main nodal drainage over 4-6 weeks, then a 15-25 Gy boost dose is given to the primary tumor bed only. However, postoperative irradiation after complete removal of a gross tumor gives a 10% survival rate only at 2 years. Improvement of these results, are eventually expected from intra-operative irradiation techniques or radiochemotherapy combined treatments.