Anti-PD-1 immunotherapy in combination with sequential involved-site radiotherapy in heavily pretreated refractory Hodgkin lymphoma.

The purpose of this study was to assess efficacy and tolerance of anti-programmed death (PD)-1 immunotherapy in combination with sequential involved-site radiotherapy in heavily pretreated refractory Hodgkin lymphoma. In this case series, we reported the outcome of four heavily pretreated patients with refractory Hodgkin lymphoma treated by anti-PD-1 immunotherapy and involved site radiation therapy. After a median follow-up of 13-month, all patients were alive with complete metabolic response. After radiotherapy, all four patients experienced lung toxicity, which was resolved after antibiotherapy with or without corticosteroid treatment. Anti-PD-1 immunotherapy followed by involved-site radiotherapy is feasible and showed very encouraging results in heavily pretreated patients.

[Neuroendocrine carcinoma of the digestive tract: a literature review]. / Carcinome neuro-endocrine du tractus digestif : revue de la littérature.

Neuroendocrine carcinoma is a rare and agressive malignant tumor, mainly developing at the expense of the respiratory and of the digestive tract. Among the digestive tract, appendix, small bowel, and pancreas are the preferential sites of involvement, other locations have been more rarely reported. Neuroendocrine digestive tumors may present with various symptoms in relationship with their localization and a complex pathophysiology. Diagnosis is often made at an advanced stage, explaining partly the bad prognosis of these tumors. The optimal management of digestive neuroendocrine tumors is rendered difficult by their rarity and by a low number of randomized trials. We review the literature regarding epidemiologic and prognostic features of these rare tumors, their diagnostic and therapeutic care. Potential complications are also discussed.

[Single center experience of (18F)-fluorocholine positron emission tomography: analysis of its impact on salvage local therapy in patients with prostate adenocarcinoma]. / Expérience monocentrique de la tomographie par émission de positons à la (18F)-fluorocholine : analyse de son impact sur les indications de traitement local de rattrapage dans la prise en charge des adénocarcinomes prostatiques.

PURPOSE: To assess usefulness of ((18)F)-fluorocholine positron emission tomography (PET) for localizing relapse in patients with biochemical relapse from prostate adenocarcinoma and its impact on indications of salvage local therapy. PATIENTS AND METHODS: An ((18)F)-fluorocholine PET coupled with computed tomography was performed in 28 patients with biochemical progression from prostate adenocarcinoma. At the time of ((18)F)-fluorocholine PET, median prostate specific antigen (PSA) was 3.0 ng/mL (from 0.34 to 93 ng/mL) and 17 patients (60.7%) received hormone therapy. Eighteen patients from this cohort were potentially candidates to salvage radiotherapy. RESULTS: A pathologic uptake was shown in 11 patients (39.3%) and 17 patients (60.7%) had no pathologic uptake. Median PSA was 2.4 ng/mL (0.33 to 36 ng/mL) in case of negative ((18)F)-fluorocholine PET, versus 6.75 ng/mL (1.21 to 93 ng/mL) in case of pathologic uptake (P=0.04). Among the 17 patients candidates to salvage radiotherapy, ((18)F)-fluorocholine PET helped deciding for salvage radiotherapy in five patients, since it showed only centropelvic pathologic uptake (27.7%). In one patient, it showed metastatic and radiotherapy was contraindicated. After prostatectomy, ((18)F)-fluorocholine PET was positive in only one patient candidate to salvage radiotherapy (9.1%), showing anastomotic relapse. CONCLUSION: ((18)F)-fluorocholine was positive in about a third of patients with biochemical progression. Its clinical impact is being prospectively investigated.

Granulocytic sarcoma in a nonleukemic patient: place of radiotherapy and systemic therapies.

Granulocytic sarcoma is a rare extramedullary tumour, which most often occurs in the course of an acute or chronic leukaemia or myeloproliferative disorders. Rarely it is found before peripheral blood or bone marrow evidence of leukemia is present. We report an unusual case of acute paraplegia at first presentation of a spinal epidural granulocytic sarcoma without any haematological disorder. Therapeutic strategies are discussed in the light of the literature.

[Mechanisms of resistance to molecular targeted therapies in breast cancer: update and future]. / Mécanismes de résistance aux thérapeutiques moléculaires ciblées dans le cancer du sein : constats et perspectives.

The importance of targeted therapies has been emphasized by clinical trials using antiangiogenic or HER2 inhibitors in breast cancer. First with trastuzumab, it was demonstrated that targeted therapies may improve outcome in patients with HER overexpressing breast cancer in metastatic or adjuvant settings. The emerging role for angiogenesis inhibitors has also been demonstrated with bevacizumab. Unfortunately, there is growing clinical and biological evidence that tumour cells may develop unexpected and complex mechanisms of resistance to those targeted therapies. This review outlines the mechanisms by which tumour cells may resist to new targeted agents. Most recent developments are also highlighted.

[Impact of radiotherapy on fertility in female patients]. / Impact de la radiothérapie sur la fertilité féminine.

Although insufficiently documented, the impact of radiation therapy on fertility should not be neglected in female patients. Toxicity on reproductive function is dual and is characterized by both mechanistic deleterious effects on the genital tract and partial or complete loss of ovarian function. Moreover, gonadic toxicity may be increased by the concurrent use of chemotherapy or surgical procedure. In some circumstances, ovarian transposition may be justified for young patients. But no compromise may be accepted in terms of carcinologic results. At least, the effect of low-doses of irradiation has not been demonstrated for extra-pelvic radiotherapy.

[Positron emission tomography in the management of cervix cancer patients]. / Tomographie par émission de positons dans la prise en charge des cancers du col de l'utérus.

Since its introduction in clinical practice in the 1990's, positron emission tomography (PET), usually with (18)F-fluoro-2-deoxy-D-glucose ((18)F-FDG), has become an important imaging modality in patients with cancer. For cervix carcinoma, FDG-PET is significantly more accurate than computed tomography (CT) and is recommended for loco-regional lymph node and extrapelvic staging. The metabolic dimension of the technique provides additional prognostic information. Ongoing studies now concentrate on more advanced clinical applications, such as the planning of radiotherapy, the response evaluation after the induction of therapy, the early detection of recurrence. Technical innovations, such as PET cameras with better spatial resolution and hybrid positron emission tomography/computed tomography (PET-CT), available now on the whole territory, provide both anatomic and metabolic information in the same procedure. From the point of view of biological metabolism, new radiopharmaceutical probes are being developed. Those hold promise for future refinements in this field. This article reviews the current applications of FDG-PET in patients with cervix cancer.

[Radiotherapy of maxillary sinus carcinoma: state of art]. / Radiothérapie des carcinomes des sinus maxillaires: l'état de l'art.

Maxillary sinus carcinomas are rare malignancies of the face, characterized by high local relapsing rate. Modalities of treatment are without consensus and respective roles of radiation therapy and surgery remain controversial. As those malignancies are often diagnosed at locally advanced stage, radiation therapy may frequently be used for patients having unresectable advanced disease. Nevertheless, surgery remains treatment of choice for more localized malignancies, in association with systematic postoperative radiotherapy. For those patients whose prognosis remains pejorative, it is necessary to precise the role of radiotherapy in first intention for inoperable tumors, to define necessity for nodal treatment performing and evaluate the place of neoadjuvant or concomitant chemotherapy in a multimodal strategy.

The use of computed tomography in radiotherapy treatment planning for breast cancer. How does conventional radiotherapy planning compare with virtual?

PURPOSE: To compare, in terms of ballistics and dosimetry, a conventional and a virtual simulation in 14 patients without changing the set-up. PATIENTS AND METHODS: 14 women with breast cancer were treated with postoperative radiotherapy from October 2003 to November 2004. Whole breast irradiation alone was indicated (50 Gy at International Committee on Radiation Units [ICRU] point in 25 fractions over 5 weeks) with, in some cases, an additional boost of 16 Gy to the tumor bed--that was not taken into account in this study. After CT scan, tangential fields were conventionally simulated using a Mecaserto Phebus-type simulator-CT scan. The planning target volume (PTV) was the clinical target volume (CTV) expanded with an additional margin of 1 cm in all directions but towards the skin. Both the lungs and the heart were delineated as organs at risk. Dosimetries were computed for the two beams arrangements i.e. 2D conventional and 3D virtual. RESULTS: The mean age of 14 women was 51.4 years (range 26-65). Laterality was the left breast for 6 patients and the right for 8. Few differences were noticeable in terms of gantry angles. The 3D medial fields were more medial with a mean of 8 mm (range 0-15). The 3D lateral fields were more posterior with a mean difference of 8 mm (range 0-25). The dosimetry analysis showed that, with regard to conventional simulations, at least 95% of the CTV received in all cases > 95% of the prescribed dose. However, in 8 out of 14 patients (57%), 15% of the PTV received < 95% of the prescribed dose. The ICRU 50 quality criterion that at least 95% of the PTV (PTV(95%)) should receive at least 95% of the prescribed dose was never met with conventional simulation. In the case of virtual simulation, the ballistics of the treatment were designed to meet the ICRU quality criterion and thus the PTV95% was higher here than with the conventional simulation by a mean of 17.6% +/- 9.7%. The percentage of CTV receiving a dose higher than 107% of the prescribed dose was 21.3% +/- 12% with conventional and 24% +/- 11% with virtual simulation. CONCLUSION: The high incidence of breast cancer, the essential role of radiotherapy in its treatment and the potential ensuing toxicity explain why so many studies are devoted to the improvements brought to the techniques of this treatment. The virtual planning of the treatment, however, comes up against many difficulties. The countering of the CTV is complex and necessitates a combination of clinical examination and imagery. The choice of margins around the CTV has not been standardised and is largely dependent both on the equipment used and the quality control methods.

[Prostate cancer and disseminated intravascular coagulation: review of the literature]. / Cancer de prostate et coagulation intravasculaire disséminée: une revue de la littérature.

Disseminated intravascular coagulation is a rare complication of prostatic cancer evolution. Occurring on hormonorefractory phase, it remains most often infraclinic. Cases of acute, severe intravascular disseminated coagulation at first presentation are life-threatening because of hemorragic and thrombotic complications, justifying emergency medical treatment. In the light of a review of literature, we insist on epidemiological features, physiopathology and therapeutics of intravascular disseminated coagulation. In spite of a pejorative prognosis, this could help to achieve a period of remission.

[Cancer chemotherapy of the upper aerodigestive tract]. / Chimiothérapie des cancers des voies aérodigestives supérieures.

Tumours of the upper aerodigestive tract represent the sixth most frequent kind of cancer in France and throughout the world. If the localised forms may be controlled in the long run in two thirds of cases by surgery or radiotherapy, only one third of locally advanced forms are accessible to a cure after association from radiotherapy and chemotherapy. Besides, with a median of survival less than six months, metastatic tumours present a catastrophic spontaneous prognosis among patients with a medical ground that is often heavily deteriorated by prolonged exposure to alcohol and tobacco. Thus, there is a necessity to implement adapted therapeutic strategies to each patient and based on satisfactory proof levels of effectiveness. Optimisation of existing chemotherapy protocols and development of new therapies, in particular of targeted therapies, remain an important objective in the hope to improve results of treatments in locally advanced and metastatic cancers of the oral cavity.

[Favorable outcome of gemcitabine-induced acute respiratory distress syndrome]. / Syndrome de détresse respiratoire aiguë à la gemcitabine d'évolution favorable.

Gemcitabine is a new important drug used to treat solid tumors including non-small cell lung cancer, pancreatic, bladder and breast cancers. Myelosuppression is the most common adverse effect. Pulmonary toxicity is rare and usually mild and self-limiting with acute dyspnea. Severe pneumonitis and potentially fatal acute respiratory distress syndrome (ARDS) have been described in patients treated for a non-small cell lung cancer. We report a case of gemcitabine-induced ARDS in a 72-year old patient treated with gemcitabine and cisplatin for a bladder cancer without lung metastasis. Administration of high doses of corticosteroids led to a prompt symptomatic improvement.

[Testicular germ-cell tumour: diagnosis and treatment]. / Tumeurs germinales séminomateuses du testicule: diagnostic et traitement.

Among germ cell tumours, seminomas hold a particular status related to their radio-sensitivity. Although radiotherapy remains the best treatment for Localized tumours of stage 1, in some cases, surveillance or chemotherapy may presently be considered as alternative therapies. Due to Long-term radiotherapy-related adverse effects, in particular the risk of second non-germ malignancies or cardiac morbidity, both dose and irradiation field are reduced in case of lymphatic retroperitoneal extension. Chemotherapy is the preferential treatment in more advanced stages, either with retroperitoneal bulky disease or with metastatic extension. Its efficacy allows Limiting surgical indications on residual masses, relying partly on the follow-up data of positron emission transaxial tomography assessment.

[Comparison of classic simulation and virtual simulation in breast irradiation: prospective study on 14 patients]. / Comparaison simulation classique-simulation virtuelle au cours d'une irradiation mammaire: étude prospective sur 14 patientes.

PURPOSE: To compare conventional 2D simulation and virtual simulation on 14 patients with breast cancer. PATIENTS AND METHODS: Patients were simulated for treatment using standard procedure. They subsequently underwent CT scan in the treatment position. The CTV was defined as breast tissue. The PTV was obtained by adding a 3D margin of 1 cm around CTV. Organs at risk (lungs and heart) were outlined. Ballistics and dose distribution obtained with the two planning methods were compared. RESULTS: With conventional simulation, 95% of CTV received 95% of the dose prescribed. Virtual simulation significantly improved dosimetric coverage of PTV without increasing irradiation volume of lung and heart. In 2D simulation, using three slices allowed optimisation by adjusting wedge angle. The five-slice plan was a much better predictor of the maximum dose regions when compared to the three-slice plan. Using entire CT data didn't give any benefit. CONCLUSION: Variations in CTV delineation and PTV definition limit interest of virtual simulation. In classic simulation, a 5 CT slice-plan can be used to optimise dose distribution.

[Combined chemotherapy and radiation therapy for intracranial germinomas. The Val-de-Grace hospital experience]. / Intérêt de la chimiothérapie néoadjuvante dans le traitement des séminomes purs intracérébraux: expérience de l'hôpital du Val-de-Grâce.

Optimal management of intracranial germinomas remains controversial. Focal irradiation to the primary tumor followed by prophylactic craniospinal radiotherapy represents the traditional treatment resulting in excellent long-term survival but potential late effects. To decrease late effects related to extensive fields of radiotherapy, combined chemotherapy and irradiation has been tested with reduced volumes and doses of radiation therapy. We report our experience about four patients successfully treated by neoadjuvant chemotherapy with carboplatin and etoposide followed by radiotherapy delivering 26 to 36 Gy to the whole brain and 36 to 50 Gy to the initial tumor volume.

[Radiotherapy in stage I testicular seminoma: retrospective study and review of literature]. / Radiothérapie des séminomes testiculaires de stade I : étude rétrospective et revue de la littérature.

INTRODUCTION: Seminoma accounts for about 40% of germ cell tumours of the testicle. In this retrospective analysis, we review literature concerning management of stage I seminoma. MATERIALS AND METHODS: Between March 1987 and April 2001, 65 patients with stage I pure testicular seminoma received adjuvant radiotherapy with a 25 MV linear accelerator. RESULTS: Median age was 33 years. Testicular tumour has been found on the right testis in 39 patients and on the left one in 24 patients. Patients have been treated using an anterior-posterior parallel pair and have received 20-25 Gy in 10-14 fractions. The target volume consisted of paraaortic, and paraaortic + homolateral iliac lymph nodes in 17 and 46 patients, respectively. Acute toxicity was mainly digestive, 38% of patients presenting nausea and vomiting. Median follow-up time was 37 months. All patients are alive in complete remission. DISCUSSION: Because of good radio-sensitivity of seminoma, radiotherapy is regarded as standard adjuvant treatment (5 years relapse rate: 3-5%). Acute toxicity is dominated by moderate gastro-intestinal side effects. Secondary neoplasia represents one of the worst possible long-term complications of therapy. Waiting for ongoing randomised trials, the modern literature for seminoma reflects a trend toward lower radiation doses (20-25 Gy) and smaller treatment volumes (paraaortic field). Adjuvant chemotherapy with two courses of carboplatin, might be equivalent to radiotherapy but must be investigated in randomised trials. A surveillance policy is one of the other management options less recommended.

[Hepatitis B, C, and E in New Caledonia. Seroepidemiologic study in military recruits]. / Hepatites B, C et E en Nouvelle-Calédonie. Etude séro-épidémiologique chez les appelés du contingent.

A seroepidemiological study in army conscripts was carried out to collect data on hepatitis B, C, and E in New Caledonia. All young men recruited between October 1998 and June 1999 (n = 351) were retrospectively included in study. Anamnestic data was obtained during the induction physical examination. Blood tests to detect viral markers and assessment of liver function were performed in all cases. The incidence of hepatitis B was 6.6 p. 100 of chronic carriers of HB antigens. The overall number of vaccinated subjects was low, i.e., 17.9 p. 100. The incidence of carriers presenting at least anti-HBc antibodies was higher in persons of Melanesian and Wallisian extraction, i.e. 59.5 p. 100 and 49.2 p. 100 respectively. This is logical since vaccination rates in these ethnic groups were lower. The incidence was also higher in the northern province and islands, i.e., 48.7 p. 100 and 75 p. 100. Mention of a family history of hepatitis B was a significant predictor of infection. No case of hepatitis C was found. Six carriers of anti-HVE were identified including three who had never left New Caledonia. Detection tests for viral RNA were negative in all cases. This study confirms the high incidence of hepatitis B in New Caledonia and the need for mass vaccination. Findings also suggest that the area may still be free of hepatitis C but the presence of hepatitis E cannot be ruled out.