Volumetric evaluation of an alternative bladder point in brachytherapy for locally advanced cervical cancer.

PURPOSE: To evaluate an alternative dose point, so-called ALG (for Alain Gerbaulet), for the bladder in comparison to the International Commission on Radiation Units and Measurements (ICRU) point and D2cm(3) (minimal dose to maximally exposed 2 cm(3)) in a large cohort of patients with locally advanced cervical cancer treated with external beam radiotherapy followed by image-guided pulsed dose rate brachytherapy. METHODS AND MATERIALS: For each patient, the ALG point was constructed 1.5 cm above the ICRU bladder, parallel to the tandem (coronal and sagittal planes). The dosimetric data from 162 patients were reviewed. RESULTS: Average doses to ALG and bladder points were 19.40 Gy ± 7.93 and 17.14 ± 8.70, respectively (p=0.01). The 2 cm(3) bladder dose averaged 24.40 ± 6.77 Gy. Ratios between D2cm(3) and dose points were 1.37 ± 0.46 and 1.68 ± 0.74 (p<0.001) for ALG and ICRU points, respectively. Both dose points appeared correlated with D2cm(3) (p<0.001) with coefficients of determination (R(2)) of 0.331 and 0.399 respectively. The estimated dose to the ICRU point of the rectum was 12.77 ± 4.21 and 15.76 ± 5.94 for D2cm(3) (p<0.0001). Both values were significantly correlated (p<0.0001, R(2) = 0.485). CONCLUSION: The ALG point underestimates the D2cm(3), but its mean on a large cohort is closer to D2cm(3) than the dose to ICRU point. However, it shows great variability between cases and the weak strength of its correlation to D2cm(3) indicates that it is not a good surrogate for individual volumetric evaluation of the dose D2cm(3).

[Toxicity of radiation therapy and antiangiogenics combination: a case report]. / Toxicité de l'association radiothérapie et antiangiogéniques: à propos d'un cas.

The combined administration of antiangiogenic agents (AA) and radiation is being evaluated. No AA has yet received Marketing Authorization in this indication. However, they are widely used in medical oncology and criteria for stopping their administration in case of irradiation have not been defined. We report the case of a 63-year-old man experiencing grade 2 skin toxicity while on radiation treatment and sorafenib (400mg twice daily) for a metastatic lesion developing between the vastus medialis muscle and the cortical of the mid-diaphysis of the right femur. Toxicity occurred at 21Gy, for a total dose of 36Gy (12 fractions of 3Gy). Cutaneous symptoms rapidly disappeared after treatment discontinuation. Radiotherapy alone was resumed after a few days and the total dose could be delivered, with good tolerance. At 2-month follow-up, the intramuscular lesion had regressed. Several other cases of patients with poor tolerance to the association of AA and radiotherapy have been reported. Further studies of the effectiveness and tolerance of the combination treatment are needed before indications for AA can be extended to other diseases.

[Angiogenesis: all a radiation oncologist should know]. / Angiogenèse et radiothérapie : tout ce qu'un oncologue radiothérapeute doit savoir.

Angiogenesis is a crucial requirement for tumorogenesis, providing oxygen and nutrient supply necessary for tumor growth and metastasis. This is a complex phenomenon regulated by many factors that can now be targeted by novel anti-cancer therapies. Antiangiogenic approaches have shown positive results in clinical trials and are now approved as standard of care in medical oncology. Many clinical trials are evaluating antiangiogenic agents in association with radiotherapy. This review aims to summarize the knowledge useful to the understanding of these novel therapies and their potential in combination with radiotherapy.

[Prophylactic cranial irradiation in non-small cell lung cancer]. / Irradiation prophylactique cérébrale dans les cancers bronchopulmonaires non à petites cellules.

Prophylactic cranial irradiation (PCI) has become part of the standard treatment in patients with small cell lung cancer (SCLC) in complete remission. Not only does it decrease the risk of brain recurrence by almost 50%, it has a significant positive effect on survival (5.4 percent increase at 3 years). As the prognosis of patients with locally advanced non-small cell lung cancer (NSCLC) has improved with combined modality treatment, brain metastases have also become an important cause of failure (10 to 30%, approaching 50% in certain studies as in SCLC). Survival after treatment of brain metastases is poor and impact on quality of life of patients is important. As in SCLC, 4 randomised evaluating PCI in NSCLC have been carried out in the seventies and early eighties. If 3 out of 4 trials have shown a significant decrease of brain metastases, none of them demonstrated any impact on survival. Thus PCI cannot be recommended as standard treatment in NSCLC, however new trials would be needed.

Pelvic radiotherapy in the setting of rheumatoid arthritis: Refining the paradigm.

PURPOSE: Conflicting results concerning the toxicity of radiotherapy in the setting of rheumatoid arthritis were reported in literature. This work describes the toxicity profiles of patients with rheumatoid arthritis undergoing pelvic radiotherapy for gynecologic malignancies at our institution. PATIENTS AND METHODS: Charts of patients with rheumatoid arthritis who underwent pelvic radiotherapy for cervical or endometrial cancer in a curative intent at the Gustave-Roussy Cancer Campus between 1990 and 2015 were reviewed for treatment-related toxicities. Acute and late effects were graded as per the Common Terminology Criteria for Adverse Events version 4.0 scoring system. RESULTS: Eight patients with cervical cancer and three with endometrial cancer were identified. Median follow-up was 56 months. Median external beam radiotherapy dose was 45Gy. All patients received a brachytherapy boost using either pulse- or low-dose rate technique. Concomitant chemotherapy was used in seven cases. Median time from rheumatoid arthritis diagnosis to external beam radiation therapy was 5 years. No severe acute gastrointestinal or genitourinary toxicity was reported. One patient had grade 3 dermatitis. Any late toxicity occurred in 7 /11 patients, and one patient experienced severe late toxicities. One patient with overt systemic rheumatoid arthritis symptoms at the time of external beam radiation therapy experienced late grade 3 ureteral stenosis, enterocolitis and lumbar myelitis. CONCLUSION: Pelvic radiotherapy, in the setting of rheumatoid arthritis, appears to be feasible, with potentially slight increase in low grade late events compared to other anatomic sites. Patients with overt systemic rheumatoid arthritis manifestation at the time of radiotherapy might be at risk of potential severe toxicities.

Brachytherapy as part of the conservative treatment for primary and recurrent vulvar carcinoma.

PURPOSE: There are only scarce data on the place of brachytherapy (BT) for treatment of vulvar carcinoma. Our institutional experience of interstitial BT for vulvar carcinoma patients is reported. METHODS AND MATERIALS: Clinical records of patients receiving low-dose-rate or pulsed-dose-rate BT as part of the primary treatment for primary/recurrent vulvar squamous cell carcinoma or as part of postoperative treatment between 2000 and 2015 were included. Patients, tumors, and treatment characteristics as well as clinical outcome were examined. RESULTS: A total of 26 patients treated with BT were identified. BT was delivered as part of primary intent treatment for locally advanced/recurrent cancer in 11 patients and as part of postoperative treatment in 15 patients. Median age at time of BT was 63 years (range, 41-88 years). Pulsed-dose-rate and low-dose-rate were used in 15 patients and 11 patients, respectively. BT was performed as a boost to the tumor bed following external beam radiotherapy (n = 13) or as the sole irradiation modality (n = 13). Total median dose at the level of primary tumor was 60 GyEQD2 (range, 55-60 GyEQD2). With mean followup of 41 months (range, 5 months-11.3 years), 11 patients experienced tumor relapse, and in two of them, site of relapse was only local. Three-year estimated disease-free survival and overall survival rates were 57% (95% confidence interval: 45-69%) and 81% (95% confidence interval: 72-90%), respectively. All toxicities were Grade 2 or less. CONCLUSIONS: Interstitial BT used as part of the primary or postoperative treatment of vulvar carcinoma is feasible with a satisfactory toxicity profile. Prognosis remains, however, dismal, with a high frequency of failures in patients with locally advanced tumors.

[Small cell lung cancer (CPC). Management of patients presenting with limited stage small cell carcinoma of the lung]. / Les cancers à petites cellules. Modalités actuelles de la prise en charge des patients présentant un carcinome bronchique à petites cellules localisé.

Small cell carcinomas represent less than 20% of all lung cancer. Only a third of these patients present with limited stage disease. Treatment is based on a combination of chemotherapy and radiotherapy including a platinum salt with or without another drug. Conformational thoracic radiotherapy is administered either classically fractionated or in an accelerated form. Prophylactic cranial irradiation is indicated in patients with a good response. An improvement in outcomes has been obtained with this regimen. Even in limited stage disease 5 year survival remains about 25% in the best series. The majority of patients will relapse and the risk of cerebral metastases is particularly high, reaching nearly 50% at 2 years even in patients with a complete response. Prophylactic cranial irradiation should be part of the standard management of patients with a complete response on the basis of a meta analysis showing a 5% increase in survival at three years. Even though combination treatments have improved survival, a number of questions remain that should stimulate further clinical trials to establish the optimum regimes of chemotherapy and radiotherapy and the optimum strategies for combining the two. In addition the potential role of targeted therapy in selected patients must be examined.

[Recommendations in case of radiation of patient with a pacemaker or an implantable defibrillator]. / Patients porteurs d'un stimulateur cardiaque ou d'un défibrillateur implantable.

Patients with pacemakers or defibrillators have a relative contra-indication for radiotherapy. This review presents the precautions issued by the French agency for drug safety (ANSM).

[Radiotherapy during pregnancy]. / Radiothérapie et grossesse.

The diagnostic of cancer during pregnancy is a rare and delicate situation. As the developments of the embryo and the human fetus are extremely sensitive to ionizing radiations, the treatment of these tumors should be discussed. The studies - preclinical and clinical - based mostly on exposure accidents show that subdiaphragmatic treatments are possible during pregnancy. When radiotherapy is used, phantom estimations of the dose to the fetus, confirmed by in vivo measurements are required. Irradiation and imaging techniques should be arranged to decrease as much as possible the dose delivered to the fetus and hold below the threshold of 0.1Gy.

CTV to PTV in cervical cancer: From static margins to adaptive radiotherapy.

Intensity-modulated radiotherapy (IMRT) is increasingly used in order to minimize the gastrointestinal, genitourinary, and hematological toxicity in cervical and uterine cancers. However, the benefit of this high-precision approach is detracted by the margins applied to the clinical target volume (CTV) to generate the planning tumor volume (PTV), taking into account tumor and surrounding organs movements, deformations, and volume changes. Adequate PTV margins should be large enough to prevent geographical misses, but not excessive, which might end the benefit from IMRT. The objectives of this review were: (a) to present the evidence available for the determination of CTV-PTV margin for uterine cancers; (b) to highlight the impact of these margins in the context of adaptive radiotherapy; and (c) to discuss the role of the PTV concept in intracavitary brachytherapy.

[Role of radiotherapy in the treatment of NK/T-cell nasal type and primary cerebral lymphomas]. / Place de la radiothérapie dans la prise en charge des lymphomes NK/T de type nasal et primitifs cérébraux.

The head and neck are common sites for extranodal non-Hodgkin lymphomas. Radiotherapy plays an important role in the treatment of low-grade lymphomas, with curative or palliative intent. In the case of high-grade lymphomas, its combination with chemotherapy is debated. Its role is however undeniable in two specific entities: NK/T-cell lymphoma NK/T nasal type, and primary central nervous system lymphomas, which are the subject of this review.

An uncommon cause of dysuria solved by "boom-boom" radiotherapy.

BACKGROUND: Chronic lymphocytic leukaemia is a common disease affecting the hematopoietic organs. The disease remains classically indolent for years preceding a blast crisis. However, the disease can affect all parts of the body. We report here an unusual localization. CASE PRESENTATION: A 72-year-old man was followed for 2 years for an indolent chronic lymphocytic leukaemia while he presented a rapidly progressive dysuria. Prostate biopsies were performed concluding to a prostate involvement by the chronic lymphocytic leukaemia. In the absence of progression according to RAI staging system and Binet's classification, he was treated with local low-dose radiotherapy, twice 2 Gy, allowing for a rapid resolution of the symptoms. No systemic treatment was introduced, and 1 year after the completion of his treatment, he is still under watchful waiting strategy for his chronic lymphocytic leukaemia. CONCLUSION: Low-dose radiotherapy is an underused effective strategy in indolent lymphoma. In this case, urinary symptoms from a prostate involvement were relieved non-invasively at low cost.

45 or 50 Gy, Which is the Optimal Radiotherapy Pelvic Dose in Locally Advanced Cervical Cancer in the Perspective of Reaching Magnetic Resonance Image-guided Adaptive Brachytherapy Planning Aims?

AIMS: In locally advanced cervical cancer, the dose delivered results from the sum of external beam radiotherapy and brachytherapy, and is limited by the surrounding organs at risk. The balance between both techniques influences the total dose delivered to the high-risk clinical target volume (HR-CTV). The aim of the present study was to compare the ability of reaching different planning aims after external beam radiotherapy pelvic doses of 45 Gy in 25 fractions or 50.4 Gy in 28 fractions, both considered as standard prescriptions. MATERIALS AND METHODS: The optimised plans of 120 patients treated with pelvic chemoradiation followed by magnetic resonance image-guided intracavitary brachytherapy were reviewed. The doses per pulse were calculated, and the number of pulses required to reach the planning aims, or a limiting dose constraint to organs at risk, was calculated. All doses were converted to 2-Gy equivalents. Three scenarios were applied consisting of different sets of planning aims: 85 and 60 Gy for the HR-CTV and the intermediate-risk CTV (IR-CTV) D90 (minimal dose received by 90% of the volume) in scenario 1, 90 and 60 Gy, respectively, for scenarios 2 and 3. For organs at risk, dose constraints were 90, 75 and 75 Gy to the bladder, rectum and sigmoid D2cm(3), respectively, in scenarios 1 and 2, and 80, 65 and 70 Gy in scenario 3. RESULTS: A similar HR-CTV D90 could have been reached in scenarios 1 and 2 according to both pelvic doses. In scenario 3, a higher mean HR-CTV could have been reached in the 45 Gy arm (83.5 ± 8.0 versus 82.4 ± 8.0, P < 0.0001). The mean D2cm(3) of organs at risk was systematically and significantly increased after a delivery of 50.4 Gy to the pelvis, from 0.9 to 2.89 Gy. The proportions of plans reaching planning aims were 85.8, 72.5 and 42.5% after 45 Gy and 85.5, 67.5 and 33.3% after 50.4 Gy according to scenarios 1, 2 and 3, respectively. According to scenario 3, 50.4 Gy, the reachable HR-CTV D90 was higher in 30% of the cases, by 2 Gy in two cases. Those cases were unpredictable and due to unfavourable organs at risk topography and poor response to external beam radiotherapy. CONCLUSION: The delivery of 45 Gy in 25 fractions to the pelvis before brachytherapy warrants a higher probability to reach brachytherapy planning aims, in comparison with 50.4 Gy in 28 fractions.

[French experience in paediatric total body irradiation: A study from the radiotherapy committee of the Société française des cancers de l'enfant (SFCE)]. / Expérience française de l'irradiation corporelle totale en pédiatrie : étude du comité de radiothérapie de la Société française des cancers de l'enfant (SFCE).

A survey was conducted in 2015 in France on the care of children in radiotherapy services. We present the results for total body irradiation in children, a specific technique of radiation treatment, which needs dedicated controls for this particular population. Of the 17 centres interviewed, 16 responded, and 13 practiced total body irradiation. Patients are positioned in lateral decubitus in 11 centres and supine/prone in two centres. Doses used for total body irradiation in myeloablative bone marrow transplantation are the same in all centres (12Gy); treatments are always fractionated. Lung shielding is positioned to limit the dose at an average of 8Gy with extremes ranging from 6 to 10Gy. The shape of the shieldings varies depending on departments' protocol, with a smaller size in case of mediastinal mass. Four centres have experience of total body irradiation under general anaesthesia, despite twice-daily fractions. In total, practice is relatively homogeneous throughout France and is inspired by the knowledge obtained in adults.

[Follow-up after radiation therapy for cervical cancer]. / Suivi après radiothérapie pour un cancer du col utérin.

Radiation therapy plays a central role in treatment strategies of cervical cancer. Follow-up after external pelvic radiation therapy and brachytherapy is based upon French and international specific recommendations. It aims to assess early tumour response, and to detect local or metastatic recurrences which can be suitable for salvage treatment. Follow-up after radiation therapy for cervical cancer should also assess gastro-intestinal, urinary and sexual toxicities which may have an impact on quality of life. This is a major concern in the evaluation of the results of intensity-modulated radiation therapy (IMRT) and MRI-guided brachytherapy, which should lead to a better local control and to a better bowel tolerance.

Interstitial pulsed-dose-rate brachytherapy for the treatment of squamous cell anal carcinoma: A retrospective single institution analysis.

OBJECTIVE: To examine the outcome of patients receiving interstitial pulsed-dose-rate brachytherapy (PDR-BT) after pelvic radiation therapy for treatment of an anal squamous cell carcinoma. METHODS AND MATERIALS: Twenty-one patients were identified: 13, six, and two with stages I, II, and III tumors, respectively. After receiving received pelvic irradiation +/- concurrent chemotherapy, patients were delivered a PDR-BT boost to the residual tumor, with intention to deliver a minimal total dose of 60 Gy. The greatest dimension of residual tumor at the time of brachytherapy procedure was 12.5 mm (range: 0-20 mm). Brachytherapy implantation was performed according to the Paris system, only one plane implant being used. RESULTS: Median dose delivered through BT was 20 Gy (range: 10-30 Gy). Median number of pulses was 48 (range: 20-80 pulses). Median treated volume was 9 cm(3) (range: 5-16 cm(3)). Median dose per pulse was 40 cGy (range: 37.5-50 cGy). No Grade 3 or more acute toxicity was reported. No Grade 3 or more delayed toxicity was seen among 18 patients with more than 6 months follow-up. Median followup was 47 months (range: 6-73 months). Twenty patients (95%) were alive at last follow-up. Tumor relapses were experienced in four patients (19%), including local relapse in three patients (14%). CONCLUSION: With almost 4 years median followup, this study confirms previous data suggesting that PDR-BT is effective and safe in this indication. Local control rate and toxicity were in the range of what was seen with continuous low-dose-rate BT.

Implementation of the global risk analysis in pulsed-dose rate brachytherapy: methods and results.

PURPOSE: To report the application of the global risk analysis (GRA) in the pulsed-dose rate (PDR) brachytherapy workflow. MATERIAL AND METHODS: Analyses were led by a multidisciplinary working group established within the unit with the guidance of a quality engineer. First, a mapping of hazardous situations was developed as a result of interactions between the patient workflow for a treatment using PDR brachytherapy split into 51 sub-phases with a comprehensive list of the hazards that he/she faces (44). Interactions, when relevant, were sorted by level of priority: to be treated immediately, secondarily (the group is not entitled to treat the situation), or later (safe situation). Secondly, for each high priority dangerous situation, scenarios were developed to anticipate their potential consequences. Criticality was assessed, using likelihood and severity scales and a matrix, which allocated risks into categories: acceptable (C1), tolerable under control (C2) and unacceptable (C3). Then, corrective actions were proposed and planned when relevant, after assessment of their feasibility with a scale of effort. Finally, the criticality of the scenarios was reevaluated, taking into account the implementation of these actions, leading to a residual risk mapping, which could trigger additional proposals of actions. RESULTS: Two thousand one hundred and eighty-four potential interactions between the list of hazards and the workflow were analyzed. Mapping of dangerous situations identified 213 relevant interactions, from which 61 were considered with high priority. One hundred and twenty-six scenarios were generated: 68 with a low criticality (74.3%), 58 with an intermediate score (25.7%). No scenario with the highest criticality was individualized. Twenty-one corrective actions were planned. Mapping of residual risk resulted in the disappearance of most C2 risks, leaving 5 C2 scenarios (4%), for which four monitoring indicators were implemented in addition to the corrected actions decided on. CONCLUSION: The implementation of the GRA appeared feasible, and led to implement 21 corrective actions, based on scenarios and not on incidents.

What to expect from immediate salvage hysterectomy following concomitant chemoradiation and image-guided adaptive brachytherapy in locally advanced cervical cancer.

PURPOSE: Concomitant chemoradiation followed by brachytherapy is the standard treatment for locally advanced cervical cancers. The place of adjuvant hysterectomy remains unclear but tends to be limited to incomplete responses to radiotherapy or local relapse. The aim was to analyse the benefit from immediate salvage surgery following radiation therapy in incomplete responders. METHODS: Among the patients with locally advanced cervical cancer treated with concomitant chemoradiation followed by 3D image-guided adaptive brachytherapy and hysterectomy, cases with genuine macroscopic remnant, defined as at least 1cm in width, were identified. Their clinical data and outcomes were retrospectively reviewed and compared to the patients treated with the same modalities. RESULTS: Fifty-eight patients were included, with a median follow-up of 4.2 years. After hysterectomy, 9 patients had macroscopic residual disease, 10 microscopic and the remaining 39 patients were considered in complete histological response. The 4-year overall survival and disease-free survival rates were significantly decreased in patients with macroscopic residual disease: 50 and 51% versus 92% and 93%, respectively. Intestinal grades 3-4 toxicities were reported in 10.4% and urinary grades 3-4 in 8.6% in the whole population without distinctive histological features. Planning aims were reached in only one patient with macroscopic residuum (11.1%). In univariate analysis, overall treatment time (>55 days) and histological subtype (adenocarcinomas or adenosquamous carcinomas) appeared to be significant predictive factors for macroscopic remnant after treatment completion (P=0.021 and P=0.017, respectively). In multivariate analysis, treatment time was the only independent factor (P=0.046, odds ratio=7.0). CONCLUSIONS: Although immediate salvage hysterectomy in incomplete responders provided a 4-year disease-free survival of 51%, its impact on late morbidity is significant. Efforts should focus on respect of treatment time and dose escalation. Adenocarcinoma might require higher high-risk clinical target volume planning aims.

Clinical Experience with Pulse Dose Rate Brachytherapy for Conservative Treatment of Penile Carcinoma and Comparison with Historical Data of Low Dose Rate Brachytherapy.

AIMS: To assess the efficacy of pulse dose rate (PDR) interstitial brachytherapy in the treatment of carcinoma of the penis and to compare with historical data of low dose rate (LDR) brachytherapy. MATERIALS AND METHODS: We reviewed the clinical records of 27 consecutive patients treated in our institution with exclusive PDR brachytherapy for a squamous cell carcinoma of the penis. The median tumour greatest diameter was 20 mm (range: 10-50 mm). Twenty-three patients (85%) had tumours limited to the glans and/or prepuce and four patients (15%) also had inguinal lymph node metastases. Implantations were carried out according to the Paris system and treatments were delivered with PDR brachytherapy. RESULTS: The median brachytherapy dose was 60 Gy (range: 60-70 Gy). The median treated volume was 28 cm(3) (range: 8-62 cm(3)). The median reference isodose rate was 0.4 Gy/pulse/h (range: 0.4-0.5 Gy/pulse/h). The median number of pulses was 150 (range: 120-175 pulses). With a median follow-up of 33 months (range: 6-64 months), tumour relapses in the penis were reported in four patients (15%). All patients with only local relapse (n = 3) were successfully salvaged with partial amputation. The estimated overall survival rate at 3 years was 95% (95% confidence interval: 83-100%). No grade 3 or more acute reaction was observed. Delayed ulcerations and stenoses requiring at least one meatal dilatation were reported in two (9%) and five (22%) patients without local relapse. The treated volume was significantly correlated to the risk of clinically relevant delayed toxicity. CONCLUSIONS: The efficacy/toxicity results of PDR brachytherapy for the treatment of penile carcinoma are comparable with those obtained with LDR brachytherapy in historical cohorts.