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Along with the surgeon, the gastroenterologist and the general practitioner, the radiation oncologist is involved in the follow-up of patients with rectal cancer treated by radiation. Post-treatment follow-up is recommended by major professional expert groups and consists of clinical examination, monitoring of carcinoembryonic antigen, colonoscopy and computed tomography of the abdomen and pelvis. Three recent large phase III randomized trials demonstrated a lack of survival benefit from intensive follow-up strategies in comparison with minimal follow-up. However, a follow-up program is not only important for the detection of an early disease relapse but it can be also used for the identification and the management of long-term toxicity and sequalae related to rectal cancer treatment.

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.

Image-guided adaptive brachytherapy (IGABT) is a high-precision radiation that allows defining accurately treatment targets and optimizing their coverage whereas sparing efficiently the surrounding organs at risk. Ten years ago, in a will of harmonizing the reporting of brachytherapy, the Groupe Européen de Curiethérapie - European Society for Radiation Oncology (GEC-ESTRO) published recommendations on target definitions and dosimetric parameters. During the last years, clinical and dosimetric studies supporting their relevance led the International Commission on Radiation Units and Measurements to propose a report on prescribing and reporting. This review aims to highlight the recent advances in IGABT and its future developments.Clinical evidence demonstrating the superiority of IGABT over radiographs-based brachytherapy is accumulating. In parallel, dose-volume effects have been established between dose-volume parameters and tumor response or the occurrence of late radiation morbidity. Preliminary studies indicate that planning aims could be adapted to clinical situations and cofactors. The first publications from the large studies led by the GEC-ESTRO enforce these findings.A trend emerges toward a personalization of treatment with the adaptation of planning aims to prognostic features and the development of individualized applicators. Image-guidance modalities are developed with a better use of MRI or conversely the use of more accessible modalities such as transrectal ultrasound.

Image-guided adaptive brachytherapy is a high precision technique that allows dose escalation and adaptation to tumor response. Two monocentric studies reported continuous dose-volume response relationships, however, burdened by large confidence intervals. The aim was to refine these estimations by performing a meta-regression analysis based on published series.Eligibility was limited to series reporting dosimetric parameters according to the Groupe Européen de Curiethérapie-European SocieTy for Radiation Oncology recommendations. The local control rates reported at 2-3 years were confronted to the mean D90 clinical target volume (CTV) in 2-Gy equivalent using the probit model. The impact of each series on the relationships was pondered according to the number of patients reported.An exhaustive literature search retrieved 13 series reporting on 1299 patients. D90 high-risk CTV ranged from 70.9 to 93.1 Gy. The probit model showed a significant correlation between the D90 and the probability of achieving local control (p0.0001). The D90 associated to a 90% probability of achieving local control was 81.4 Gy (78.3-83.8 Gy). The planning aim of 90 Gy corresponded to a 95.0% probability (92.8-96.3%). For the intermediate-risk CTV, less data were available, with 873 patients from eight institutions. Reported mean D90 intermediate-risk CTV ranged from 61.7 to 69.1 Gy. A significant dose-volume effect was observed (p = 0.009). The D90 of 60 Gy was associated to a 79.4% (60.2-86.0%) local control probability.Based on published data from a high number of patients, significant dose-volume effect relationships were confirmed and refined between the D90 of both CTV and the probability of achieving local control. Further studies based on individual data are required to develop nomograms including nondosimetric prognostic criteria.

Objective To examine the clinical results of a preoperative image-guided pulse-dose-rate brachytherapy (PDR-BT) in early stage cervical cancer. Materials/methods We examined the outcome of consecutive patients with early stage cervical cancer undergoing preoperative image-guided PDR-BT between 2004 and 2013 because of risk factors (lymphovascular embols and/or tumour>2cm). The objective was to deliver 60Gy to 100% of the intermediate risk clinical target volume. Brachytherapy was followed, 6–8weeks later, by a radical hysterectomy/bilateral salpingo-oophorectomy plus pelvic +/− para-aortic lymph node dissection. Patients with positive lymph nodes had postoperative chemoradiation. Results 77 patients met the above criteria of preoperative PDR-BT. On hysterectomy specimen, 54 (70.1%) presented a complete histological response. Four (5.2%) had a tumour residuum⩾1cm. Median follow-up was 46.8months. 5-Year disease-free survival (DFS) rate was 84.4%. Only one local recurrence was observed. The presence of lymph nodal metastases, a tumour size>3cm and a brachytherapy/surgery time interval⩾9weeks correlated with a poorer DFS. Six postoperative complications were encountered (7.8%). Total reference air kerma correlated with late vaginal toxicity ( p =0.02). Conclusions A preoperative image-guided PDR-BT was safe and effective. Predictive factors for survival and toxicity were evidenced.

To report the outcomes and late toxicities of patients with locally advanced cervical cancer treated with concomitant chemoradiation (CRT) followed by intracavitary image-guided adaptive brachytherapy (IGABT).Data from consecutive patients with histologically proven stage IB-IVA cervical cancer treated with curative intent in a single institution were analyzed. After pelvic +/- para-aortic external-beam radiation therapy, they received pulsed-dose rate IGABT following GEC-ESTRO recommendations.Two hundred and twenty-five patients were enrolled. Sixty-five percent were stage≥IIB according to FIGO classification. Ninety-five percent received CRT. Mean D90 to HR and IR-CTV were 80.4+/-10.3Gy and 67.7+/-6.1Gy. After a median follow-up of 38.8months, 3-year local control and overall survival rates were 86.4% and 76.1%, respectively. A trend for a detrimental effect of tumor stage on local control rates was observed with 3-year local control rates of 100% for stages IB1 and IIA, 90.5 for IB2, 85.8% for IIB, 50% for IIIA, 77.1 for IIIB, and 66.7% for IVA tumors (p=0.06). Local control rates at 3years were 95.6% in the group of patients with D90 of HR-CTV≥85Gy, 88.8% in those with D90 between 80 and 85Gy, and 80% when D9080Gy (p=0.018). Eighteen severe late gastrointestinal and urinary effects affecting 14 patients were reported corresponding with a crude incidence of 6.6%.CRT followed by IGABT provides high local control rates with limited toxicity. Reaching high doses is mandatory to achieve local control and interstitial brachytherapy is necessary in advanced diseases.

ObjectiveThe aim of this study was to report our institutional experience of a multimodal approach for treatment of locally advanced high-grade neuroendocrine cervical cancer.Methods and MaterialsPatients with primary locally advanced neuroendocrine cervical cancer diagnosed between 2001 and 2014 were included. The scheduled treatment sequence was as follows: pelvic +/− para-aortic radiotherapy (according to tumor stage), associated with chemotherapy based on platine-derivate and etoposide regimen, followed with a brachytherapy boost, then completion surgery if there was no progression +/− consolidation etoposide chemotherapy (for a total of 5–6 cycles). Disease-free survival (DFS) and overall survival (OS) were reported and prognostic factors were searched.ResultsA total of 24 patients fulfilled inclusion criteria. Median age was 48 (range 22–77 years). Fourteen patients (58%) had pelvic lymph node metastases. After chemoradiation/brachytherapy, a radical hysterectomy could be performed in 18 of 24 patients (75%). Histologically complete resection was achieved in 14 (78%) of 18 patients. Complete pathological response was reported in 7 (39%) of 18. With median follow-up of 29.7 months, 10 (42%) of 24 patients experienced tumor relapse, all associated with distant failure, including one local failure. The DFS and OS rates estimated at 3 years were 55% and 63%, respectively. Lymph node metastases and tumor stage were prognostic for DFS (P = 0.016 and P = 0.022, respectively). Complete resection was associated with a lower incidence of relapses, as compared with microscopically incomplete resection (P = 0.04). A total of 12 (86%) of 14 patients with histologically complete resection were in complete remission at last follow-up. Apart from manageable acute hematological toxicities, most treatment complications were mild to moderate.ConclusionsThis series based on a multimodal management compares favorably with previously published data. Most patients could be eligible to surgery, and complete remission was achieved in 85% of those amenable to complete resection.

To analyze the medical literature devoted to work-up, epidemiology, local control, survival, complications and sequelae after conservative treatment for early-stage squamous cell carcinoma of the tonsillar region. An analysis of the PubMed (1975-2016) database was performed using the following keywords and associations: "tonsil/tonsillar region/oropharynx" AND "squamous cell carcinoma" AND "early-stage (I-II; T1-2N0M0)" AND "radiation therapy/radiotherapy" OR "conservative surgery/oropharyngectomy/transoral surgery/radical tonsillectomy". The search retrieved 10 retrospective series documenting local control and/or survival in series with more than 50 cases and a minimum 2 years' follow-up after conservative treatment; no prospective studies, meta-analyses and/or Cochrane analyses were found. Magnetic resonance imaging is the key radiological exam for local extension assessment. Human papilloma virus infection (HPV) is a risk factor that must be screened for systematically, since it induces tumoral radio-sensitivity and increases the risk of specific synchronous and metachronous second primaries. Whatever conservative treatment used, local control and survival rates higher than 85% were achieved. Implementing intensity-modulated radiation therapy reduced the incidence and severity of radiation-related complications and sequelae. Transoral surgery yielded very low morbidity/mortality rates, enabled association to ipsilateral neck dissection, and allowed radiation therapy to be reserved for the management of metachronous second primaries. Transoral surgery appeared to be the first-line option in the majority of cases. Lifetime follow-up adapted to HPV status is mandatory. The development of HPV vaccination does not mean that campaigns against smoking and alcohol abuse are of diminished importance.

Long-chain 3-hydroxyacyl CoA dehydrogenase deficiency and choroidal neovascularization D. Stopek, E. Gitteau Lala, F. Labarthe, M.L. Le Lez, S. Majzoub, P. Castelnau, P.J. Pisella We report the case of a 9-year-old girl with a long-chain 3-hydroxyacyl CoA dehydrogenase (LCHAD) deficiency. This enzyme participates in mitochondrial fatty acid β-oxidation. Genetic fatty acid oxidation defects induce cellular energetic deficiency, and thus early life-threatening manifestations. An appropriate diet prevents these severe disorders. Nevertheless, LCHAD deficiency is the only β-oxidation enzymatic disorder that induces a chorioretinopathy, predominating at the posterior pole. We describe the first case of bilateral macular choroidal neovascularization. One eye presented a fibrovascular lesion. The other eye presented an active neovascularization stabilized by two dynamic phototherapies. The specificity of choroidal degeneration related to LCHAD deficiency remains unknown. Reviewing of literature and biochemical mechanisms suggests that fatty acid oxidative stress rather than a mitochondrial energetic defect is involved. For practical purposes, this report emphasizes the importance of ophthalmological follow-up of these patients.

Purpose To establish dose–volume effect correlations for late bladder and rectum side effects in patients treated for locally advanced cervical cancer with concomitant chemoradiation followed by pulsed-dose rate image-guided adaptive brachytherapy. Material and methods The dosimetric data, converted in 2Gy equivalent, from 217 patients were confronted to late morbidity defined as any event lasting or occurring 90days after treatment initiation. Toxicity was assessed using the CTC-AE 3.0. Probit analyses and Log rank tests were performed to assess relationships. Results One hundred and sixty-one urinary and 58 rectal events were reported, affecting 98 (45.1%) and 51 (23.5%) patients, respectively. Cumulative incidences for grade 2–4 bladder and rectal morbidity were 24.3% and 9.6% at 3years, respectively. Significant relationships were observed between grade 2–4 and 3–4 events and D0.1cm 3 and D2cm 3 for the bladder and between grade 1–4 and 2–4 event probability and rectal D2cm 3 . The effective doses for 10% grade 2–4 morbidity were 65.3Gy (59.8–81.3), and 55.4Gy (15.7–63.6), respectively, for the rectum and bladder. Without considering urinary and rectal incontinence, for which the pertinence of correlating them with D2cm 3 is questionable, ED10 were 68.5Gy (62.9–110.6) and 65.5Gy (51.4–71.6Gy). When sorting patients according to D2cm 3 levels, patients with high D2cm 3 had significantly lower morbidity free survival rates for grade 1–4 and 2–4 urinary and rectal morbidity. Conclusion Significant dose–volume effect relationships were demonstrated between the modern dosimetric parameters and the occurrence of late rectal and urinary morbidity in patients treated with pulsed-dose-rate brachytherapy. Further studies are required to refine these relationships according to clinical cofactors, such as comorbidities.

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 1 cm 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.

Purpose To report the prognostic factors for local control in patients treated for locally advanced cervical cancer with image guided pulsed-dose rate brachytherapy. Materials/methods Patients treated with curative intent by a combination of external beam radiotherapy and pulsed-dose rate brachytherapy were selected. Local failure was defined as any relapse in the cervix, vagina, parametria, or uterus during follow-up. Prognostic factors were selected based on log rank tests and then analyzed with a Cox model. Dose/effect correlations were performed using the probit model. Results Two hundred and twenty-five patients treated from 2006 to 2011 were included. According to the FIGO classification, 29% were stage IB, 58% stage II, 10% stage III, and 3% stage IVA; 95% received concomitant chemotherapy. Thirty patients were considered having incomplete response or local failure. Among the selected parameters, D90 for HR-CTV, D90 for IR-CTV, the overall treatment time, the TRAK, and the HR-CTV volume appeared significantly correlated with local control in univariate analysis. In multivariate analysis, overall treatment time >55days and HR-CTV volume >30cm 3 appeared as independent. The probit analysis showed significant correlations between the D90 for both CTVs, and the probability of achieving local control ( p =0.008 and 0.024). The thresholds to reach to warrant a probability of 90% of local control were 85Gy to the D90 of the HR-CTV and 75Gy to 90% of the IR-CTV (in 2Gy equivalent, α / β =10). To warrant the same local control rate, the D90 HR-CTV should be significantly increased in stage III–IV tumors, in case of HR-CTV >30cm 3 , excessive treatment time, or tumor width at diagnosis >5cm (97, 92, 105, and 92Gy respectively). Conclusions Overall treatment time and HR-CTV volume were independent prognostic factors for local control. The D90 for HR and IR CTV were significantly correlated with local control, and D90 HR-CTV should be adapted to clinical criteria.

The control of Graves' disease patients treated with antithyroid drugs (ATD) involves monitoring the dose of ATD, the duration of therapy and the prediction of the long-term outcome of the disease. The sequential follow-up of free thyroid hormones and ultrasensitive TSH (USTSH) helps in monitoring of ATD therapy, except in patients complemented with thyroid hormones. The normalization of early thyroid uptake of radioiodine or pertechnetate, which seems to be closely related to circulating thyroid-stimulating immunoglobulins, confirms the remission that leads to stopping ATD therapy. The raise of plasma USTSH in a normal range within the six months following ATD withdrawal is another indicator of remission. However, the post therapeutic course of Graves' patients remains unpredictable: late relapses and hypothyroidism may occur despite the normalization of the pituitary-thyroid axis, leading to a yearly clinical control with USTSH evaluation.