Brachytherapy: An overview for clinicians.

Brachytherapy is a specific form of radiotherapy consisting of the precise placement of radioactive sources directly into or next to the tumor. This technique is indicated for patients affected by various types of cancers. It is an optimal tool for delivering very high doses to the tumor focally while minimizing the probability of normal tissue complications. Physicians from a wide range of specialties may be involved in either the referral to or the placement of brachytherapy. Many patients require brachytherapy as either primary treatment or as part of their oncologic care. On the basis of high-level evidence from randomized controlled trials, brachytherapy is mainly indicated: 1) as standard in combination with chemoradiation in patients with locally advanced cervical cancer; 2) in surgically treated patients with uterine endometrial cancer for decreasing the risk of vaginal vault recurrence; 3) in patients with high-risk prostate cancer to perform dose escalation and improve progression-free survival; and 4) in patients with breast cancer as adjuvant, accelerated partial breast irradiation or to boost the tumor bed. In this review, the authors discuss the clinical relevance of brachytherapy with a focus on indications, levels of evidence, and results in the overall context of radiation use for patients with cancer.

[Building the emotional skills of caregivers for a better workplace environment]. / Compétences émotionnelles et mieux-être au travail.

Emotional skills refer to the ability to identify, understand, express, use one's emotions and those of others. For caregivers, who are experiencing increasingly stressful work conditions and who are accompanying people going through painful moments in their lives, emotional skills are a valuable tool. They make it easier to take a step back from the professional and personal experience and thus promote a better quality of life at work. They concern health students in their initial training.

Association between physical activity and the expression of mediators of inflammation in normal breast tissue among premenopausal and postmenopausal women.

Physical activity is associated with decreased breast cancer risk. The underlying biological mechanisms could include the reduction of the local inflammation in the breast tissue. We conducted a cross-sectional study to assess the association between the physical activity and the protein expression levels of eleven mediators of inflammation in normal breast tissue of 164 women having breast cancer. Information on total physical activity (household, occupational and recreational) performed during a one-year period was collected using a questionnaire. Normal breast tissue was obtained from mastectomy blocks distant from the tumor. The expression of the mediators of inflammation in normal breast tissue was visually evaluated by immunohistochemistry. Multivariate linear regression analyses were used to assess the prevalence ratios (PR) and 95% confidence intervals (CI) for higher protein expression levels of the mediators of inflammation in normal breast tissue across quartiles of physical activity. Higher total physical activity was associated with lower expression levels of the pro-inflammatory mediator TNF-α in normal breast epithelial tissue among all (PR=0.64, 95% CI=0.44-0.93 for the fourth quartile; Ptrend=0.013), premenopausal (PR=0.61, 95% CI=0.41-0.91 for the fourth quartile; Ptrend=0.014) and postmenopausal women (PR=0.45, 95% CI=0.21-0.96 for the fourth quartile; Ptrend=0.022). Conversely, higher total physical activity was associated with higher expression levels of the anti-inflammatory mediator IL-10 in normal breast epithelial tissue among all (PR=1.66, 95% CI=0.97-2.85 for the fourth quartile; Ptrend=0.071) and postmenopausal women (PR=4.69, 95% CI=1.26-17.43 for the fourth quartile; Ptrend=0.010). Our findings suggest a beneficial effect of physical activity on the local inflammatory profile in the breast tissue.

Dose-volume effects in pathologic lymph nodes in locally advanced cervical cancer.

OBJECTIVE: In cervical cancer patients, dose-volume relationships have been demonstrated for tumor and organs-at-risk, but not for pathologic nodes. The nodal control probability (NCP) according to dose/volume parameters was investigated. MATERIAL AND METHODS: Patients with node-positive cervical cancer treated curatively with external beam radiotherapy (EBRT) and image-guided brachytherapy (IGABT) were identified. Nodal doses during EBRT, IGABT and boost were converted to 2-Gy equivalent (α/ß = 10 Gy) and summed. Pathologic nodes were followed individually from diagnosis to relapse. Statistical analyses comprised log-rank tests (univariate analyses), Cox proportional model (factors with p ≤ 0.1 in univariate) and Probit analyses. RESULTS: A total of 108 patients with 254 unresected pathological nodes were identified. The mean nodal volume at diagnosis was 3.4 ±â€¯5.8 cm3. The mean total nodal EQD2 doses were 55.3 ±â€¯5.6 Gy. Concurrent chemotherapy was given in 96%. With a median follow-up of 33.5 months, 20 patients (18.5%) experienced relapse in nodes considered pathologic at diagnosis. Overall nodal recurrence rate was 9.1% (23/254). On univariate analyses, nodal volume (threshold: 3 cm3, p < .0001) and lymph node dose (≥57.5 Gyα/ß10, p = .039) were significant for nodal control. The use of simultaneous boost was borderline for significance (p = .07). On multivariate analysis, volume (HR = 8.2, 4.0-16.6, p < .0001) and dose (HR = 2, 1.05-3.9, p = .034) remained independent factors. Probit analysis combining dose and volume showed significant relationships with NCP, with increasing gap between the curves with higher nodal volumes. CONCLUSION: A nodal dose-volume effect on NCP is demonstrated for the first time, with increasing NCP benefit of additional doses to higher-volume nodes.

Optimizing Local Control in High-Grade Uterine Sarcoma: Adjuvant Vaginal Vault Brachytherapy as Part of a Multimodal Treatment.

PURPOSE: The phase III European Organization for Research and Treatment of Cancer 55874 study has shown that external beam radiotherapy (EBRT) given as adjuvant treatment decreased locoregional recurrences from 40% to 20% in patients (pts) with localized uterine sarcomas (US). No data exist, however, on the place of brachytherapy (BT). MATERIAL AND METHODS: We conducted a single-center retrospective analysis of pts receiving adjuvant BT of the vaginal vault based on the vaginal mold technique as part of their multimodal adjuvant treatment for a high-grade US from 1985 to 2015. Treatment characteristics, patterns of relapse, and toxicity were examined. RESULTS: Median follow-up time was 5.5 years. A total of 98 pts with high-grade US were identified: 81 leiomyosarcomas and 17 undifferentiated sarcomas. Postoperative chemotherapy was delivered in 53 pts. Median dose of EBRT was 45 Gy in 25 fractions. High-dose rate, low-dose rate, and pulsed-dose rate techniques were used in 66, 31, and 1 pts, respectively. At last follow-up, six pts (6.1%) experienced a locoregional relapse as first event. The International Federation of Gynecology and Obstetrics stage and the tumor size were associated with a higher probability of local relapse. When focusing on pts with stage I-III disease, 5-year overall survival was 77% (95% confidence interval: 67%-87%) and 5-year survival without locoregional failure was 91% (83%-98%). Toxicities were mild to moderate, with only four acute grade 3 toxicities and two grade 3 late effects. CONCLUSION: Vaginal vault BT as part of a multimodal adjuvant treatment was associated with a high locoregional control rate and with acceptable side effects in localized high-grade US. The Oncologist 2017;22:182-188Implications for Practice: This study suggests that an aggressive adjuvant treatment combining chemotherapy and pelvic external beam radiotherapy followed with a brachytherapy of the vaginal vault is associated with a high locoregional control rate and an acceptable toxicity rate in patients with high grade uterine sarcoma. Adding a brachytherapy boost could also allow deescalating the total dose of pelvic external beam radiotherapy, in order to decrease the side effects of adjuvant treatment in these patients without increasing the risk of local relapse. However, the prognosis remains determined by a high frequency of systemic relapses.

Outcome of early stage cervical cancer patients treated according to a radiosurgical approach: Clinical results and prognostic factors.

OBJECTIVE: To report clinical results of a multimodal strategy based on preoperative brachytherapy followed with surgery in early stage cervical cancer. MATERIALS/METHODS: The outcome of consecutive patients receiving brachytherapy in our Institution for an early stage IB1-IIA1 invasive cervical cancer with risk factors (lymphovascular embols and/or tumor >2cm) between 2000 and 2013 was analyzed. The treatment consisted of preoperative low dose or pulse dose-rate utero-vaginal brachytherapy followed, 6-8weeks later, by a radical hysterectomy/bilateral salpingo-oophorectomy plus pelvic±para-aortic lymph node dissection. A postoperative chemoradiation was delivered in patients with histological evidence of lymph nodes metastases. RESULTS: 182 patients were identified. Histological examination of hysterectomy specimen showed the presence of a tumor residuum in 55 patients (30.2%). One patient (0.5%) had residual tumor cells in the parametria. With a median follow-up of 5.3years, 14 patients (7.7%) presented tumor relapse, including three (1.6%) local relapses. Five-year disease-free survival (DFS) rate was 93.6% (95%CI: 91.6-95.6%). In log-rank analysis, presence of pelvic nodal metastases at time of lymphadenectomy (p=0.001) and tumor size ≥3cm (p=0.003) correlated with a poorer DFS. Presence of a tumor residuum on hysterectomy specimen correlated with a higher risk of pelvic or para-aortic failure (p=0.035). A time interval>10weeks between brachytherapy and surgery correlated with a higher risk of failure outside the pelvis (p=0.003). Significant postoperative complications were reported in 16 patients (8.8%). All delayed toxicities were mild to moderate. CONCLUSIONS: A preoperative brachytherapy is a safe and effective option in early stage cervical cancer.

Clinical outcomes of definitive chemoradiation followed by intracavitary pulsed-dose rate image-guided adaptive brachytherapy in locally advanced cervical cancer.

OBJECTIVE: 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). METHODS: 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. RESULTS: 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 D90<80Gy (p=0.018). Eighteen severe late gastrointestinal and urinary effects affecting 14 patients were reported corresponding with a crude incidence of 6.6%. CONCLUSIONS: 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.

Relations of omega-3 and omega-6 intake with mammographic breast density.

PURPOSE: Omega-3 (n-3) and n-6 fatty acids (FA) intake could influence the occurrence of certain diseases such as breast cancer but little is known about their relation to mammographic density (MD). The purpose of this study is to examine the association of the intake of n-3 FA and n-6 FA with MD among 777 premenopausal and 783 postmenopausal women. METHODS: In this cross-sectional study, FA intake was assessed with a self-administered food-frequency questionnaire and MD was measured using a computer-assisted method. Multivariate analyses were performed by using generalized linear models to evaluate the associations of quartiles of FA intake with MD. RESULTS: For increasing quartiles of total long-chain n-3 FA intake (< 0.11, 0.11-0.20, 0.21-0.32, and ≥ 0.33 g/day), adjusted mean MD was 29, 29, 27, and 25 %, respectively (P trend = 0.005). This association remained significant among postmenopausal (P trend = 0.006) but not among premenopausal (P trend = 0.21) women. No significant association was found between n-6 FA intake and MD. However, for increasing quartiles of the n-6 FA/long-chain n-3 FA ratio intake (< 31.75, 31.75-52.28, 52.29-94.28, and ≥ 94.29), adjusted mean MD was 26, 27, 29, and 29 %, respectively (P trend = 0.008). CONCLUSIONS: Higher intake of long-chain n-3 FA was associated with lower MD, suggesting that increased long-chain n-3 FA intake could be a strategy for breast cancer prevention.

Brachytherapy in children with rhabdomyosarcomas of the nasolabial fold.

BACKGROUND: Rhabdomyosarcomas (RMS) of the nasolabial fold can be difficult to manage surgically due to functional and cosmetic limitations. Therefore, brachytherapy (BT) has been proposed to improve local control while limiting the volume of irradiation as well as the extent of the surgical excision. MATERIALS AND METHODS: Sixteen pediatric cases with RMS of the nasolabial fold treated from 1971 to 2005 were retrospectively reviewed. RESULTS: Median follow-up was 4.4 years (1.7-33). Half of the patients were male and their age at diagnosis ranged from 4 months to 13.5 years. Histological subtypes included 10 embryonal and 6 alveolar RMS. Initial treatment consisted of induction multi-agent chemotherapy in all cases. In 12 patients, BT was combined with local excision (4 complete resections, 1 with macroscopic residual disease, and 7 with microscopic disease). Low dose-rate brachytherapy was performed in all cases according to the Paris system, using plastic catheters implanted per-operatively. The doses delivered ranged from 50 to 70 Gy, depending on chemotherapy response, and surgical margin status. 10 patients relapsed: 4 local, 6 regional, and 2 metastatic failures were reported. The median time to relapse was 6.5 months. At the time of analysis eight patients were alive and four had died. Four cases, under palliative care at last check-up, were lost to follow-up. CONCLUSION: BT provided an acceptable local control rate, but the poor regional control of these cases may suggest a need for more aggressive management of cervical regional lymph node regions in RMS of the nasolabial fold.

Consumption of sweet foods and mammographic breast density: a cross-sectional study.

BACKGROUND: The increasing consumption of sugar worldwide seems to lead to several health problems, including some types of cancer. While some studies reported a positive association between sweet foods intake and breast cancer risk, little is known about their relation to mammographic density (MD), a strong breast cancer risk factor. This study examined the association of sweet foods and drinks intake with MD among 776 premenopausal and 779 postmenopausal women recruited at mammography. METHODS: A food-frequency questionnaire was used to assess intake of sweet foods, sugar-sweetened beverages and spoonsful of sugar added. Percent and absolute breast density were estimated using a computer-assisted method. Multivariate generalized linear models were used to evaluate associations. All models were adjusted for potential confounders, including age and body mass index. RESULTS: For increasing quartiles of sugar-sweetened beverages intake, adjusted-mean absolute density was respectively 32, 34, 32 and 36 cm2 among all women (P(trend) = 0.040) and 43, 46, 44 and 51 cm2 among premenopausal women (P(trend) = 0.007). For increasing quartiles of sweet foods intake, adjusted-mean percent density was respectively 16, 16, 17 and 19% among postmenopausal women (P(trend) = 0.036). No association was shown between intake of spoonsful of sugar added and MD. CONCLUSION: Our results suggest that an increase in sweet foods or sugar-sweetened beverage intake is associated with higher MD.

Redefining the role of pulsed-dose-rate brachytherapy in cervical cancer treatment using a preplanned approach.

INTRODUCTION: This study aims to determine predictive factors for cervical cancer patients who would benefit more from high-dose-rate (HDR) or pulsed-dose-rate (PDR) brachytherapy. METHODS: The sample included 50 patients treated with brachytherapy following external radiochemotherapy. PDR plans were compared to HDR preplans, with a focus on patients who may benefit from PDR using preplan metrics and clinical variables. The expected clinical effect was quantified using a tumor control probability model. RESULTS: Results showed PDR plans with 60 pulses to be optimal for achieving target clinical goals for D90CTVHR. A CTVHR volume of >67.5cc and/or D90CTVHR dose on the HDR preplan of <31.1 Gy was the strongest indicator for patient selection who would gain >3% increase in TCP with PDR. The process showed 96% accuracy, 88% sensitivity, and 98% specificity. Only 16% of patients showed a relevant benefit from PDR over HDR, with a mean D90CTVHR of 7 Gy higher and a mean TCP at 3 years of 4.8% higher for PDR. The benefit of PDR is highly influenced by the choice of alpha/beta ratio and repair halftime. CONCLUSION: A small subset of cervical cancer patients may gain from PDR over HDR. CTVHR volume and preplan D90CTVHR doses may be useful in selecting patients for PDR brachytherapy.

Adaptive 3D image-guided brachytherapy: a strong argument in the debate on systematic radical hysterectomy for locally advanced cervical cancer.

PURPOSE: To evaluate the outcomes of patients with locally advanced cervical cancer treated with three-dimensional image-guided brachytherapy (IGABT) after concomitant chemoradiation (CCRT). MATERIALS AND METHODS: Data from patients treated with CCRT followed by magnetic resonance imaging-guided or computed tomography-guided pulsed-dose-rate brachytherapy, performed according to the Groupe Européen de Curiethérapie-European Society for Radiotherapy and Oncology guidelines, were reviewed. At first, stage I or II patients systematically underwent radical hysterectomy or were offered a randomized study evaluating hysterectomy. Then, hysterectomy was limited to salvage treatment. RESULTS: Of 163 patients identified, 27% had stage IB, 57% had stage II, 12% had stage III, and 3% had stage IVA disease. The mean dose delivered (in 2-Gy dose equivalents) to 90% of the high-risk clinical target volume was 78.1 ± 9.6 Gy, whereas the doses delivered to organs at risk were maintained under the usual thresholds. Sixty-one patients underwent a hysterectomy. Macroscopic residual disease was found in 13 cases. With a median follow-up of 36 months (range, 5-79 months), 45 patients had relapsed. The 3-year overall survival rate was 76%. Local and pelvic control rates were 92% and 86%, respectively. According to the Common Toxicity Criteria 3.0, 7.4% of patients experienced late grade 3 or 4 toxicity. Most of those had undergone postradiation radical surgery (2.9% vs. 14.8; p = .005). CONCLUSION: IGABT combined with CCRT provides excellent locoregional control rates with low treatment-related morbidity, justifying the elimination of hysterectomy in the absence of obvious residual disease. Distant metastasis remains an important first relapse and may warrant more aggressive systemic treatment.

SHARE: a French multicenter phase III trial comparing accelerated partial irradiation versus standard or hypofractionated whole breast irradiation in breast cancer patients at low risk of local recurrence.

The standard treatment for breast cancer patients at low risk of recurrence is based on conservative surgery followed by radiation therapy delivered to the whole breast. The accelerated partial breast irradiation (APBI) concept, developed more than 15 years ago, could be an option in selected patients. However, the ideal patient profile for APBI is still not clearly identified. Recent reports from the American Society for Radiation Oncology (ASTRO) and the Groupe Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) have suggested selection criteria for "suitable patients" who could receive APBI outside of clinical trials. Currently, there are 6 ongoing phase III trials. All are characterized by a significant heterogeneity regarding inclusion criteria and stratification factors. The French UNICANCER trial (SHARE; ClinicalTrials.gov identifier NCT01247233) will randomize 2,800 patients in 3 arms: APBI (1 week) using 3-dimensional (3D) conformal radiotherapy, standard radiotherapy (6.5 weeks), and hypofractionated radiotherapy (3 weeks). In this article, we review the reported retrospective studies as well as older randomized trials. We will also describe the differences between the 6 ongoing phase III trials and the particularities of the French SHARE trial.

Survival of clinical stage III NSCLC according to therapeutic strategy: Relevance of the tumor board decision in the era of immunotherapy.

INTRODUCTION: Stage III NSCLC comprises a heterogeneous population. Different treatment strategies are available, including surgery, radiotherapy, and chemotherapy. The PACIFIC trial results represented a significant change and improvement in the therapeutic strategy for these patients. We aimed to compare the different treatment strategies employed in Stage III NSCLC patients within our institution. METHODS: All Stage III NSCLC patients discussed during the weekly thoracic oncology multidisciplinary team meetings at the University hospital Grenoble Alpes (France) between January 2010 and January 2017 were included. Patients' overall survival (OS) according to treatment strategies along with their respective changes were compared. RESULTS: Overall, 476 patients were identified. Among patients initially scheduled to receive neoadjuvant chemotherapy followed by surgery (n = 60), only 37 (62%) actually underwent surgery. Median OS of the cohort was 21.3 months [IQR 25%-75%: 9.6-48.3]. Patients who received neoadjuvant chemotherapy followed by surgery displayed better survival than those treated by CT-RT: 53.2 months [IQR 25%-75%: 16.1-87.3] versus 23.9 [IQR 25%-75%, 13.3-48.1]. Survival was slightly superior for patients treated by upfront CT-RT than for those planned for neoadjuvant chemotherapy followed by surgery who eventually converted to CT-RT (concurrent or sequential): 23.9 months [IQR 25%-75%: 13.3-48.1] versus 20.4 [IQR 25%-75%:10.8-36], respectively. CONCLUSION: While patients who underwent neoadjuvant chemotherapy followed by surgery displayed a better survival than those treated using CT-RT, switch from surgery to CT-RT actually shortened survival. These results stress the relevance of the tumor board in deciding which is the best therapeutic strategy for Stage III disease patients.

Low-dose-rate definitive brachytherapy for high-grade vaginal intraepithelial neoplasia.

BACKGROUND: Treatment of high-grade vaginal intraepithelial neoplasia (VAIN) is controversial and could include surgical excision, topical medication, brachytherapy, or other treatments. We report the results of low-dose-rate (LDR) vaginal brachytherapy for grade 3 VAIN (VAIN-3) over a 25-year period at Gustave Roussy Institute. PATIENTS AND METHODS: We retrospectively reviewed the files of all patients treated at Gustave Roussy Institute for VAIN-3 since 1985. The treatment consisted of LDR brachytherapy using a personalized vaginal mold and delivered 60 Gy to 5 mm below the vaginal mucosa. All patients had at least an annual gynecological examination, including a vaginal smear. RESULTS: Twenty-eight patients were eligible. The median follow-up was 41 months. Seven patients had a follow-up <2 years, and the median follow-up for the remaining 21 patients was 79 months. The median age at brachytherapy was 63 years (range, 38-80 years). Twenty-six patients had a history of VAIN recurring after cervical intraepithelial neoplasia and 24 had a previous hysterectomy. The median brachytherapy duration was 4.5 days. Median doses to the International Commission of Radiation Units and Measurements rectum and bladder points were 68 Gy and 45 Gy, respectively. The median prescription volume (60 Gy) was 74 cm(3). Only one "in field" recurrence occurred, corresponding to a 5- and 10-year local control rate of 93% (95% confidence interval, 70%-99%). The treatment was well tolerated, with no grade 3 or 4 late toxicity and only one grade 2 digestive toxicity. No second cancers were reported. CONCLUSION: LDR brachytherapy is an effective and safe treatment for vaginal intraepithelial neoplasia.

Protoflavonoids from ferns impair centrosomal integrity of tumor cells.

Six protoflavonoids, including two new compounds, were isolated during a large scale screening of fern extracts for original interaction with mitosis. The new compounds isolated from PHEGOPTERIS decursive-pinnata and EQUISETUM fluviatile were 2',3'-dihydroprotogenkwanone (1) and 2',3'-dihydro-2'-hydroxyprotoapigenone (2). Known compounds were: protoapigenone, protogenkwanone, protoapigenin, and 4'- O- ß-D-glucopyranosyl protoapigenin. They showed a cytotoxic activity against HeLa cells at a micromolar level. IC50 values were 2 µM for compound 1 > 10 µM for compound 2, and respectively 2.4, 0.6, > 10 µM for the known compounds. Their cytotoxic effects were associated with phenotypic changes never observed before and characterized by the loss of centrosomal γ-tubulin labelling in both mitotic and interphasic cells.

Image-Guided Brachytherapy for Salvage Reirradiation: A Systematic Review.

BACKGROUND: Local recurrence in gynecological malignancies occurring in a previously irradiated field is a challenging clinical issue. The most frequent curative-intent treatment is salvage surgery. Reirradiation, using three-dimensional image-guided brachytherapy (3D-IGBT), might be a suitable alternative. We reviewed recent literature concerning 3D-IGBT for reirradiation in the context of local recurrences from gynecological malignancies. METHODS: We conducted a large-scale literature research, and 15 original studies, responding to our research criteria, were finally selected. RESULTS: Local control rates ranged from 44% to 71.4% at 2-5 years, and overall survival rates ranged from 39.5% to 78% at 2-5 years. Grade ≥3 toxicities ranged from 1.7% to 50%, with only one study reporting a grade 5 event. Results in terms of outcome and toxicities were highly variable depending on studies. Several studies suggested that local control could be improved with 2 Gy equivalent doses >40 Gy. CONCLUSION: IGBT appears to be a feasible alternative to salvage surgery in inoperable patients or patients refusing surgery, with an acceptable outcome for patients who have no other curative therapeutic options, however at a high cost of long-term grade ≥3 toxicities in some studies. We recommend that patients with local recurrence from gynecologic neoplasm occurring in previously irradiated fields should be referred to highly experienced expert centers. Centralization of data and large-scale multicentric international prospective trials are warranted. Efforts should be made to improve local control while limiting the risk of toxicities.

Study protocol to assess polypharmacy and comorbidities in lung cancer.

BACKGROUND: At least half of patients with lung cancer have comorbidities, which can affect treatment decisions and survival. Associated with comorbidity, polypharmacy can also have consequences on patient care. This study will evaluate both polypharmacy and comorbidities in a cohort of hospitalized patients on the administration of chemotherapy and survival. METHODS: In this monocentric retrospective study, patients diagnosed with lung cancer during their first hospitalization in thoracic oncology were included between 2011 and 2015. Four datasets were obtained containing the variables of interest. Deterministic data linkage will be performed. The main objective will be to assess the impact of polypharmacy and comorbidities on chemotherapy administration within two months after the first hospitalization in thoracic oncology. The probability of chemotherapy administration will be estimated using the Kaplan Meier method. Prognostic factors will be identified using a Cox model. The Fine and Gray method will be used to analyze the competitive risk of death. EXPECTED RESULTS: We first aim to demonstrate the feasibility of working with real-life data and aggregate different databases. Then our goal is to assess impact of polypharmacy and comorbidities on chemotherapy administration and on the survival of lung cancer patients. This would help to understand the possibilities to aggregate several database for a protocol in view to help clinicians to rationalize treatment and define inappropriate medications for this population.

Pulsed Dose Rate Brachytherapy of Lip Carcinoma: Clinical Outcome and Quality of Life Analysis.

PURPOSE: Lip carcinoma represents one of the most common types of head and neck cancer. Brachytherapy is a highly effective therapeutic option for all stages of lip cancers. We report our experience of pulsed dose rate brachytherapy (PDR) as treatment of lip carcinoma. METHODS AND MATERIALS: this retrospective single center study included all consecutive patients treated for a lip PDR brachytherapy in our institution from 2010 to 2019. The toxicities and outcomes of the patients were reported, and a retrospective quality of life assessment was conducted by phone interviews (FACT H&N). RESULTS: From October 2010 to December 2019, 38 patients were treated in our institution for a lip carcinoma by PDR brachytherapy. The median age was 73, and the majority of patients presented T1-T2 tumors (79%). The median total dose was 70.14 Gy (range: 60-85 Gy). With a mean follow-up of 35.4 months, two patients (5.6%) presented local failure, and seven patients (19%) had lymph node progression. The Kaplan-Meier estimated probability of local failure was 7.2% (95% CI: 0.84-1) at two and four years. All patients encountered radiomucitis grade II or higher. The rate of late toxicities was low: three patients (8.3%) had grade II fibrosis, and one patient had grade II chronic pain. All patients would highly recommend the treatment. The median FACT H&N total score was 127 out of 148, and the median FACT H&N Trial Outcome Index was 84. CONCLUSIONS: This study confirms that an excellent local control rate is achieved with PDR brachytherapy as treatment of lip carcinoma, with very limited late side effects and satisfactory functional outcomes. A multimodal approach should help to improve regional control.

Analysis of Radiation Dose/Volume Effect Relationship for Anorectal Morbidity in Children Treated for Pelvic Malignancies.

PURPOSE: To examine dose-volume effect relationships for anorectal morbidity in children treated with image-guided brachytherapy for pelvic tumors. METHODS AND MATERIALS: Medical records of all consecutive children with pelvic tumors treated in our center and receiving image-guided pulsed-dose-rate brachytherapy with or without external beam radiation therapy (EBRT) between 2005 and 2019 were reviewed. The effect of the minimal doses to the most exposed 0.5 cm3, 1 cm3, and 2 cm3 of the anorectum (respectively: D0.5cm3, D1cm3, and D2cm3), total reference air kerma (TRAK), and volume of 100% isodose was examined for anorectal toxicities. RESULTS: Seventy-eight consecutive children were included. Median age was 2.9 years (range, 0.8-14.9 years). Most of the tumors were bladder or prostate (67%) or vaginal (22%) rhabdomyosarcoma. Six patients received EBRT in addition to brachytherapy. Median follow-up was 21.3 months. At last follow-up, 30 children (38%) had experienced Common Terminology Criteria for Adverse Events version 5 grade ≥1 acute or late anorectal events: 24% had grade 1 events, 7.7% had grade 2 events, and 6.4% had grade 3 events. No toxicity greater than grade 3 was observed (eg, fistula or stricture). In univariate analysis, the D0.5cm3 and D1cm3 were significant for probability of grade 1 to 3 (P = .009 and P = .017, respectively) and grade 2 to 3 anorectal morbidity (P = .007 and P = .049, respectively). There was no significant correlation for D2cm3 (P = .057 for grade 1-3; P = .407 for grade 2-3). A 10% probability (95% confidence interval, 4%-20%) for anorectal toxicity of grade 2 or greater was reached for a D0.5cm3 = 52 Gy. The age, EBRT use, TRAK, and treated volume values were not significant. CONCLUSIONS: To our knowledge, this study is the first to show a significant dose-volume effect relationships for anorectal morbidity in children undergoing treatment with brachytherapy. Integrating these data into brachytherapy treatment planning could help to optimize the therapeutic index in these young patients.