Shared Decision Making in Oncology and Its Implementation in Cervical Cancer Management in the Philippines: A Narrative Review.

PURPOSE: Shared decision making (SDM) is an approach where clinicians and patients make decisions together using the best available evidence. Although much studied, recognized to be ethically imperative, and recommended in international health policies, it remains poorly implemented. In the Philippines, there are limited studies on patient decision making preferences and SDM. Practical guidance on the implementation of SDM or use of patient decision aids (PtDAs) is often not detailed in existing national clinical practice guidelines in oncology. METHODS: We performed a systematic search of Philippine literature on SDM in oncology and an iterative review of international literature on the philosophy and methods of SDM, the utility and effectiveness of PtDAs, and the facilitators and barriers to implementation or usage. We contextualized our review to the cervical cancer management and health service delivery in the Philippines. RESULTS: Local literature is limited to five scientific publications and two registered studies. International literature encompasses patient decisional preferences, the role of PtDAs and the standards for their development and evaluation, their effectiveness, and barriers and facilitators to their use in cancer-related decision making. We discussed the implications on the management of cervical cancer in the Philippines, challenges in health service delivery and standards, and SDM research. CONCLUSION: Local SDM research is limited. Our preliminary experience in a multicenter clinical trial in Manila on PtDA use in the framework of SDM in cervical cancer suggest good patient and clinician acceptability. Challenges to implementation such as unfavorable financial situations, urgency of clinical decisions, low patient or caregiver educational attainment, and poor integration of multidisciplinary and SDM in organizational workflows will be important when implementing SDM in different settings.

Challenges and opportunities in the implementation of advanced brachytherapy programs for cervical cancer in the Philippines.

Cervical cancer is the second most common cancer cause of morbidity and mortality in Filipino women; the age-standardized annual incidence is 15.2 as of March 2023. The majority are diagnosed at a locally advanced stage and in the reproductive and working age group. This results in important treatment and productivity costs. The importance of image-guided and interstitial brachytherapy (BRT) in local control and toxicity outcomes has been shown in recent meta-analyses. We review the status of advanced BRT program training and implementation in the Philippines and important challenges and opportunities to move forward.

Patient Decision Aid for Chemotherapy or Exclusion in Cisplatin-Intolerant Patients With Locally Advanced Cervical Cancer: Development, Alpha Testing, and Peer Validation.

PURPOSE: In locally advanced cervical cancer (LACC), adding cisplatin to radiotherapy (RT) improves survival but increases toxicity. Among patients with cisplatin contraindications, RT compliance may be compromised by toxicity because of cisplatin or a substitute. In shared decision making, a patient decision aid (PtDA) may decrease decisional conflict and attitudinal barriers, thereby improving treatment compliance. METHODS: Following International Patient Decision Aid Standards (IPDAS) guidelines, a steering committee of two radiation oncologists, a gynecologic oncologist, an oncology nurse, a clinical psychologist, a cancer survivor, and a caregiver developed the chemotherapy or exclusion in cisplatin-intolerant patients with LACC (CECIL) prototype, a PtDA for cisplatin-intolerant patients with LACC deciding about adding chemotherapy to RT. The prototype was alpha-tested using the e-Delphi method. The patient decision aid research group Ottawa Acceptability Questionnaire was used to evaluate comprehensibility, length, amount of information, neutrality, and overall suitability for decision making. The prototype was then independently evaluated by local internal, local external, and international reviewers using the IPDAS checklist version 4, which encompasses information, probabilities, values, guidance, development, evidence, disclosure, plain language, and evaluation. RESULTS: Alpha testing showed high practitioner acceptability (all items with mean and median scores ≥4; overall mean score 4.70 of 5.00) and good patient acceptability (all items rated good to excellent). Content validation showed that the PtDA satisfied all IPDAS six qualifying and six certification criteria, with high overall mean score (3.63 of 4.00) for all 17 applicable quality criteria. CONCLUSION: The CECIL prototype shows good practitioner and patient acceptability, and content validity on peer review. Clinical testing to determine its effectiveness in reducing decisional conflict is ongoing.

Teleconsultation Perceptions of Medical and Radiation Oncologists in the COVID-19 and Post-COVID-19 Era: A National Survey in the Philippines.

PURPOSE: The study reports on the current perception of medical and radiation oncologists regarding teleconsultation in the Philippines. Before the COVID-19 pandemic, the adoption of telemedicine was not widespread. With movement restrictions imposed during the pandemic, physicians were compelled to use telemedicine. It is uncertain whether physicians will still adopt its use in practice in the post-COVID-19 era. This study gives insight into the possible adaptation of this mode of consultation in the future, especially in areas with limited health care resources. MATERIALS AND METHODS: We conducted a national survey among medical oncologists and radiation oncologists in the Philippines. A 43-item online survey was developed, validated, and administered to the oncologists. The demographics and data from categorical questions were reported as frequencies and percentages. RESULTS: A total of 142 responses were gathered from 82 medical oncologists and 60 radiation oncologists. There was agreement among participants that, during the pandemic, teleconsultation could be used for the first visit, diagnostic workup request, treatment explanation, follow-up care, and chronic disease management. There was disagreement whether cancer diagnosis disclosure and cancer prognosis revelation could be performed via teleconsultation, and there was agreement that emergency consultation and physical examination would warrant a face-to-face consultation. After the COVID-19 pandemic, 78.7% intend to continue using teleconsultation except for emergency consultations, first visits, physical examination, diagnosis disclosure, and cancer prognosis revelation. CONCLUSION: Teleconsultation was perceived by oncologists as an acceptable method of providing cancer care during and after the COVID-19 pandemic. Oncologists also intend to use teleconsultation in the post-COVID-19 era in certain aspects of patient care.

Technical details and clinical outcomes after high-dose-rate intracavitary brachytherapy for squamous cell carcinoma of external auditory canal and external beam radiotherapy for nodal coverage: A case report.

Purpose: To report technical details and 15-month outcomes of a patient with node-positive external auditory canal (EAC) squamous cell carcinoma (SCC) treated with definitive intracavitary high-dose-rate (HDR) brachytherapy to primary tumor, and external beam radiotherapy (EBRT) to draining lymphatics. Material and methods: A 21-year-old male was diagnosed with SCC of the right EAC. The patient underwent definitive HDR intracavitary brachytherapy, 340 cGy/fraction for 14 twice-daily fractions, followed by EBRT using intensity-modulated radiation therapy (IMRT) to cover the grossly enlarged pre-auricular node, ipsilateral intra-parotid, and cervical lymph node levels II and III. Results: The approved brachytherapy plan had an average high-risk clinical tumor volume (CTV-HR) D90 of 341 cGy with a total dose of 47.7 Gy (BED, 80.3 Gy, EQD2, 66.6 Gy). For the approved IMRT plan, the prescription to the involved right pre-auricular node was 66 Gy in 33 fractions, and more than 95% of the target received at least 62.7 Gy. High-risk nodal regions were simultaneously prescribed: 59.4 Gy in 1.8 Gy fractions, and more than 95% received at least 56.4 Gy. Organs at risk (OARs) were kept below their dose constraints.The patient tolerated both the procedures with no grade ≥ 2 treatment-related adverse events. Grade 1 dermatitis in the right pre-auricular and cervical areas during the course of EBRT was experienced. Fifteen months post-RT, the patient has no evidence of disease, and was noted to have EAC stenosis, which translated to moderate conductive hearing loss of the right ear. Thyroid function was normal at 15 months after EBRT. Conclusions: This case report illustrates that the delivered definitive radiotherapy is technically feasible, effective, and well-tolerated in patients with SCC of EAC.

Development and pilot-testing of the expanded prostate index composite - Filipino version (EPIC-F).

INTRODUCTION: Quality-of-life (QOL) is paramount in clinical decision-making in the management of prostate cancer patients. The expanded prostate index composite (EPIC) is a widely used and well-validated QOL tool that allows for the evaluation of bowel, urinary, sexual, and hormonal domains. A Filipino translation was previously lacking. We describe the development and pilot testing of the Filipino translation of the EPIC (EPIC-F). METHODOLOGY: The EPIC-32 was translated into Filipino using iterative forward and backward procedures with checks for semantic congruency. The translation was then evaluated by an expert panel consisting of a prostate cancer survivor and pertinent health professionals. A focused group discussion (FGD) was conducted to explore sources of difficulty of use to guide improvement. RESULTS: The linguistically validated translation was evaluated to have cultural relevancy, adequacy, and representativeness by the expert panel, and to have good understandability and answerability by a representative pilot cohort of prostate cancer patients. Seven unsatisfactory items were identified, all pertaining to the sexual domain, and required minimal revision on review during the FGD. CONCLUSION: The EPIC-F is a linguistically and culturally validated version of the EPIC 32, with good understandability and answerability, permitting clinical use. Its psychometric properties need to be determined to define its utility in clinical research.

Simple fabrication technique of personalized endocavitary brachytherapy applicator for maxillary alveolar cancer.

Purpose: We report on methods and outcomes of post-operative endocavitary brachytherapy after prior irradiation and salvage surgery in a patient with maxillary alveolar squamous cell carcinoma (SCC). Material and methods: A 67-year-old male with right maxillary alveolar SCC was referred for brachytherapy after prior definitive chemoradiotherapy and salvage posterior maxillectomy. A personalized endocavitary applicator was fabricated using dental impression plastic tray, vinyl polysiloxane paste, and four flexible catheters to deliver fourteen 3.5 Gy high-dose-rate fractions. High-risk and intermediate-risk clinical target volumes were treated to 3.7 Gy (D90) and 2.4 Gy (D98), with mandibular dose limited to 2.3 Gy (D2cc) per fraction. These corresponded to total 2 Gy equivalent doses (EQD2) of 72.8 Gy, 40.5 Gy, and 34 Gy, respectively. Results: The patient developed grade 2 mucositis and was disease-free for six months. He had biopsy-confirmed local recurrence at 8 months. He refused further treatment and expired within a month. Conclusions: This simple approach to a personalized endocavitary applicator is feasible and allows for lower costs and less treatment delays, while ensuring patient comfort and convenience.

Clinical outcomes of single application multi-fractionated CT-guided interstitial high-dose-rate brachytherapy for locally advanced cervical cancer: A multi-institution initial experience.

Purpose: The aim of the study was to evaluate the safety and clinical outcomes of single application multi-fractionated computed tomography (CT)-guided interstitial high-dose-rate brachytherapy given in four fractions in locally advanced cervical cancer. Material and methods: Patients with locally advanced cervical cancer stage IIB-IVA treated definitively with external radiation ± weekly cisplatin, followed by single application multi-fractionated CT-guided interstitial high-dose-rate brachytherapy in four fractions were included. Dosimetry data, clinical response, and toxicity records were reviewed. Results: Between January 2018 and December 2022, twenty-two patients were included. Clinical stage distribution was as follows: IIB - 13.6%, IIIB - 27.3%, IIIC - 22.7%, and IVA - 36.4%. Mean high-risk clinical target volume (HR-CTV) was 66.19 ±32.69 cm3, and HR-CTV D90 dose was 86.8 ±1.7 Gy. 2 cc doses to bladder, rectum, and sigmoid were 84.6 ±2.8 Gy, 71.5 ±2.4 Gy, and 65.6 ±4.0 Gy, respectively. Mean overall treatment time was 66 ±21 days. With a median follow-up of 11.5 months (range, 5-44 months), median survival and local control were not achieved. One-year local control rate, one-year progression-free survival, and one-year overall survival were 82%, 66%, and 78%, respectively. Univariate analysis showed overall treatment time to be the only variable associated with all oncologic outcomes. For acute toxicity, grade 3 toxicity in four patients and grade 4 toxicity of infection in one patient were observed. For late toxicity, grade 3 gastrointestinal toxicity was noted in two patients. Conclusions: Initial results suggest that single application multi-fractionated CT-guided interstitial brachytherapy given in four fractions in locally advanced cervical cancer seems to be feasible and safe, but additional evidence is needed to generate more validated conclusions.

Outcomes with definitive radiotherapy among patients with locally advanced cervical cancer with relative or absolute contraindications to cisplatin: A systematic review and meta-analysis.

BACKGROUND: The standard treatment for locally advanced cervical cancer (LACC) is chemoradiation (CRT) with cisplatin, followed by brachytherapy, but is less defined for cisplatin-intolerant patients. We synthesized evidence on treatment outcomes with definitive radiotherapy (RT) with or without chemotherapy (ChT) in these patients. METHODS: We performed a systematic search and included 20 relevant studies. We extracted data on response, survival, compliance, and toxicity, and performed meta-analyses of outcome rates and risk ratios. Sensitivity and subgroup analyses were performed to explore sources of heterogeneity. Meta-regression was performed to examine the effects of other variables. RESULTS: Due to lack of comparative data, most comparisons were indirect and derived from the proportional meta-analyses. Complete response (85%) and survival (62% 5yOS) rates are comparable to those published for LACC without contraindications to cisplatin. Survival rate is better with CRT than RT alone (5yOS, 73% vs 58%), and with nodal boost (NB) than without (5yOS, 71% vs 56%). Carboplatin CRT is associated with lower 5yOS (44%) but better ChT compliance (86%) when compared to other interventions. ChT compliance is better in renal failure than elderly cohorts (89% vs 67%). RT compliance is lower with CRT than RT alone (90% vs 96%), and higher with NB than none (96% vs 93%). NB is associated with lower RT compliance than no NB, when ChT is given. Meta-regression results affirm ChT and NB to be significant positive factors for survival, and NB, which is associated with greater use of advanced RT techniques, for RT compliance. CONCLUSION: For those with relative contraindications, cisplatin CRT is effective and well-tolerated. For those with absolute contraindications, carboplatin is well-tolerated but with unclear effectiveness. Nodal boost is effective and well-tolerated, but is less tolerated when concurrent ChT is given.

Phase 1/2 trial evaluating the effectiveness and safety of dose-adapted Hypofractionated pelvic radiotherapy for Advanced Cervical cancers INeligible for ChemoTherapy (HYACINCT).

BACKGROUND: The standard treatment for locally advanced cervical cancer (LACC) is concurrent chemoradiation (CRT) followed by brachytherapy (BRT). The addition of chemotherapy (ChT) to radiotherapy (RT) is associated with a 7.5% improvement in overall survival but with more grade 3-4 acute toxicities (16.4% vs 4.9%, CRT vs RT alone). The risk-benefit ratio could be less favorable in advanced disease with renal dysfunction secondary to tumor-related hydronephrosis; borderline cardiac function; and frail patients. RT alone followed by BRT achieves long-term locoregional control <62%. Hypofractionated RT (HF-RT) using older techniques result in comparable disease control and low late toxicity rates (4-8%). Dose-adapted HF-RT using intensity-modulated RT with nodal simultaneous integrated boost (nSIB) could improve tumor control and toxicity, when ChT is contraindicated. METHODS: The HYACINCT study is a two-phase study to determine the effectiveness and safety of HF-RT with nSIB in LACC when ChT is contraindicated. Phase 1 is a dose-escalation study using standard 3 + 3 design, to determine the maximum tolerated dose (MTD) for nSIB in combination with pelvic HF-RT (2.67 Gy x 15 fractions). Phase 2 is a single-arm clinical trial using Simon's two-stage design, to assess the efficacy of HF-RT with nSIB in terms of tumor response. Adult women with biopsy-proven, untreated LACC, with contraindication to ChT will be included in this trial. DISCUSSION: For the phase 1, the primary endpoint is dose-limiting toxicity (DLT), or any grade ?3 acute or sub-acute toxicity. The dose level at which incidence of DLT is ?33% is defined as the maximum tolerance dose (MTD). For the phase 2, the primary endpoint is complete response at 3 months post-treatment. Secondary outcomes are progression-free and overall survival, acute and late toxicity, and patient-reported outcomes (EPIC, EORTCQLQ C30 + CX24, PGIC, PCIS). Trial registration: NCT05210270.

Chemoradiotherapy in a patient with locally advanced small cell neuroendocrine carcinoma of the cervix complicated by pelvic organ prolapse: A case report.

BACKGROUND: The coexistence of cervical cancer and pelvic organ prolapse represents a rare clinical scenario. Small cell neuroendocrine histology likewise represents only 0.9-1.5% of all invasive cervical cancers. There is no consensus regarding the optimal management of patients with concomitant locally advanced cervical cancer and pelvic organ prolapse. CASE SUMMARY: The patient was a 32-year old woman with an 8-cm fungating cervical mass extruding from the introitus. Biopsy was consistent with small cell neuroendocrine carcinoma. Examination showed stage IIIC1r cervical cancer with stage IV pelvic organ prolapse. After manual reduction, a pessary was used to optimize target volume reproducibility during definitive chemoradiation. The patient was treated using cisplatin and etoposide chemotherapy with intensity modulated radiation therapy followed by intracavitary brachytherapy. The patient had no clinical evidence of disease and recurrence of symptomatic prolapse one year after treatment completion. CONCLUSION: This is the first reported case of a cervical neuroendocrine carcinoma in a prolapsed uterus, and the youngest patient in literature to have concomitant cervical cancer and pelvic organ prolapse. The use of a pessary for optimizing target volume reproducibility during definitive chemoradiation is a viable option in managing this rare case scenario.

A systematic review of the barriers to implementing human papillomavirus vaccination programs in low- and middle-income countries in the Asia-Pacific.

AIM: The increasing burden of human papillomavirus (HPV)-related diseases in low- and middle-income countries (LMICs) could be alleviated by effective HPV vaccination programs. In this systematic review, we examined barriers to introduction, implementation, and/or sustainability of HPV vaccination programs in LMICs in the Asia-Pacific region (AP-LMICs). METHODS: A systematic search of literature from the past 10 years (2010-2019) was performed through PubMed, Cochrane CENTRAL, and Google Scholar. Studies were included if they reported barriers to HPV vaccination in AP-LMICs. All study designs were included except commentaries and editorials. The journal articles were assessed using the Joanna Briggs Institute critical appraisal checklists. RESULTS: A total of 46 eligible articles were included. An increase in publications was noted from 2010 to 2019. Barriers were diverse and were classified into four levels--government, healthcare providers (HCPs), society, and individual. The top specific barriers that were identified across AP-LMICs are lack of funding and political support at the government level, lack of awareness among HCP and lack of vaccination programs at the level of health providers, and the perceived cost/benefit ratio for the individual level. CONCLUSION: Barriers to successful implementation of HPV vaccination programs differ among Asia-Pacific LMICs. Policymakers will need to evaluate the relative importance of these barriers in their target areas and population in order to draft an effective dissemination and implementation strategy.

Orbital mold brachytherapy for recurrent orbital mesenchymal chondrosarcoma: a case report.

PURPOSE: The aim of this case report is to present a case of orbital mesenchymal chondrosarcoma sarcoma with multiple recurrences, and to report technical details of a contemporary approach for orbital brachytherapy that can be used in low-resource settings. MATERIAL AND METHODS: A 46-year-old female diagnosed with recurrent orbital mesenchymal chondrosarcoma of the left orbit presented with her third local recurrence. The patient proceeded with conservative surgery with planned adjuvant high-dose-rate brachytherapy 2 weeks post-surgery. Brachytherapy mold applicator was fabricated using thermoplastic mask, ProGuide catheter needles, catheter fixation buttons, and a strip of gauze. Ideal catheter placement was done with CT simulation planning. RESULTS: High-risk clinical target volume (HR-CTV) corresponded to gross tumor residual, and intermediate-risk clinical target volume (IR-CTV) corresponded to the whole orbit. Flexitron iridium-192 high-dose-rate (HDR) brachytherapy plan was generated using Oncentra brachytherapy planning system. The treatment plan had HR-CTV total dose of 55.6 Gy and equivalent dose in 2 Gray fractions (EQD2) of 96 Gy. IR-CTV total dose was 45.5 Gy and EQD2 of 70 Gy. The plan was evaluated using dose-volume histogram and dosimetric parameters, which showed adequate irradiation of tumor volume and at-risk areas. The patient underwent orbital brachytherapy without any adverse events, except for mild skin erythema. One-year post-treatment showed no local recurrence and no soft tissue necrosis or swelling. CONCLUSIONS: In the previously irradiated orbital sarcoma patient, adjuvant brachytherapy is an effective and safe modality for the delivery of sufficient radiation dose to the target, as presented in the current case report. The materials used in the brachytherapy applicator are easily available in majority of radiation therapy centers and can be manufactured even in low-resource settings.

Assessing the Effect of Radiotherapy in Addition to Surgery in Colon Adenocarcinomas: a Systematic Review and Meta-analysis of Contemporary Evidence.

PURPOSE: This study aims to review the contemporary evidence investigating radiotherapy (RT) in addition to surgery for colon adenocarcinomas. METHODS: We searched the following databases: PubMed, Science Direct, Scopus, ASCOpubs, the Cochrane Library, and Google Scholar. Studies (since January 2005) comparing outcomes of high-risk colon adenocarcinomas who underwent RT in addition to surgery versus no RT were eligible. Pooling of outcomes from published results or from analysis of survival curves was done. Subgroup analysis was conducted to determine if the efficacy of RT varies with RT timing. RESULTS: Eight studies were included (five retrospective cohorts, three population-based studies). Pooled analysis from retrospective cohorts showed a reduction in 5-year LR (OR 0.41; 95% CI 0.21-0.79; p = 0.007) in the RT group. A benefit in 3-year (OR 1.81; 95% CI 1.15-2.87; p = 0.01) and 5-year (OR 2.10; 95% CI 1.21-3.63; p = 0.008) DFS and in 3-year (OR 2.55; 95% CI 1.43-4.54; p = 0.001) and 5-year (OR 2.00; 95% CI 1.17-3.41; p = 0.01) OS was seen in the RT group. The OS benefit was demonstrated in the subgroup analysis of neoadjuvant RT, but not with adjuvant RT. The improvement in OS with neoadjuvant RT was supported by a population-based study from NCDB, while results from two population-based studies investigating adjuvant RT were conflicting. CONCLUSION: Taking into account the limitations of the studies, our review of evidence suggests a possible role of RT in improving oncologic outcomes of select colon adenocarcinomas. Prospective studies are needed to definitively assess the value of RT for colon cancer.

Reirradiation for Recurrent Nasopharyngeal Carcinomas: Experience From an Academic Tertiary Center in a Low- to Middle-Income Country.

PURPOSE: The objectives of this study were to report the oncologic outcomes and the treatment-related toxicities after reirradiation (re-RT) for recurrent nasopharyngeal carcinoma (rNPC) at our institution and to apply a recently published prognostic model for survival in rNPC in our cohort. PATIENTS AND METHODS: Thirty-two patients with rNPC treated at the authors' institution with re-RT were retrospectively reviewed. Treatment modalities for re-RT were intensity-modulated radiotherapy (n = 14), three-dimensional conformal radiotherapy (n = 9), single-fraction stereotactic radiosurgery (n = 6), fractionated stereotactic radiotherapy (n = 2), and high dose rate intracavitary brachytherapy (n = 1). Twenty-seven patients received re-RT with curative intent, whereas five patients were treated palliatively. RESULTS: Median follow-up time was 15.5 months (range, 1 to 123 months) for the entire cohort and 20 months (range, 3 to 123 months) for patients treated with curative intent. For the entire cohort, median locoregional recurrence-free survival (LRRFS) was 14 months, with actuarial 1- and 2-year LRRFS estimates of 67.5% and 44.0%, respectively. Median overall survival (OS) time was 38 months, with actuarial 1- and 2-year estimates of 74.2% and 57.2%, respectively. For patients treated with curative intent, median LRRFS was not reached. Actuarial 1- and 2-year LRRFS estimates were 68.2% and 54.5%, respectively. Median OS time after curative intent re-RT was 42 months, with actuarial 1- and 2-year estimates of 75.4% and 63.8%, respectively. One- and 2-year OS estimates based on risk stratification were 68.6% for high risk compared with 80.8% for low risk and 34.3% for high risk compared with 70.7% for low risk, respectively ( P = .223). Three patients (9.4%) developed symptomatic temporal lobe necrosis. There was no reported grade 5 treatment-related toxicity. CONCLUSION: Results of the study suggest that re-RT is an effective and safe salvage treatment strategy for rNPC. Re-RT to a maximum equivalent dose in 2-Gy fractions of 60 Gy may yield good LRRFS and translate to prolonged OS.

Neoadjuvant Radiotherapy Versus No Radiotherapy for Stage IV Rectal Cancer: a Systematic Review and Meta-analysis.

PURPOSE: The aim of this study is to review the contemporary evidence comparing neoadjuvant radiotherapy (NRT) versus no radiotherapy (no RT) in patients with stage IV rectal cancer. METHODS: Literature was searched for studies using the following databases: Pubmed, EMBASE, Science Direct, Scopus, ASCOpubs, the Cochrane Library, and Google Scholar. Studies reporting outcomes for stage IV rectal cancer patients who underwent NRT or no RT were selected. RESULTS: A total of eight studies were included in this review (one RCT, five retrospective cohorts, two population-based studies). The only RCT in this review reported no significant difference in 2- and 5-year local recurrence (NRT versus no RT) 10.1% versus 23.8%, and 15.9% versus 26.9%, respectively. However, multivariate analysis showed the effect of treatment might not have differed between subgroups according to stage. Pooled analysis from five retrospective studies showed significantly improved local recurrence-free survival (LRFS) with NRT (risk ratio [RR] 1.15; 95% CI 1.01-1.31, p = 0.03), which was maintained in the subgroup who underwent metastasectomy. (RR 1.18; 95% CI 1.01-1.37, p = 0.04). Pooled 5-year overall survival (OS) showed a statistically significant benefit with NRT (RR 1.47; 95% CI 1.14-1.89, p = 0.003), which was not seen in the subgroup who underwent metastasectomy (RR 1.31; 95% CI 0.94-1.82, p = 0.11). CONCLUSION: The current available evidence shows an LRFS benefit with NRT over no RT in patients with stage IV rectal cancer. The review also suggests a possible OS benefit with NRT, although this finding should be interpreted with caution.

A novel applicator design for intracavitary brachytherapy of the nasopharynx: Simulated reconstruction, image-guided adaptive brachytherapy planning, and dosimetry.

PURPOSE: In nasopharyngeal cancer, brachytherapy is given as boost in primary treatment or as salvage for recurrent or persistent disease. The Rotterdam nasopharyngeal applicator (RNA) allows for suboptimal reduction of soft palate radiation dose, based on image-guided brachytherapy plans. Building on the RNA, we propose a novel design, the Benavides nasopharyngeal applicator (BNA). METHODS AND MATERIALS: The virtual BNA was reconstructed on two cases (one T1, one T2) previously treated with intracavitary brachytherapy using the RNA. Dose was prescribed to the high-risk clinical target volumes (CTVs) and optimization was such that high-risk CTV D90 ≥ 100% of prescribed dose (PD), intermediate-risk-CTV D90 ≥ 75% PD, and soft palate D2cc ≤ 120% PD. The optimized RNA and BNA image-guided brachytherapy plans were compared in terms of CTV coverage and organs-at-risk sparing. RESULTS: Optimization objectives were more easily met with the BNA. For the T1 case, all three planning objectives were easily achieved in both the RNA and BNA, but with 18-19% lower soft palate doses with the BNA. For the T2 case, the CTV planning objectives were achieved in both the RNA and BNA, but the soft palate constraint was only achieved with the BNA, with 38-41% lower soft palate doses. CONCLUSIONS: Compared to the RNA, the BNA permits easier optimization and improves therapeutic ratio by a significant reduction of soft palate doses, based on simulation using a proposed system for CTV/organs-at-risk delineation, prescription, and optimization for image-guided adaptive brachytherapy. Clinical piloting using a prototype is necessary to evaluate its feasibility and utility.

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.

Pulsed-dose rate brachytherapy for pediatric bladder prostate rhabdomyosarcoma: Compliance and early clinical results.

OBJECTIVE: No data are available on the feasibility of pulsed dose rate (PDR) brachytherapy in very young children. Our experience of PDR brachytherapy for bladder prostate (BP) rhabdomyosarcoma (RMS) is reported, with focus on compliance and dosimetric parameters. MATERIALS AND METHODS: Treatment parameters and outcome of consecutive BP RMS patients treated in our center were examined. Treatment was carried out as part of a multimodal conservative radio-surgical treatment. Four single leader plastic tubes were implanted under perioperative guidance, encompassing the prostate/bladder neck. Tubes were systematically sutured to the bladder wall. Treatment planning was based on a computed tomography and followed Paris system rules. Continuous hourly pulses of 0.42Gy were delivered, to a total dose of 60Gy. RESULTS: 32 patients were treated, median age 2.6years (10months-12years). Median duration of each pulse was 8.5min (3.8-17.4min). The minimal dose in the most irradiated 1cm3 of rectum was 44.7Gyα/ß=3 (range: 4.1-77.3Gyα/ß=3). Brachytherapy was conducted without significant compliance concern in all but two patients, 24 and 25months-old, who pulled out plastic tubes before treatment completion. Another child needed re-planning because of slight tube displacement. With median follow-up of 14.4months (15days-75months), all patients were free from any relapse after local treatment. Four grade 3 acute urinary complications were encountered. All long-term side effects were grade 2 or less. CONCLUSION: PDR brachytherapy is feasible in very young patients, and associated with acceptable acute toxicity rates. Longer follow-up is required to ensure that local control and long-term side effects profile are comparable to the results of low dose rate brachytherapy.

Clinical outcomes after interstitial brachytherapy for early-stage nasal squamous cell carcinoma.

PURPOSE: Radiotherapy of nasal carcinomas results in cure rates comparable to surgery, with anatomic preservation and good cosmesis. Brachytherapy (BT) overcomes difficulties with dosimetric coverage and affords a localized and highly conformal irradiation. We report our experience of BT for early-stage nasal squamous cell carcinomas (SCCs). METHODS AND MATERIALS: Clinical data, BT parameters, and outcome of consecutive patients treated by interstitial BT in our institute between December 1982 and April 2015 for a localized nasal SCC were examined. A total of 34 patients with newly diagnosed T1-2N0-1 nasal skin (n = 22) or nasal cavity (n = 12) SCC were identified. Implantation and dosimetry were done according to the Paris system rules. Low-dose-rate (n = 30) or pulsed-dose-rate (n = 4) techniques were used. Median dose was 70 Gy (64-75 Gy). Sites of tumor recurrence, toxicity rates, and cosmesis outcome were examined. RESULTS: Median followup time was 89 months. All patients achieved complete response. Five patients experienced local failure, with a median interval of 9 months (range, 5-12 months). Grade 3 acute reactions were reported in 2 patients (6%). Most delayed complications were mild to moderate, and good or fair cosmesis was achieved in 97%. Estimated local failure-free survival and disease-free survival rates at 5 year were 85% (95% CI = 68-94%) and 76% (95% CI = 58-88%), respectively. CONCLUSIONS: Interstitial BT is effective for selected nasal SCCs, with durable local control, acceptable toxicity, and good cosmesis.