Lucas C. Mendez

Pattern of relapse and dose received by the recurrent intraprostatic nodule in low- to intermediate-risk prostate cancer treated with single fraction 19 Gy high-dose-rate brachytherapy

PURPOSEnThe purposes of this study were to investigate the pattern of relapse in patients with low- or intermediate-risk prostate cancer treated with 19-Gy high-dose-rate brachytherapy (HDR-BT) and to calculate the dose received by the area of recurrence.nnnMETHODS AND MATERIALSnPatients included in this analysis were treated under a Phase II randomized trial that evaluated the role of 19-Gy HDR-BT monotherapy in low- and intermediate-risk prostate cancers. Multiparametric prostate MRI and prostate biopsy were performed in patients with suspicious local recurrence. The site of local relapse was compared with the initial site of disease. The dose received by the site of recurrence was investigated through registration of the posttreatment multiparametric prostate MRI with the HDR-BT treatment plan.nnnRESULTSnEight of 87 treated patients were found to have local recurrence after 19-Gy HDR-BT. Seven of the eight recurrences were at the site of initial bulk disease. Seven patients were found to have a more aggressive histology in the posttreatment biopsy. The mean volume of prostate that had received 100% of prescription dose was 97%. Mean dose to area of recurrence was 29.1xa0Gy, whereas dose to 98% and dose to 90% of the recurrence were 21.6xa0Gy and 23.2xa0Gy, respectively.nnnCONCLUSIONSnThe relapse pattern after a single 19-Gy HDR-BT is predominantly associated with the site of initial disease. This lends some rationale to future strategies of further focused dose escalation to initial site of disease, notwithstanding the fact that the calculated biologically equivalent dose using linear-quadratic assumptions is already very high.

Re-irradiation for painful bone metastases: evidence-based approach

The prognosis of patients with bone metastases has improved with the advent of increasingly effective systemic treatment and better supportive care. A growing number of bone metastases patients now outlive the duration of benefits from their initial treatment of radiotherapy (RT) while some patients fail to initially respond to RT. As such, re-irradiation (re-RT) may be required. The current review updates the literature on findings in the area of re-RT. In particular, the recent publication of the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) Symptom Control (SC20) trial shows that an 8 Gy treatment in a single fraction for re-RT is non-inferior and less toxic than 20 Gy in multiple fractions. Furthermore, patients responding to re-RT have experienced superior quality of life (QoL) and complain of less functional interference from pain; this provides a strong case in support of bone metastases patients being offered re-treatment. However, despite such findings, some specific patients will never respond to initial radiation or re-RT. New evidence suggests significant differences in bone markers between responders and non-responders, thus opening the possibility for further research into the use of such biomarkers for predicting prognosis and for the guidance of consequent treatment decisions.

Latest advances in the management of radiation-induced pain flare, nausea and vomiting

Palliative radiotherapy (RT) is an effective treatment for symptomatic bone metastases. However, pain flare, nausea and vomiting are common adverse effects associated with this treatment. The management of pain flare and radiation-induced nausea and vomiting (RINV) are important endpoints in palliative care. Our report documents the incidence, clinical importance, and advances in the management of these two adverse-effects. We recommend that antiemetic prophylaxis be given based on emetic risk category as outlined in the American Society of Clinical Oncology (ASCO) guidelines. Newer antiemetics investigated in the chemotherapy setting should also be studied in the radiation setting. As there are no guidelines for the use of pain flare prophylaxis at present, further research in this area is needed.

Funding source, conflict of interest and positive conclusions in neuro-oncology clinical trials

We aimed to test any association between authors’ conclusions and self-reported COI or funding sources in central nervous system (CNS) studies. A review was performed for CNS malignancy clinical trials published in the last 5xa0years. Two investigators independently classified study conclusions according to authors’ endorsement of the experimental therapy. Statistical models were used to test for associations between positive conclusions and trials characteristics. From February 2010 to February 2015, 1256 articles were retrieved; 319 were considered eligible trials. Positive conclusions were reported in 56.8% of trials with industry-only, 55.6% with academia-only, 44.1% with academia and industry, 77.8% with none, and 76.4% with not described funding source (pu2009=u20090.011). Positive conclusions were reported in 60.4% of trials with unrelated COI, 60% with related COI, and 60% with no COI reported (pu2009=u20090.997). Factors that were significantly associated with the presence of positive conclusion included trials design (phase 1) [OR 11.64 (95 CI 4.66–29.09), pu2009<u20090.001], geographic location (outside North America or Europe) [OR 1.96 (95 CI 1.05–3.79), Pu2009=u20090.025], primary outcomes (non-overall or progression free survival) [OR 3.74 (95 CI 2.27–6.18), pu2009<u20090.001], and failure to disclose funding source [OR 2.45 (95 CI 1.22–5.22), pu2009=u20090.011]. In a multivariable regression model, all these factors remained significantly associated with trial’s positive conclusion. Funding source and self-reported COI did not appear to influence the CNS trials conclusion. Funding source information and COI disclosure were under-reported in 14.1 and 17.2% of the CNS trials. Continued efforts are needed to increase rates of both COI and funding source reporting.

The role of adjuvant therapy in stage IA serous and clear cell uterine cancer: A multi-institutional pooled analysis

OBJECTIVEnAs the optimal adjuvant management of stage IA serous or clear cell endometrial cancer is controversial, a multi-institutional review was conducted with the objective of evaluating the appropriateness of various strategies including observation.nnnMETHODSnRetrospective chart reviews for 414 consecutive patients who underwent hysterectomy for FIGO stage IA endometrial cancer with serous, clear cell or mixed histology between 2004 and 2015 were conducted in 6 North American centers. Time-to-event outcomes were analyzed by Kaplan-Meier estimates, log-rank test, univariable and multivariable cox proportional hazard regression models.nnnRESULTSnPost-operative management included observation (50%), chemotherapy and radiotherapy (RT) (27%), RT only (16%) and chemotherapy only (7%). The 178 RT patients received external beam (EBRT, 16%), vaginal vault brachytherapy (VVB, 56%) or both (28%). Among patients without any adjuvant treatment, 5-year local control (LC), disease free survival (DFS) and cancer-specific survival (CSS) were 82% (95% confidence interval: 74-88), 70% (62-78) and 90% (82-94), respectively. CSS in patients without adjuvant treatment was improved with adequate surgical staging (100% vs. 87% (77-92), log-rank p=0.022). Adjuvant VVB was associated with improved LC (5-year 96% (91-99) vs. 84% (76-89), log-rank p=0.007) and DFS (5-year 79% (66-88) vs. 71% (63-77), log-rank p=0.033). Adjuvant chemotherapy was associated with better LC (5-year 96% (90-98) vs. 84% (77-89), log-rank p=0.014) and DFS (5-year 84% (74-91) vs. 69% (61-76), log-rank p=0.009). On multivariable analysis, adjuvant chemotherapy and VVB were associated with improved LC while adjuvant chemotherapy and age were significant for DFS.nnnCONCLUSIONSnIn stage IA serous or clear cell uterine cancer, adjuvant RT and chemotherapy were associated with better LC and DFS. Observation may be appropriate in patients who have had adequate surgical staging.

High dose-rate brachytherapy in the treatment of prostate cancer

High dose-rate (HDR) brachytherapy involves delivery of a high dose of radiation to the cancer with great sparing of surrounding organs at risk. Prostate cancer is thought to be particularly sensitive to radiation delivered at high dose-rate or at high dose per fraction. The rapid delivery and high conformality of dose results in lower toxicity than that seen with low dose-rate (LDR) implants. HDR combined with external beam radiotherapy results in higher cancer control rate than external beam only, and should be offered to eligible high and intermediate risk patients. While a variety of dose and fractionations have been used, a single 15 Gy HDR combined with 40–50 Gy external beam radiotherapy results in a disease-free survival of over 90% for intermediate risk and 80% for high risk. HDR monotherapy in two or more fractions (e.g., 27 Gy in 2 fractions or 34.5 Gy in 3) is emerging as a viable alternative to LDR brachytherapy for low and low-intermediate risk patients, and has less toxicity. The role of single fraction monotherapy to a dose of 19–20 Gy is evolving, with some conflicting data to date. HDR should also be considered as a salvage approach for recurrent disease following previous external beam radiotherapy. A particular advantage of HDR in this setting is the ease of delivering focal treatments, which combined with modern imaging allows focal dose escalation with minimal toxicity. Trans-rectal ultrasound (TRUS) based planning is replacing CT-based planning as the technique of choice as it minimizes or eliminates the need to move the patient between insertion, planning and treatment delivery, thus ensuring high accuracy and reproducibility of treatment.

The relationship of study and authorship characteristics on trial sponsorship and self-reported conflicts of interest among neuro-oncology clinical trials

ProposeTo examine the association between trial sponsorship sources, self-reported conflicts of interest (COI), and study and author characteristics in central nervous system (CNS) oncology clinical trials (CT).MethodsMEDLINE search was performed for original CT on “Central Nervous System Neoplasms“[Mesh]. The investigators assessed for relationships between funding source (industry, academic or cooperative, none, not described), COI (presented, none, or not reported), CT, and author characteristics.ResultsFrom 2010 to 2015, 319 CT were considered eligible. The majority of the studies involved primary gliomas (55.2%) and were Phase II CT (59.2%). Drug therapy was investigated in 83.0% of the CT. The remaining studies investigated surgery or radiotherapy. A minority of papers were published in journals with impact factor (IF) higher than >u200910 (16%) or in regions other than North America and Europe (20.4%). Overall, 83.1% of studies disclosed funding sources: 32.6% from industry alone, 33.9% from an academic or cooperative group, and 10.7% from a mixed funding model. COI data was reported by 85.9% of trials, of which 56.2% reported no COI and 43.8% reported a related COI. Significant predictors for sponsorship (industry and/or academia) on univariate analysis were study design, type of intervention, journal impact factor, study conclusion, transparency of COI and presence of COI. On multivariate analysis, type of intervention, (Pu2009<u20090.001), journal impact factor (IF) (Pu2009=u20090.003), presence of COI (Pu2009<u20090.001) and study conclusion (Pu2009=u20090.003) remained significant predictors of sponsorship. For predicting COI, significant variables on univariate analysis were disease type, type of intervention, journal IF, funding source, and intervention arm being related to sponsor. On multivariate analysis, disease type (Pu2009=u20090.003), journal IF (Pu2009<u20090.001), type of intervention (Pu2009=u20090.001), and funding source (Pu2009=u20090.008) remained significant.ConclusionsThe majority of CNS CT reported some external funding sources and non-related COI. We identified that drug trials, higher IF, presence of COI, and a neutral or negative study conclusion are associated with external funding. Likewise drug trials, higher IF, and glioma trials are associated with presence of COI.

Characterizing the impact of adaptive planning on image-guided perineal interstitial brachytherapy for gynecologic malignancies

PURPOSEnTo determine the dosimetric impact of organ and implant motion/deformation in the context of adaptive planning in image-guided gynecologic brachytherapy using a 3-fraction transperineal approach.nnnMETHODS AND MATERIALSnTwenty-six patients were analyzed. Each patient was treated with three fractions given over a 24-h period using a single insertion. A planning CT scan (±MRI) was acquired before the first fraction. A verification scan was taken within 1 h following the second fraction. A single plan was delivered for Fractions 1 and 2 with an adaptive plan delivered for Fraction 3. Two evaluation frameworks were established. Framework 1 investigated the effects of motion/deformation from both implant and organs. Framework 2 investigated the impact of implant motion/deformation alone. Differences in high-risk clinical target volume (HRCTV) D90%, V100%, and bladder/rectum D2cc were assessed.nnnRESULTSnFrom implant to verification, the HRCTV D90% and V100% decreased significantly (5.0%, p < 0.01; 3.1%, p < 0.01) and rectal D2cc was significantly higher (12.2%, pxa0= 0.02). Adaptive planning recouped these changes. Implant changes resulted in a reduction in HRCTV dose and coverage, but no significant effect was seen in the bladder or rectum.nnnCONCLUSIONSnAdaptive planning represents an important aspect of perineal-based interstitial image-guided brachytherapy given in three fractions; its absence would result in plan degradation.

Quality of life in responders after palliative radiation therapy for painful bone metastases using EORTC QLQ-C30 and EORTC QLQ-BM22: results of a Brazilian cohort

BACKGROUNDnBone metastases cause pain, suffering and impaired quality of life (QoL). Palliative radiotherapy (RT) and/or chemotherapy are effective methods in controlling pain, reducing analgesics use and improving QoL. This study goal was to investigate the changes in QoL scores among patients who responded to palliative treatment.nnnMETHODSnA prospective study evaluating the role of radiation therapy in a public academic hospital in São Paulo-Brazil recorded patients opioid use, pain score, Portuguese version of QLQ-BM22 and QLQ-C30 before and 2 months after radiotherapy. Analgesic use and pain score were used to calculate international pain response category. Overall response was defined as the sum of complete response (CR) and partial response (PR). CR was defined as pain score of 0 with no increase in analgesic intake whereas PR was defined as pain reduction ≥2 without analgesic increase or analgesic reduction in ≥25% without increase in pain at the treated site.nnnRESULTSnFrom September 2014 to October 2015, 25 patients with bone metastases responded to RT or chemotherapy (1 CR, 24 PR). There were 8 male and 17 female patients. The median age of the 25 patients was 59 (range, 22 to 80) years old. Patients primary cancer site was breast [11], prostate [5], lung [2], others [7]. For QLQ-BM 22, the mean scores of 4 categories at baseline were: pain site (PS) 39, pain characteristics (PC) 61, function interference (FI) 49 and psycho-social aspects (PA) 57. At 2 month follow up, the scores were PS 27, PC 37, FI 70 and PA 59. Statistical significant improvement (P<0.05) was seen in PS, PC, FI but not PA. In the QLQ-C30, the scores were not statistically different for all categories, except for pain that demonstrated a 33 point decrease in the median pain score domain (66 to 33).nnnCONCLUSIONSnResponders to RT at 2 months presented improvement in BM22 and C30 pain domains, and also improvement in functional interference domain of the BM22 questionnaire.