First Day Of Radiotherapy Research Articles

Study of Indicators for Early and Rapid Diagnosis of Radiation Injury Is the Most Important in Patients With Cancer During Radiotherapy.

Objective:To establish a complete technical solution for the radiation biological dose estimation, to enable prediction of individuals’ response to radiotherapy (RT), and to control treatment dose for reduced irradiation injury and promote repair; and to evaluate the risk of radiation-induced late effects for patients undergoing external photon beam RT and provide the reliable dose–response relationships.Methods:Select 49 tumor patients using 60Co and linear accelerator for radiation therapy; initial radiation dose was 250 cGy. Chromosome aberration and blood count were analyzed before radiation therapy and 2 hours after the first day of RT.Results:Two hours after the first day of RT, peripheral blood cell count of lymphocytes of patients with cancer was significantly decreased (P < .01). The frequency of chromosome aberration was higher (P < .01).Conclusion:High-dose radiation of the radiation therapy makes significant injuries to peripheral blood lymphocytes.

Transplanted Antler Stem Cells Stimulated Regenerative Healing of Radiation-induced Cutaneous Wounds in Rats

Radiation-induced cutaneous injury is the main side effect of radiotherapy. The injury is difficult to cure and the pathogenesis is complex. Mesenchymal stem cells (MSCs) serve as a promising candidate for cell-based therapy for the treatment of cutaneous wounds. The aim of the present study was to investigate whether antler stem cells (AnSCs) have better therapeutic effects on radiation-induced cutaneous injury than currently available ones. In this study, a rat model of cutaneous wound injury from Sr-90 radiation was used. AnSCs (1 × 106/500 μl) were injected through the tail vein on the first day of irradiation. Our results showed that compared to the control group, AnSC-treated rats exhibited a delayed onset (14 days versus 7 days), shorter recovery time (51 days versus 84 days), faster healing rate (100% versus 70% on day 71), and higher healing quality with more cutaneous appendages regenerated (21:10:7/per given area compared to those of rat and human MSCs, respectively). More importantly, AnSCs promoted much higher quality of healing compared to other types of stem cells, with negligible scar formation. AnSC lineage tracing results showed that the injected-dye-stained AnSCs were substantially engrafted in the wound healing tissue, indicating that the therapeutic effects of AnSCs on wound healing at least partially through direct participation in the wound healing. Expression profiling of the wound-healing-related genes in the healing tissue of AnSC group more resembled a fetal wound healing. Revealing the mechanism underlying this higher quality of wound healing by using AnSC treatment would help to devise more effective cell-based therapeutics for radiation-induced wound healing in clinics.

Utility of topical agents for radiation dermatitis and pain: a randomized clinical trial.

Although topical agents are often provided during radiation therapy, there is limited consensus and evidence for their use prophylactically to prevent or reduce radiation dermatitis. This was a multi-site, randomized, placebo-controlled, blinded study of 191 breast cancer patients to compare the prophylactic effectiveness of three topical agents (Curcumin, HPR Plus™, and Placebo) for reducing radiation dermatitis and associated pain. Patients applied the topical agent to their skin in the radiation area site three times daily starting the first day of radiation therapy (RT) until 1 week after RT completion. Of the 191 randomized patients, 171 patients were included in the final analyses (87.5% white females, mean age = 58 (range = 36-88)). Mean radiation dermatitis severity (RDS) scores did not significantly differ between study arms (Curcumin = 2.68 [2.49, 2.86]; HPR Plus™ = 2.64 [2.45, 2.82]; Placebo = 2.63 [2.44, 2.83]; p = 0.929). Logistic regression analyses showed that increased breast field separation positively correlated with increased radiation dermatitis severity (p = 0.018). In patients with high breast field separation (≥ 25 cm), RDS scores (Curcumin = 2.70 [2.21, 3.19]; HPR Plus™ = 3.57 [3.16, 4.00]; Placebo = 2.95 [2.60, 3.30]; p = 0.024) and pain scores (Curcumin = 0.52 [- 0.28, 1.33]; HPR Plus™ = 0.55 [- 0.19, 1.30]; Placebo = 1.73 [0.97, 2.50]; p = 0.046) significantly differed at the end of RT. Although there were no significant effects of the treatment groups on the overall population, our exploratory subgroup analysis suggests that prophylactic treatment with topical curcumin may be effective for minimizing skin reactions and pain for patients with high breast separation (≥ 25 cm) who may have the worst skin reactions.

Solitary Plasmacytoma Treated by Lenalidomide-Dexamethasone in Combination with Radiation Therapy: Clinical Outcomes

PurposeThe study evaluates the results of the concurrent use of lenalidomide-dexamethasone with intensity modulated radiation therapy (IMRT) for solitary plasmacytoma in terms of toxicity and outcome. Methods and MaterialsForty-six patients were treated for histologically proven solitary plasmacytoma (SP) between June 2007 and June 2018 in our Department (Curie Institute, Paris, France). All patients received IMRT. The median total dose was 40 Gy (range, 40-46). Prescription of concurrent lenalidomide-dexamethasone with radiation therapy was left to the discretion of the referring hematologist-oncologist and started the first day of radiation therapy for 4 cycles. ResultsTwenty-seven solitary plasmacytoma were treated with IMRT alone and 19 with lenalidomide-dexamethasone in association with IMRT. At 5 years, the local control, multiple myeloma–free survival (MMFS), and progression-free survival (PFS) rates were 96.3%, 85.4%, and 60%. MMFS and PFS were significantly higher in the IMRT plus lenalidomide-dexamethasone group compared with IMRT alone group (100% vs 77.1%, P = .02 and 81.7% vs 48.4%, P = .047, respectively). No major toxicity was found in either group. ConclusionsLenalidomide-dexamethasone in association with IMRT in the treatment of solitary plasmacytoma is safe and improves MMFS and PFS. Further prospective and comparative studies are needed to confirm these results.

Lymphocyte-sparing effect of stereotactic body radiation therapy compared to conventional fractionated radiation therapy in patients with locally advanced pancreatic cancer

BackgroundConventionally fractionated (CF) radiation therapy (RT) has been associated with lymphopenia, leading to compromised overall survival (OS) in cancer patients. It currently remains unknown if stereotactic body (SB) RT induces lymphopenia to the same degree. The aim of this study is to determine if SBRT with either chemotherapy (CMT) (Fluorouracil (5FU) or capecitabine) or Nelfinavir (NFV) to pancreatic adenocarcinoma induces lymphopenia to the same degree as CFRT with 5FU or capecitabine and how any associated difference affects patient survival outcomes.MethodsMedical records of pancreatic adenocarcinoma patients treated with induction CMT followed by RT with concurrent CMT or NFV were reviewed. Patients with total lymphocyte counts (TLCs) available both prior to and following initiation of RT were included. Three groups were identified: CFRT/CMT, SBRT/CMT, and SBRT/NFV. Median delivered RT doses for CFRT and SBRT were 50.4 Gy in 1.8 Gy fractions and 35 Gy in 7 Gy fractions, respectively. TLCs from day 0 (the first day of RT) to 40 were recorded and analyzed using the Kruskal-Wallis test with p-values adjusted with Bonferroni’s method. Linear regressions were utilized to estimate the slope of TLCs as it changes with time and survival analysis was performed via Kaplan-Meier plots.ResultsOne hundred patients were identified (28 CFRT/CMT, 27 SBRT/CMT, 45 SBRT/NFV). Median pre-RT TLCs were not different among groups. Median lowest TLCs were significantly lower (p < 0.0001) and median TLCs reduction over time were significantly greater (p < 0.0001) in the CFRT group than SBRT groups. There was no difference in lowest TLCs or TLCs reduction over time between SBRT groups. Across all groups, the median time to lowest TLCs was similar. Survival analysis revealed no significant difference in median OS between SBRT and CFRT groups. However, in patients with surgery, Median OS for patients with SBRT/CMT was significantly higher than in those with SBRT/NFV (p = 0.03).ConclusionsCompared to CFRT, SBRT is associated with less lymphopenia. Further study of the effect of radiation technique on immune status is warranted.

The Phase 1/2 ACCEPT Trial: Concurrent Cetuximab and Intensity Modulated Radiation Therapy with Carbon Ion Boost for Adenoid Cystic Carcinoma of the Head and Neck

The adenoid cystic carcinoma (ACC), Erbitux, and Particle Therapy (ACCEPT) phase 1/2 trial (NCT01192087) evaluated a combined-modality approach (concurrent cetuximab and intensity modulated radiation therapy with carbon ion boost) for newly diagnosed nonmetastatic head and neck ACC. Twenty-three patients with ACC were enrolled between June 2012 and June 2017 after initial diagnosis or postoperatively. All received a 400 mg/m2 cetuximab loading dose a week before radiation therapy, followed by weekly 250 mg/m2 doses starting on the first day of radiation therapy. The carbon ion radiation therapy boost was 24 Gy (relative biological effectiveness) in 8 daily fractions, followed by intensity modulated radiation therapy (54 Gy). The primary endpoint was safety and feasibility (defined based on Common Terminology Criteria for Adverse Events grade ≥3 events). Secondary endpoints included local and distant relapse, disease-free survival, and overall survival. Disease was most commonly in the paranasal sinuses (30%), palate (17%), and nasopharynx (17%). Nine (39%) patients underwent surgery (R1: 22%, R2: 78%). Median follow-up was 38.5 months. No patients experienced grade 4 to 5 events. Rates of grade 3 rash and radiation dermatitis were 17% and 22%, respectively. Grade 2 and 3 mucositis and dysgeusia occurred in 43% and 48% and in 9% and 0%, respectively. Grade 2 to 3 dysphagia and xerostomia were present in 43% and 4% and in 26% and 0%, respectively. At last follow-up, 5 (22%) patients experienced in-field relapse and 6 (26%) developed distant metastases. The 3-year disease-free survival was 67%, and median overall survival was 54 months. Outcomes of this trial were satisfactory. Although the trial did not meet the predefined criteria of feasibility owing to the comparatively high rates of grade 3 dermatitis, numbers are comparable to existing data on cetuximab + radiation therapy.

1172TiP - Concurrent chemotherapy and external radiation therapy: An open label non-inferiority phase III randomized controlled trial of weekly versus three weekly cisplatin and radical radiotherapy in locally advanced head and neck squamous cell carcinoma: CONCERT trial

BackgroundLA-HNSCC is treated with concurrent chemo-radiation. Majority of guidelines recommend bolus Cisplatin in the dose of 100mg/m2 (on days 1, 22, and 43). The meta-analysis reported by MACH-NC group found a greater benefit for platinum-based chemotherapy as compared with other protocols. Multiple studies back this notion. Other options are weekly cisplatin (30-40mg/m2) or split course radiation and combination of DDP+5FU. Alternative dosing schedules (e.g., 30 to 40mg/m2 weekly, 6mg/m2 daily, or 20mg/m2 daily for five days weeks 1 and 5) are used because of improved patient tolerance and ease of administration. 30mg/m2 of weekly cisplatin has found to be inferior to 3 weekly 100mg/m2. Three weekly schedules is the benchmark for further trials. In practice many of physicians alternatively, use low dose. 40mg/m2 has been found superior to RT alone in a phase II randomized study. Whether 40mg/m2 weekly cisplatin is inferior to 100mg/m2 is not known. Based on our previous report and our long experience we are quite comfortable with weekly Cisplatin (in the dose of 40mg/m2), and hypothesize that weekly Cisplatin (40mg/m2) times 6-7 is non-inferior to 3 weekly Cisplatin 100mg/m2 times three (days 1,22,43). Trial designMulticentric Open labelled, non-inferiority randomized controlled phase III trial. Sample size was calculated expecting 60% LRC (loco-regional control) rate at 2 years in control arm, and 65% in experimental arm, with 80%power of study, alpha error 5%, non-inferiority margin of 10%. Based on these parameters each arm will require143 patients (including 10% lost to follow up/protocol violations etc.). Main Inclusion criteria: Newly diagnosed, chemo/radiotherapy naïve, biopsy or cytology proven, locally advanced head and neck squamous cell carcinoma excluding nasopharyngeal carcinoma (stage III and IV without distant metastases). ARM A: Three weekly Cisplatin100mg/m2 (Day1, 22, 43) to be started on first day of radiation and given on days 1,22,43 ARM B: Weekly Cisplatin40mg/m2 times 6-7 Primary objective: Loco Regional Control Rate at 2 years. Clinical trial identificationCTRI/2018/03/012422 release date 08/03/2018. Legal entity responsible for the studyAtul Sharma. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Pain Flare-Effect Prophylaxis With Corticosteroids on Bone Radiotherapy Treatment: A Systematic Review.

Radiotherapy for metastatic bone pain can induce a transitory increase in pain known as pain flare. Several studies have described the use of prophylactic corticosteroids to prevent pain flare. However, the role and efficacy of corticosteroids to prevent pain flare remain unclear. To summarize the available evidence with regard to the efficacy and toxicity of prophylactic corticosteroids for the prevention of pain flare. This was a systematic review (PROSPERO protocol CRD42018090351) of peer-reviewed studies published in the Cochrane, Medline, and Scopus databases through September 2018. Studies carried out in adult patients treated with radiotherapy for bone metastases who received prophylactic corticosteroids to prevent pain flare were eligible for inclusion. The Cochrane Collaboration tool was used to assess risk of bias. The evidence grade was determined according to the GRADEpro tool. A total of 4,407 studies were identified. Of these, 4 clinical trials (CT) and 1 prospective cohort study met the inclusion criteria. The overall incidence of pain flare was 28%, and 21% vs. 37% in the prophylaxis vs. non-prophylaxis groups; the relative risk reduction was 43%. In the 3 studies that compared corticosteroids to placebo, the relative risk reductions were 25%, 67%, and 72%. The most common treatment regimen was oral dexamethasone at 8 mg once daily from the first day of radiotherapy for 5days. One study administered methylprednisolone. No severe toxicity was reported in any of the studies. Overall, the findings of this systematic review indicate that glucocorticoids appear to be an effective prophylactic treatment to prevent pain flare in patients undergoing radiotherapy for bone metastases. New CT are needed to confirm these results and to determine the optimal dose of dexamethasone.

Interim PSA: Predicting for Biochemical Failure during Salvage Radiotherapy Following Prostatectomy

It is challenging to identify patients at higher risk of biochemical failure following salvage radiotherapy after having a radical prostatectomy. This work aims to determine if an interim PSA during radiotherapy would predict two year biochemical failure for patients who have salvage radiotherapy for a rising PSA following a radical prostatectomy for prostate cancer. A total of 185 patients in one center having salvage radiotherapy following a radical prostatectomy to a dose of 68Gy without androgen deprivation therapy between the years of 2010 and 2016 had their PSA recorded on the first day of radiotherapy, and again after completing the 25th fraction of 34 total fractions. Biochemical failure after radiotherapy was defined as a PSA value ≥0.2ng/mL within two years following radiotherapy. Univariate and multivariate Cox regression models were used for statistical analysis using statistical software. Factors investigated in univariate analysis other than a drop in PSA during radiotherapy included age, a Gleason score above 7, surgical margins status, the presence of extracapsular extension, PSA doubling time prior to radiotherapy, PSA at the time of radiotherapy, the presence of a detectable post-operative PSA immediately after surgery, whether or not a pelvic lymph node dissection was performed and whether or not there was seminal vesicle invasion. Factors with a p value <0.2 in univariate analysis were then used in a multivariate analysis. The two year freedom from biochemical failure was 60% (95% CI: 53% to 67%). Table 1 shows that on multivariate analysis, a drop in PSA during radiotherapy (p=0.003) and a positive surgical margin (p<0.0001) were significant factors for freedom from subsequent biochemical failure, while seminal vesicle invasion was associated with biochemical failure at two years (p=0.007). A PSA rise during salvage radiotherapy is predictive of biochemical failure at two years (HR 2.05). Factors such as seminal vesicle invasion and a negative surgical margin also predict for poor responders to salvage radiotherapy. If this is confirmed in further studies, then it may allow salvage radiotherapy to be abandoned at 50Gy into the treatment course, thereby potentially averting further futile radiotherapy and the risks of higher dose salvage treatment.Abstract 2619; Table 1Prognostic factors for biochemical failure at two years on multivariate analysis. *[Reference value]PSA During RadiotherapySurgical MarginsSeminal Vesicle InvasionGleason scoreSame or riseFallNegativePositiveYesNo>7≤7HR(95% Cl)2.050 (1.273-3.299)1*2.437 (1.493-3.978)1*2.044 (1.218-3.431)1*1.247 (0.731-2.127)1*P Value0.003<0.0010.0070.418 Open table in a new tab

First day of radiotherapy for women with breast cancer: predictors of anxiety.

Radiotherapy treatment may generate anxiety, especially on the first day of treatment. This study aimed to identify potential predictors of radiotherapy-related anxiety in women with breast cancer before treatment initiation, interms of treatment concerns and trait anxiety. This transversal study included 94 patients from one Radiation Oncology Department, who had beendiagnosed with primary breast cancerand who had been prescribed external radiotherapy for the first time. Patients completed a Treatment Concerns Questionnaire and the State-Trait Anxiety Inventory (STAI) before the first treatment session. Women identified radiation involved in the procedure and treatment efficacy as major concerns surrounding radiotherapy. No significant differences were found between patients with higher and lower state anxiety scores, or by age, level of education, cancer treatment protocolused, prior information given about treatment, or report of doubts before treatment initiation. In the final model, the combination of trait anxiety (49.1% of the total variance) with two treatment-related concerns, regarding radiation andthe duration of treatment (plus 10.8% of the total variance), significantly predicted treatment-related anxietyexperienced on the first day of treatment. Our findings highlight the need to identify women with moderate or higher levels of trait anxiety before radiotherapy initiation and to provide them with a more approach to personalized care, adjusted to their specific concerns and susceptibility to anxious reactions. Effective education sessions involving the discussion of specific treatment concerns, and anxiety coping strategies training should be developed and applied in initial interactions with breast cancer patients.

Long-term treatment outcomes in patients with low rectal cancer

Objective: to assess the effect of preoperative treatment option on the number of sphincter-preserving operations (SPO) in patients with low rectal cancer. Materials and methods . The patients with low rectal cancer (0—6 cm from anocutaneous line) were randomized into 3 groups: in the 1st control group surgery was performed in 0—3 days after completion of short-course radiotherapy (5 х 5 Gy). Patients in the 2nd control group received identical radiotherapy but the interval before surgery was extended to 42 ± 3 days. Patients in the study group received treatment identical to 2nd control group with 2 additional courses of monochemotherapy with capecitabine, starting on the first day of radiotherapy. The primary endpoint was the number of SPO. Complete pathomorphologic response rate, overall survival, tumor-specific survival and event-free 5-year survival were also assessed as secondary endpoints. Results. Data on 129 patients was analyzed: 46 in the 1st control group, 43 in the 2nd control group, 40 in the study group. The proportion of SPO was 41,3 ± 7,3 % in the 1st group, 69,7 ± 7,0 % and 77,5 ± 6,6 % in the 2nd group and study group, respectively. Complete histological response was achieved in 15 % of patients in study group, comparing to 14,3 % of patients in the 2nd group. Overall 5-year survival in this study was estimated to be 77,8 ± 4,5%, tumor-specific survival — 89,7 ± 3,7 %, event-free survival — 90,1 ± 2,9 %, with no significant differences between groups. Conclusion. Short-course radiotherapy (5 х 5 Gy) with 6-week interval before surgery resulted in increase of SPO rate with no affect on oncologic outcome.

IDO1 Inhibition Overcomes Radiation-Induced “Rebound Immune Suppression” by Reducing Numbers of IDO1-Expressing Myeloid-Derived Suppressor Cells in the Tumor Microenvironment

The limitation of hypofractionated radiation efficacy is due partly to the immunosuppressive tumor microenvironment. Indoleamine 2,3-dioxygenase 1 (IDO1) is an important regulator of tumor immune suppression. We evaluated the effects of IDO1 in hypofractionated radiation using a Lewis lung carcinoma (LLC) mouse model and tested whether IDO1 inhibition could sensitize those tumors to hypofractionated radiation. Bilateral LLC tumors were established in C57BL/6 mice. Primary tumors were treated with 3 fractions of either 12Gy or 6Gy, and the IDO1 inhibitor INCB023843 was given starting on the first day of radiation. Plasma tryptophan and kynurenine levels were quantified by liquid chromatography and tandem mass spectrometry. Tumor-infiltrating immune cells were isolated from the tumors, stained, and quantified by flow cytometry. The combination of INCB023843 and three 12-Gy fractions led to better tumor control and survival than radiation alone; INCB023843 plus three 6-Gy fractions had no benefit. IDO1 expression by tumor-infiltrating immune cells was increased by three 12-Gy doses and inhibited by the addition of INCB023843. Nearly all IDO1+ immune cells were also F4/80+. Percentages of IDO1+F4/80+ immune cells were drastically increased by three 12-Gy fractions and by three 6-Gy fractions, but only INCB023843 combined with three 12-Gy fractions reduced those percentages. IDO1+F4/80+ immune cells were further found to be CD11b+, Gr1-intermediate-expressing, CD206-, and CD11c- (ie, myeloid-derived suppressor cells). Three 12-Gy fractions also increased the percentages of tumor-infiltrating T regulatory cells and CD8+ T cells, but adding INCB023843 did not affect those percentages. In addition to its immune activation effects, hypofractionated radiation induced "rebound immune suppression" in the tumor microenvironment by activating and recruiting IDO1-expressing myeloid-derived suppressor cells in a dose-dependent manner. Adding an IDO1 inhibitor to hypofractionated radiation reduced the percentages of these cells, overcame the immune suppression, and sensitized LLC tumors to hypofractionated radiation.

The impact of the time to start radiation therapy on overall survival in newly diagnosed glioblastoma.

The standard treatment for newly diagnosed glioblastoma includes maximal safe surgical resection followed by concurrent radiation therapy and temozolomide (TMZ) and maintenance TMZ. The impact of time to start radiation therapy (TRT) on overall survival (OS) in glioblastoma patients is controversial. The study aimed to evaluate the impact of TRT on OS in patients diagnosed with glioblastoma who received standard treatment. In this retrospective study, we included patients with confirmed diagnosis of glioblastoma treated from 2011 to 2016. TRT was defined as the time between surgery (biopsy or resection) and the first day of radiation therapy. The endpoint was OS. The patients were divided according to the TRT in three categories: < 30days, 30-60days and ≥ 60days. A total of 134 patients were included with a mean age of 51.82years (range 19-78years). Median TRT was 80days. On univariate and multivariable analysis, we identified age as the only significant independent predictor for OS. There was no statistically significant negative impact of TRT on OS (p = 0.47). There was no clear evidence that delaying post-operative combined chemoradiotherapy negatively impacts OS, not even for TRT longer than 60days.

Topical silymarin administration for prevention of acute radiodermatitis in breast cancer patients: A randomized, double-blind, placebo-controlled clinical trial.

Radiation-induced dermatitis is one of the most common side effects of radiotherapy. Silymarin, a flavonoid extracted from the Silybum marianum, exhibits antioxidant and anti-inflammatory activities. The purpose of this study was to investigate the efficacy of silymarin gel in prevention of radiodermatitis in patients with breast cancer. During this randomized, double-blinded, placebo-controlled clinical trial, the preventive effect of silymarin 1% gel was assessed in comparison with placebo, on radiodermatitis occurrence. Forty patients randomly received silymarin gel or placebo formulation on chest wall skin following modified radical mastectomy, once daily starting at the first day of radiotherapy for 5weeks. Radiodermatitis severity was assessed weekly based on Radiation Therapy Oncology Group (RTOG) and National Cancer Institute Common Terminology for Adverse Events (NCI-CTCAE) criteria radiodermatits grading scale for 5weeks. The median NCI-CTCAE and RTOG scores were significantly lower in silymarin group at the end of the third to fifth weeks (p value<0.05). The scores increased significantly in both placebo and silymarin groups during radiotherapy, but there was a delay in radiodermatitis development and progression in silymarin group. Prophylactic administration of silymarin gel could significantly reduce the severity of radiodermatitis and delay its occurrence after 5weeks of application.

Biophysical skin measurements to evaluate the effectiveness of photobiomodulation therapy in the prevention of acute radiation dermatitis in breast cancer patients.

The purpose of this study was to evaluate objectively the effectiveness of photobiomodulation therapy (PBMT) for the prevention of acute radiation dermatitis (ARD) by using biophysical skin measurements. A randomized, placebo-controlled trial with 120 breast cancer patients who underwent an identical radiotherapy (RT) regimen post-lumpectomy was performed (TRANSDERMIS trial). Patients were randomized to receive PBM (808nm CW/905nm pulsed, 168mW/cm2, spot size 19.6cm2, fluence 4J/cm2) or placebo treatments from the first day of RT (2×/week). Biophysical skin measurements were collected to assess the skin pigmentation and barrier function. Measurements were collected at the first day of RT, a RT dose of 40Gray (Gy), and the end of RT (66Gy). The incidence of moist desquamation was significantly higher in the control than in the PBMT group at the end of RT (30 vs. 7%, respectively, odds ratio = 6, p = 0.004). The biophysical skin measures showed that the mean percentage change from the baseline transepidermal water loss (TEWL), erythema, and melanin values was significantly higher in the control than in the PBMT group at the end of RT (ps < 0.05). Logistic regression analysis revealed that the risk on moist desquamation was significantly increased for patients with a large (> 800cc) breast volume (odds ratio = 4, p = 0.017). This is the first randomized controlled trial demonstrating by objective measurements that PBMT is effective in reducing the incidence of moist desquamation in breast cancer patients undergoing RT. Additionally, a large breast volume is an important risk factor for the development of moist desquamation.

CIED malfunction in patients receiving radiation is a rare event that could be detected by remote monitoring.

An increasing number of patients with cardiac devices require radiation therapy for treatment of a variety of cancers. This study aimed to identify the incidence and predictors of cardiac implantable electronic devices (CIED) malfunction in a real-world population that has received radiation therapy. This retrospective cohort study included 109 adult patients who received radiation therapy at the University of Rochester Medical Center, Radiation Oncology Department, between 2000 and 2015. Sixty patients had pacemakers and 49 had automatic implantable cardioverter defibrillators. Subjects received either high energy (16 MV) and/or low energy (6 MV) photon beams with or without electron beams (6-16 MeV). We included interrogations done from first day of radiation and up to 3 months' postradiation therapy. Outcomes analyzed were device-related malfunctions and device-related clinical events. Fisher's exact, Wilcoxon, and Kruskall-Wallis tests were used for bivariate analysis. Logistic regression with robust adjustment was used for multivariate analysis. We identified six device-related malfunctions. All events were minor and included partial settings reset leading to loss of historical data, pacing thresholds changes, lead impedance changes, and LV output increase. Two patients had device-related clinical events, including dyspnea and diaphragmatic-stimulation. In bivariate analysis, CIED malfunction was associated with CIED duration in situ. In multivariate analysis, there was no significant statistical association between adverse events and beam energy type, CIED location, or dose of radiation delivered to the target. CIED malfunctions are uncommon in real-world patients and associated with minor clinical events. In our cohort, remote CIED monitoring would have identified all events.

Combined abiraterone acetate plus prednisone, salvage prostate bed radiotherapy and LH-RH agonists (CARLHA-GEP12) in biochemically-relapsing prostate cancer patients following prostatectomy: A phase I study of the GETUG/GEP.

BackgroundTo establish the maximum tolerated dose of abiraterone acetate plus prednisone (AA) combined with salvage radiotherapy (SRT) and goserelin in a phase 1 study in men with rising PSA following radical prostatectomy.MethodsAA was given during one month before SRT at 1000 mg PO once daily, then 750 mg (Dose Level 1, DL1) or 1000 mg (DL2) during 5 months combined with 6-months goserelin by injection on the first day of irradiation (scheme NEO) or one month before starting SRT (scheme CONCO).ResultsIn scheme NEO at DL1, 2/9 patients did not achieve castration levels of testosterone. 4/9 patients (44%) presented with grade 3 liver enzyme elevation. In scheme CONCO testosterone dropped to undetectable levels. At DL1, 6 patients were recruited, with no dose limiting toxicities. At DL2, 2/3 patients presented with grade 3 liver enzyme elevation occurring during SRT.ConclusionsWhen AA was administered without goserilin, only 78% achieved castration levels. AA combined with SRT and goserilin did not increase pelvic toxicity, but lead to an unsuspected high frequency of grade 3 liver toxicity. The phase II recommended dose of AA combined to goserelin and SRT is 750 mg.

Survival Impact of Treatment Interval Delays in Head and Neck Cancer

Multidisciplinary head and neck cancer management must reconcile increasingly sophisticated subspecialty care with timeliness of care. Prior studies have examined the individual effects of prolonging diagnosis to treatment interval (DTI), postoperative interval, and radiation interval but not considered them collectively. We investigate the shared impact of these interwoven intervals on head and neck cancer patients completing definitive surgery with postoperative radiation. Head and neck cancer patients undergoing upfront surgical resection with adjuvant radiation were identified in the National Cancer Database between 2004 and 2013. Patients treated with curative intent who completed full-course radiation therapy were included. Diagnosis to treatment interval was defined as the time from diagnosis until surgery. Postoperative interval was defined as the time from surgery to the first day of radiation. Radiation interval was defined as the time from the first to the last day of radiation. Multivariable models were constructed to assess the association between treatment delays and overall survival. Overall, 15,177 patients were evaluated. Prolonged DTI, postoperative interval, and radiation interval all were associated with impaired survival in univariate analysis. After adjustment for covariates, only prolonged postoperative interval (P = .006) and radiation interval (P < .001) independently predicted for risk of death, while the association of DTI with overall survival disappeared. Using multivariable restricted cubic spline functions, mortality risk escalated continuously for postoperative interval with each additional day, plateauing at 74 days (cumulative HR 1.25, 95% CI 1.11-1.32, P < .001). Similarly, mortality risk increased continuously for radiation interval with each additional day, peaking at 56 days (cumulative HR 1.31, 95% CI 1.22-1.39, P < .001). Delays beyond these change points were not associated with additional survival decrements. Delays in postoperative interval and radiation interval are independently associated with mortality risk. The hazard conferred suggest that attention to these physician-modifiable covariates could considerably improve prognosis. Delays in initiating treatment conversely do not appear to impact survival when appraised in conjunction with the entire treatment course.

Efficacy of intensive radiotherapy combined with mesylate apatinib for treatment of elderly patients with locally advanced cardia cancer and its effect on vascular endothelial growth factor receptor

Objective To observe the clinical effect of intensity modulated radiation therapy (IMRT) combined with apapatinib mesylate in the treatment of elderly patients with locally advanced cardia adenocarcinoma and its effect on vascular endothelial growth factor receptor (VEGFR). Methods Forty-six elderly patients with locally advanced cardia cancer who were unwilling to accept surgery or couldn't get complete removal of cancers in Xuzhou Hospital Affiliated to Jiangsu University between January 2015 and April 2016 were collected. All the patients were randomly divided into the control group (23 cases) and the observation group (23 cases) according to the random number table method. The control group received radiotherapy alone. In the observation group, oral apatinib (500 mg/d) was taken in the first day of radiotherapy after breakfast until the disease progress or death occurred. Results The total effective rate was 92% (19/23) in the observation group and 60% (10/23) in the control group. There was a significant difference between the two groups (χ2= 5.86, P 0.05). Hypertension, proteinuria and rash response in the observation group were increased compared with the control group, but no Ⅳ grade of adverse reactions occurred. The median progression-free survival time was 10 months in the observation group and 8 months in the control group respectively (P= 0.01). Conclusion IMRT combined with apatinib in the treatment of elderly patients with locally advanced gastric cardia has a favorable efficacy and tolerance. Key words: Cardia neoplasms; Radiotherapy, intensity-modulated; Vascular endothelial growth factors

Prevention of acute radiodermatitis by photobiomodulation: A randomized, placebo-controlled trial in breast cancer patients (TRANSDERMIS trial).

Acute radiodermatitis (RD) is a distressing and painful skin reaction that occurs in 95% of the patients undergoing radiotherapy (RT). The aim of this study was to evaluate the effectiveness of photobiomodulation therapy (PBMT) in the prevention of acute RD in breast cancer (BC) patients undergoing RT. This study was a randomized, placebo-controlled trial including 120 BC patients that underwent an identical RT regimen post-lumpectomy. Patients were randomly assigned to the laser therapy (LT) or placebo group, with 60 patients in each group. Laser or placebo treatments were applied 2 days a week, immediately after the RT session, starting at the first day of RT. PBMT was delivered using a class IV MLS® M6 laser that combines two synchronized laser diodes in the infrared range (808-905 nm) with a fixed energy density (4 J/cm2 ). Skin reactions were scored based on the criteria of the Radiation Therapy Oncology Group (RTOG) and the Radiation-Induced Skin Reaction Assessment Scale (RISRAS). The patients completed the Skindex-16 questionnaire to evaluate their quality of life. All the measurements were collected at the first day, at a RT dose of 40 Gray (Gy), and at the end of RT (total dose 66 Gy). At a RT dose of 40 Gy, there was no significant difference between the groups in the distribution of RTOG grades. However, at the end of RT the severity of the skin reactions significantly differed between the two groups (P = 0.004), with a larger percentage of patients experiencing RTOG grade 2 or higher (e.g., moist desquamation) in the placebo group (30% vs. 6.7%, for the placebo and laser group, resp.). The objective RISRAS score confirmed these results. In addition, the Skindex-16 and RISRAS subjective score demonstrated that the patients' quality of life was significantly better in the LT than in the control group. The results of this trial show that PBMT is an effective tool to prevent the development of grade 2 acute RD or higher in BC patients. In addition, it also reduces the patients' symptoms related to RD. Lasers Surg. Med. © 2018 Wiley Periodicals, Inc.