Esophageal Toxicity Research Articles

CLINICAL OUTCOME USING WEEKLY PACLITAXEL WITH RADIATION IN LOCALLY ADVANCED LUNG CANCER

Background: Non-small cell lung cancer is the second most common malignancy worldwide with very high mortality rate. The aim of this study is to evaluate the locoregional response and toxicity prole using weekly paclitaxel along with radiation in locally advanced inoperable non-small cell lung cancer in a tertiary care centre. A prospective analysis was Methods: carried out on non-metastatic locoregionally advanced non-small cell lung cancer patients who were treated in the Radiotherapy Department, Medical College, Kolkata from January 2014 to July 2015. The patients received concurrent chemoradiotherapy with weekly paclitaxel. Out of 54 patients Results: analysed, overall response rate was 81.48% and complete response rate was 12.96%. The progression free survival rate at 1 year was 41.30%. Median progression free survival was 10.00 ±0.40 months. The most common toxicities were acute pharyngeal and esophageal toxicity. The toxicity was acceptable and response was Conclusion: comparable with other platinum based concurrent chemoradiation regimens.

A PROSPECTIVE COMPARATIVE STUDY BETWEEN CONCURRENT CHEMO RADIOTHERAPY WITH CISPLATIN AND ETOPOSIDE VERSUS PACLITAXEL AND CARBOPLATIN IN LOCALLY ADVANCED NON SMALL CELL LUNG CARCINOMA

Background-The current standard of treatment for unresectable locally advanced Non-small cell lung carcinoma is radiation with concurrent platinum based doublet chemotherapy. But there remains considerable debate over the optimal concurrent regimen , with some advocating Cisplatin-Etoposide , others prefer carboplatin-paclitaxel as an equally effective and better tolerable concurrent regimen.. With this background, our study was aimed at comparing loco-regional control and toxicity prole between these two regimens. Material And Methods- Locally advanced non-metastatic Non-small cell lung carcinoma patients were randomized in two groups- study group received External beam radiotherapy(60Gy/30 fractions/6 weeks) in conventional fractionation along with concurrent weekly chemotherapy with Inj.paclitaxel (45 mg/m2 ) and Inj. Carboplatin (AUC2 ) and control group received same radiotherapy dose with concurrent Inj.cisplatin (50mg/m2) Day 1,8,29,36 and Inj.Etoposide (50 mg/m2) Day 1-5 and Day 29-33. After treatment completion , Locoregional Tumor response was assessed . Patients were evaluated weekly for acute toxicity during radiation therapy, then once at 6-8 weeks after completion of treatment and thereafter every three months for at least 6 months. Results- Overall treatment Response in Study Arm was higher than control arm (73% vs 70%). Complete response rate was also higher in study arm (40% vs 30%) though these differences were not statistically signicant [p value 0.701]. Although statistically not signicant ,Grade III haematological toxicity was less (3% vs 6%) in study arm .Other toxicity proles including acute lung, esophageal and skin toxicities are comparable in both the arms of the study. Conclusion- Concurrent chemo- radiotherapy with cisplatin -etoposide versus paclitaxel -carboplatin in locally advanced NSCLC are comparable in terms of loco-regional control and acute toxicity.

Acute and Late Esophageal Toxicity After SABR to Thoracic Tumors Near or Abutting the Esophagus

Our purpose was to evaluate the incidence of acute and late esophageal toxicity in patients with thoracic tumors near or abutting the esophagus treated with SABR. Among patients with thoracic tumors treated with SABR, we identified those with tumors near or abutting the esophagus. Using the linear-quadratic model with an α/ß ratio of 10, we determined the correlation between dosimetric parameters and esophageal toxicity graded using the Common Terminology Criteria for Adverse Events, version 5.0. Out of 2200 patients treated with thoracic SABR, 767 patients were analyzable for esophageal dosimetry. We identified 55 patients with tumors near the esophagus (52 evaluable for esophagitis grade) and 28 with planning target volume (PTV) overlapping the esophagus. Dose gradients across the esophagus were consistently sharp. Median follow-up and overall survival were 16 and 23 months, respectively. Thirteen patients (25%) developed temporary grade 2 acute esophageal toxicity, 11 (85%) of whom had PTV overlapping the esophagus. Symptoms resolved within 1 to 3 months in 12 patients and 6 months in all patients. No grade 3 to 5 toxicity was observed. Only 3 patients (6%) developed late or persistent grade 2 dysphagia or dyspepsia of uncertain relationship to SABR. The cumulative incidence of acute esophagitis was 15% and 25% at 14 and 60 days, respectively. Acute toxicity correlated on univariate analysis with esophageal Dmax, D1cc, D2cc, Dmax/Dprescription, and whether the PTV was overlapping the esophagus. Esophageal Dmax (BED10) <62 Gy, D1cc (BED10) <48 Gy, D2cc (BED10) <43 Gy, and Dmax/Dprescription <85% were associated with <20% risk of grade 2 acute esophagitis. Only 2 local recurrences occurred. Although 25% of patients with tumors near the esophagus developed acute esophagitis (39% of those with PTV overlapping the esophagus), these toxicities were all grade 2 and all temporary. This suggests the safety and efficacy of thoracic SABR for tumors near or abutting the esophagus when treating with high conformity and sharp dose gradients.

Radiation-Induced Toxicity Risks in Photon Versus Proton Therapy for Synchronous Bilateral Breast Cancer.

PurposeThis study compares photon and proton therapy plans for patients with synchronous bilateral early breast cancer and estimates risks of early and late radiation-induced toxicities.Materials and MethodsTwenty-four patients with synchronous bilateral early breast cancer receiving adjuvant radiation therapy using photons, 3-dimensional conformal radiation therapy or volumetric modulated arc therapy, were included and competing pencil beam scanning proton therapy plans were created. Risks of dermatitis, pneumonitis, acute esophageal toxicity, lung and breast fibrosis, hypothyroidism, secondary lung and esophageal cancer and coronary artery events were estimated using published dose-response relationships and normal tissue complication probability (NTCP) models.ResultsThe primary clinical target volume V95% and/or nodal clinical target volume V90% were less than 95% in 17 photon therapy plans and none of the proton plans. Median NTCP of radiation dermatitis ≥ grade 2 was 18.3% (range, 5.4-41.7) with photon therapy and 58.4% (range, 31.4-69.7) with proton therapy. Median excess absolute risk (EAR) of secondary lung cancer at age 80 for current and former smokers was 4.8% (range, 0.0-17.0) using photons and 2.7% (range, 0.0-13.6) using protons. Median EAR of coronary event at age 80, assuming all patients have preexisting cardiac risk factors, was 1.0% (range, 0.0-5.6) with photons and 0.2% (range, 0.0-1.3) with protons.ConclusionProton therapy plans improved target coverage and reduced risk of coronary artery event and secondary lung cancer while increasing the risk of radiation dermatitis.

69-Year Old Man With Dysphagia and Nasal Regurgitation

69-Year Old Man With Dysphagia and Nasal Regurgitation

A Comparison of Hypofractionated and Twice Daily Thoracic Irradiation in Limited-Stage Small Cell Lung Cancer: An Overlap Weighted Analysis

Despite evidence for the superiority of twice daily (BID) radiotherapy schedules, their utilization in practice remains logistically challenging. Hypofractionation (HFRT) is a commonly implemented alternative. We aim to compare the outcomes and toxicities in limited stage small cell lung cancer (LS-SCLC) patients treated with hypofractionated versus BID schedules.A bi-institutional retrospective cohort review was conducted of LS-SCLC patients treated with BID (45Gy/30 fractions) or HFRT (40Gy/15 fractions) schedules from 2007-2019. Overlap weighting using propensity scores were performed to balance observed covariates between the two radiotherapy schedule groups. Effect estimates of radiotherapy schedule on overall survival (OS), locoregional recurrence (LRR) risk, thoracic response, any grade 3+ (including lung, and esophageal) toxicity were determined using multivariable regression modelling. E-values were used to assess the sensitivity of effect estimate to unobserved confounding.A total of 173 patients were included in the overlap weighted analysis, with 110 patients having received BID treatment, and 63 treated by HFRT. The 5-year OS for the overlap weighted cohort was 24.3% (95% CI, 16.1-36.6), and specifically 22.1% (95% CI, 12.7-38.5) and 26.6% (95% CI, 14.4-49.0%) when stratified by BID and HFRT cohorts specifically. The 5-year LRR risk for the same cohorts after overlap weighting were 68.9% (95% CI, 59.2-80.1), 68.9% (95% CI, 56.6-83.8), and 69.2% (95% CI, 55.3-86.6), respectively. Multivariable regression modelling did not reveal any significant differences in OS (hazard ratio [HR] 1.67, P = 0.38), LRR risk (HR 1.48, P = 0.38), CRT response (odds ratio [OR] 0.23, P = 0.21), any grade 3+ toxicity (OR 1.67, P = 0.33), grade 3+ pneumonitis (OR 1.14, P = 0.84), or grade 3+ esophagitis (OR 1.41, P = 0.62). These effect estimates were consistent between unweighted and overlap weighted cohorts.HFRT, in comparison to BID radiotherapy schedules, does not appear to result in significantly different survival, locoregional control, or toxicity outcomes.

Late Effects of Craniospinal Irradiation Using Electron Spinal Fields for Pediatric Patients

<h3>Purpose/Objective(s)</h3> Craniospinal irradiation (CSI) with photons is associated with significant toxicities. The use of electrons for spinal fields is hypothesized to spare anterior structures but its long-term effects remain poorly characterized. We studied late effects of CSI using electrons for spinal radiotherapy (RT). <h3>Materials/Methods</h3> Records of 84 consecutive patients treated with CSI using electrons for the spine at a single institution from 1983-2014 were reviewed. Median age at RT was 5 (range, 1-14) years with 60% male. Most common histologies were medulloblastoma/PNET (59%) and ependymoma (8%). Most commonly used electron energies were 16 (44%) and 20 (25%) MeV (range, 12-21). Median prescribed dose to the entire spine was 30 (range 6-45) Gy. A spinal boost was used in 14%. A subset of 47 (56%) patients was analyzed for late effects with the following inclusion criteria: 1) age between 2 and 14 years at time of CSI, and 2) clinical and radiographic follow-up for ≥ 5 years. Height <b>z</b>-scores adjusted for age before and after CSI were assessed using CDC stature-for-age charts and compared with a <b>t</b>-test. A Cobb angle of > 10° was used to identify scoliosis. <h3>Results</h3> At a median follow-up of 18 (range, 0-37) years, the median survival was 22 (95% confidence interval [CI], 12-28) years with 50 patients (60%) alive at last follow up. On subset analysis for late effects, 18 (38%) patients developed hypothyroidism and 4 (9%) developed secondary malignancies possibly attributable to spine RT (3 papillary thyroid cancer, 1 renal cell carcinoma) at a median 26 (range, 10-33) years after RT. Chronic pulmonary issues were seen in 2 patients (restrictive lung disease, recurrent pneumonia) and 1 patient developed esophageal strictures and periaortic hemorrhage. No patients developed myelopathy or cardiotoxicity. Median height <b>z</b>-score prior to treatment was -0.3 (37^th percentile; interquartile range [IQR], -1.0 to +0.1) and at last follow up after RT was -2.2 (1^st percentile; IQR, -3.1 to -1.5; <b>P</b> < 0.001). Of 42 patients with spinal curvature assessments, 14 (33%) had scoliosis with median Cobb angle 16° (IQR, 14-18°). <h3>Conclusion</h3> Long-term follow-up of children treated with CSI using electron spinal fields showed frequent musculoskeletal toxicity, predominantly decreased height. Scoliosis and hypothyroidism were seen in at least a third of long-term survivors. Esophageal, pulmonary, cardiac and spinal cord toxicities were infrequent.

ES11.02 Advances in Thoracic Radiation in SCLC

ES11.02 Advances in Thoracic Radiation in SCLC

Comparison of dose volumetric parameters of oesophagus in the radiation treatment of carcinoma breast with and without oesophagus delineation

Abstract Aim: There are only limited studies available in literature that discuss methods to reduce the oesophageal dose and acute oesophagitis during breast cancer radiotherapy. The aim of this study is to compare dose volumetric parameters of oesophagus in radiation treatment of breast with and without oesophagus delineation. Methods: Treatment plans of 44 patients, who underwent chest wall and supraclavicular fossa irradiation, were selected for the study. Oesophagus was later delineated and treatment replanned using three-dimensional conformal radiotherapy (3DCRT) considering oesophagus as an organ at risk (OAR). The dose prescribed was 40 Gy/15 fractions to the planning target volume (PTV). Dose volumetric parameters of oesophagus such as maximum dose (Dmax), mean dose (Dmean), the percentage of oesophagus volume receiving ≥15Gy (V15), ≥25Gy(V25), ≥33Gy(V33) and ipsilateral lung volume parameters V4, V8 and V16 were compared with already executed plans in which oesophagus was not delineated. Results: Contouring the oesophagus as an OAR as a part of the radiotherapy treatment for Carcinoma Breast resulted in statistically significant reduction in dose to the oesophagus. No statistically significant change was found in the ipsilateral lung volume parameters. No compromise in plan quality was required as evident from the statistically non-significant differences in Homogeneity index and Conformity index. Findings: 3DCRT planning with oesophagus delineation can be considered as a method to reduce oesophageal dose and the acute oesophageal toxicity during radiotherapy for carcinoma breast.

Duration of acute esophageal toxicity in concomitant radio-chemotherapy for non-small cell lung cancer with different fractionation schedules.

In our previous prospective trial on accelerated hypofractionated concomitant radiochemotherapy (AHRT-CHT) for non-small-cell lung cancer (NSCLC), the incidence of grade ≥3 acute esophageal toxicity (AET) was similar to that reported for conventionally fractionated concomitant radiochemotherapy (CFRT-CHT), but its duration was prolonged. Thus, we aimed to compare the duration of grade ≥3 AET between AHRT-CHT and CFRT-CHT. Clinical data of 76 NSCLC patients treated with CFRT-CHT (60-66 Gy/2 Gy) during 2015-2020 were retrospectively compared with the data of 92 patients treated with AHRT-CHT (58.8 Gy/2.8 Gy) in the prospective trial. The maximum grade of AET, incidence, and duration of grade ≥3 AET were the end points. Univariate and multivariate analyses were applied to correlate clinical and treatment variables with these end points. Neither the maximum grade of AET (p = 0.71), nor the incidence of grade ≥3 AET (p = 0.87) differed between the two groups. The number of CHT cycles delivered (2 vs 1, p = 0.005) and higher esophagus mean BED (p = 0.009) were significant predictors for a higher maximum grade of AET; older age was a significant predictor for higher incidence of grade ≥3 AET (p = 0.03). The median duration of grade ≥3 AET in AHRT-CHT and CFRT-CHT group was 30 days (range 5-150) vs 7 days (range 3-20), respectively, p = 0.0005. In multivariate analysis, only the AHRT-CHT schedule (p=0.003) was a significant predictor for a longer duration of grade ≥3 AET. Despite similar incidence of grade ≥3 AET, its duration is significantly prolonged in NSCLC patients treated with AHRT-CHT compared to CFRT-CHT. Reporting only the rate of grade ≥3 AET in clinical trials may underestimate the real extent of the esophageal toxicity; its duration should also be routinely reported.

Post-operative radiation therapy for non-small cell lung cancer: A comparison of radiation therapy techniques

ObjectivesPost-operative radiation therapy (PORT) in locally advanced non-small cell lung cancer (LA-NSCLC) has historically been associated with toxicity. Conformal techniques like intensity modulated radiation therapy (IMRT) have the potential to reduce acute and long-term toxicity from radiation therapy. Among patients receiving PORT for LA-NSCLC, we identified factors associated with receipt of IMRT and evaluated the association between IMRT and toxicity. MethodsWe queried the Surveillance, Epidemiology, and End Results (SEER)-Medicare database between January 1, 2006 to December 31, 2014 to identify patients diagnosed with Stage II or III NSCLC and who received upfront surgery and subsequent PORT. Baseline differences between patients receiving 3-dimentional conformal radiation therapy (3D-CRT) and IMRT were assessed using the chi-squared test for proportions and the t-test for means. Multivariable logistic regression was used to identify predictors of receipt of IMRT and pulmonary, esophageal, and cardiac toxicity. Propensity-score matching was employed to reduce the effect of known confounders. ResultsA total of 620 patients met the inclusion criteria, among whom 441 (71.2%) received 3D-CRT and 179 (28.8%) received IMRT. The mean age of the cohort was 73.9 years and 54.7% were male. The proportion of patients receiving IMRT increased from 6.2% in 2006 to 41.4% in 2014 (P < 0.001). IMRT was not associated with decreased pulmonary (OR 0.89; 95% CI, 0.62–1.29), esophageal (OR 1.09; 95% CI, 0.0.75–1.58), or cardiac toxicity (OR 1.02; 95% CI, 0.69–1.51). These findings held on propensity-score matching. Clinical risk factors including comorbidity and prior treatment history were associated with treatment toxicity. ConclusionIn a cohort of elderly patients, the use of IMRT in the setting of PORT for LA-NSCLC was not associated with a difference in toxicity compared to 3D-CRT. This finding suggests that outcomes from PORT may be independent of radiotherapy treatment technique.

PO-1176 Duration of acute esophageal toxicity in RT-CHT for NSCLC with different fractionation schedules

PO-1176 Duration of acute esophageal toxicity in RT-CHT for NSCLC with different fractionation schedules

Prevention and management of acute esophageal toxicity during concomitant chemoradiotherapy for locally advanced lung cancer.

Standard treatment for locally advanced non-small cell lung cancer (LA-NSCLC) is concomitant chemoradiotherapy. The survival benefit of combined treatment is partially counterbalanced by an increased rate of acute esophageal toxicity. Several pharmaceutical products are available for prevention and management of esophagitis, including Faringel Plus. To assess the incidence and the grade, identify the correlations with clinical, dosimetric, and therapeutic variables, and analyse the role of Faringel Plus as a pharmaceutical preventive measure against acute esophageal toxicity. Patients with LA-NSCLC treated with concomitant radiochemotherapy were retrospectively reviewed. Acute esophagitis and dysphagia were graded according to Common Terminology Criteria for Adverse Events version 5.0. Clinical, dosimetric, and therapeutic correlations were investigated using χ2 test. Among the 23 analysed patients, 18 (78.3%) and 1 (4.3%) developed G2 and G3 esophagitis, respectively; G1-2 dysphagia were reported in 11 cases (47.8%). No statistically significant correlation between the variables considered and acute esophageal toxicity was identified. In the group of patients who received Faringel Plus as preventive treatment (10 subjects, 43.5%), dysphagia presentation time was significantly longer (p = 0.038); esophagitis onset time was longer and symptoms duration was shorter. Faringel Plus allowed a reduction in the use of analgesic drugs. Acute mild esophageal toxicity was confirmed to be a common side effect in this setting. No clinical-dosimetric parameter has been demonstrated to be effective in predicting acute esophageal toxicity. The use of Faringel Plus appears effective as a therapeutic and prophylactic tool to manage acute esophageal toxicity.

A Comparison of Hypofractionated and Twice-Daily Thoracic Irradiation in Limited-Stage Small-Cell Lung Cancer: An Overlap-Weighted Analysis.

Simple SummaryThe optimal thoracic radiotherapy schedule for limited-stage small cell lung cancer (LS-SCLC) patients remains controversial. We conducted a propensity score adjusted analysis of LS-SCLC patients treated at our institutions with 40Gy/15 fractions versus 45Gy/30 twice daily. After overlap weighting for clinical and treatment variables and attaining good balance, we did not find a significant difference in overall survival, locoregional recurrence risk, thoracic response, or ≥grade 3 toxicity. Moderate hypofractionation, with its similar outcomes and logistical advantages, may present a reasonable alternative to twice daily radiotherapy.Despite evidence for the superiority of twice-daily (BID) radiotherapy schedules, their utilization in practice remains logistically challenging. Hypofractionation (HFRT) is a commonly implemented alternative. We aim to compare the outcomes and toxicities in limited-stage small-cell lung cancer (LS-SCLC) patients treated with hypofractionated versus BID schedules. A bi-institutional retrospective cohort review was conducted of LS-SCLC patients treated with BID (45 Gy/30 fractions) or HFRT (40 Gy/15 fractions) schedules from 2007 to 2019. Overlap weighting using propensity scores was performed to balance observed covariates between the two radiotherapy schedule groups. Effect estimates of radiotherapy schedule on overall survival (OS), locoregional recurrence (LRR) risk, thoracic response, any ≥grade 3 (including lung, and esophageal) toxicity were determined using multivariable regression modelling. A total of 173 patients were included in the overlap-weighted analysis, with 110 patients having received BID treatment, and 63 treated by HFRT. The median follow-up was 20.4 months. Multivariable regression modelling did not reveal any significant differences in OS (hazard ratio [HR] 1.67, p = 0.38), LRR risk (HR 1.48, p = 0.38), thoracic response (odds ratio [OR] 0.23, p = 0.21), any ≥grade 3+ toxicity (OR 1.67, p = 0.33), ≥grade 3 pneumonitis (OR 1.14, p = 0.84), or ≥grade 3 esophagitis (OR 1.41, p = 0.62). HFRT, in comparison to BID radiotherapy schedules, does not appear to result in significantly different survival, locoregional control, or toxicity outcomes.

Twice-daily chemoradiotherapy in limited-stage small-cell lung cancer

Acute radiation-induced oesophagitis has been associated with adverse events such as weight loss, substantial effect on quality of life, and reduced survival.1 Concurrent chemotherapy given with hyperfractionated radiation therapy has been associated with an increased incidence of acute oesophageal toxicity.2 Several dosimetric parameters and high doses have been associated with an increased risk of acute oesophagitis.1 However, radiotherapy technical developments (eg, use of intensity-modulated radiotherapy and omission of elective nodal irradiation) allow a reduced dose to the organs at risk, including the oesophagus.

Efficacy and cost of high-frequency IGRT in elderly stage III non-small-cell lung cancer patients

BackgroundHigh-frequency image-guided radiotherapy (hfIGRT) is ubiquitous but its benefits are unproven. We examined the cost effectiveness of hfIGRT in stage III non-small-cell lung cancer (NSCLC).MethodsWe selected stage III NSCLC patients ≥66 years old who received definitive radiation therapy from the Surveillance, Epidemiology, and End-Results-Medicare database. Patients were stratified by use of hfIGRT using Medicare claims. Predictors for hfIGRT were calculated using a logistic model. The impact of hfIGRT on lung toxicity free survival (LTFS), esophageal toxicity free survival (ETFS), cancer-specific survival (CSS), overall survival (OS), and cost of treatment was calculated using Cox regressions, propensity score matching, and bootstrap methods.ResultsOf the 4,430 patients in our cohort, 963 (22%) received hfIGRT and 3,468 (78%) did not. By 2011, 49% of patients were receiving hfIGRT. Predictors of hfIGRT use included treatment with intensity-modulated radiotherapy (IMRT) (OR = 7.5, p < 0.01), recent diagnosis (OR = 51 in 2011 versus 2006, p < 0.01), and residence in regions where the Medicare intermediary allowed IMRT (OR = 1.50, p < 0.01). hfIGRT had no impact on LTFS (HR 0.97; 95% CI 0.86–1.09), ETFS (HR 1.05; 95% CI 0.93–1.18), CSS (HR 0.94; 95% CI 0.84–1.04), or OS (HR 0.95; 95% CI 0.87–1.04). Mean radiotherapy and total medical costs six months after diagnosis were $17,330 versus $15,024 (p < 0.01) and $71,569 versus $69,693 (p = 0.49), respectively.ConclusionhfIGRT did not affect clinical outcomes in elderly patients with stage III NSCLC but did increase radiation cost. hfIGRT deserves further scrutiny through a randomized controlled trial.

A Prospective Open‐Label Observational Study of a Buffered Soluble 70 mg Alendronate Effervescent Tablet on Upper Gastrointestinal Safety and Medication Errors: The GastroPASS Study

ABSTRACTUpper gastrointestinal (GI) side effects are a main reason for discontinuing bisphosphonate treatment, an important therapeutic option for osteoporosis patients. Consequently, the development of novel formulations with improved tolerability is warranted. In this multicenter prospective, observational, postauthorization safety study conducted in Italy and Spain, postmenopausal women (PMW) with osteoporosis (naïve to bisphosphonates) were treated weekly with a buffered soluble alendronate 70 mg effervescent (ALN‐EFF) tablet (Binosto®) and followed for 12 ± 3 months. Information was collected on adverse events (AEs), medication errors, persistence, and compliance using the Morisky‐Green questionnaire. Patients (N = 1028) aged 67 ± 9 years (mean ± SD) received ALN‐EFF weekly. The cumulative incidence of upper GI AEs (oesophageal toxicity, gastritis, gastric ulcers, and duodenitis) related to ALN‐EFF (primary endpoint) was 9.6% (95% confidence interval [CI] 7.9–11.6%), the vast majority being of mild intensity. The most frequently occurring upper GI AEs related to ALN‐EFF were dyspepsia (2.7%), gastroesophageal reflux disease (2.4%), and nausea (2.2%). None of the relevant upper GI AEs listed in the primary endpoint and no serious AEs were reported. At least one medication error occurred in 29.9% (95% CI 27.1–32.8%) of patients. However, the majority of medication errors were associated with administration instructions applicable to any oral bisphosphonate and only seven medication errors were associated with the ALN‐EFF formulation. ALN‐EFF was discontinued in 209 of 1028 (20.3%) patients. The most frequent reasons for discontinuation were AEs related to ALN‐EFF (46.9%) and patients' decision (42.6%). Compliance with ALN‐EFF was high, reflected by a mean Morisky‐Green score of 92.8 ± 18.6. PMW with osteoporosis treated with ALN‐EFF in a real‐world setting experienced few upper GI AEs. In addition, they had a low discontinuation and high compliance compared with other formulations, suggesting that ALN‐EFF may increase patient satisfaction and therefore long‐term adherence and efficacy. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

The effect of ochratoxin A on cytotoxicity and glucose metabolism in human esophageal epithelium Het-1A cells

Ochratoxin A (OTA) is a widespread mycotoxin worldwide that causes major health risks. The esophageal epithelium is unavoidably exposed to food contaminated OTA after ingestion. Yet, few studies have involved in the putative effects of OTA on the cytotoxicity and glucose metabolism responses on esophageal epithelial cells. In this in vitro study, we aimed to investigate the effects of OTA on esophageal epithelial cell intracellular apoptosis, oxidative stress, DNA damage, mitochondrial function and glucose metabolism. Human esophageal epithelial Het-1A cells were exposed to 2.5, 5 or 10 μM OTA for 24 h. The results showed that OTA decreased cell viability and concomitantly increased apoptosis-related indices, reactive oxygen species generation, oxidative DNA damage, mitochondrial dysfunction and mitochondrial apoptotic pathway activation. In addition, OTA switched the glucose metabolism of Het-1A cells from oxidative phosphorylation towards glycolysis by decreasing the expression of tricarboxylic acid cycle-associated enzymes such as α-ketoglutarate dehydrogenase and isocitrate dehydrogenase 1 and by increasing pyruvate dehydrogenase kinase 1 expression. The data indicated that cell apoptosis, oxidative damage, mitochondrial dysfunction and glucose metabolism perturbation might play pivotal roles in the mechanism of OTA-induced esophageal toxicity.

Short Communication: Interim toxicity analysis for patients with limited stage small cell lung cancer (LSCLC) treated on CALGB 30610 (Alliance) / RTOG 0538

IntroductionThe CALGB 30610/RTOG 0538 randomized trial was designed to test whether high-dose thoracic radiotherapy (TRT) would improve survival compared with 45 Gy twice-daily (BID) TRT in limited stage small cell lung cancer (LSCLC). Two piloted experimental TRT regimens were of interest to study, 70 Gy daily (QD) and 61.2 Gy concomitant boost (CB). Driven by concerns about adequate patient accrual, a study design was employed that eliminated one experimental TRT arm based on early interim toxicity and tolerability, with the study then continuing as a traditional 2-arm phase III study. MethodsPatients with LSCLC were assigned to receive four cycles of cisplatin and etoposide chemotherapy with one of 3 TRT regimens starting with either the first or second cycle of chemotherapy. The interim endpoint was the cumulative highest toxicity calculated from a scoring system based on treatment-related grade 3 and higher toxicity and the ability to complete therapy in the experimental arms. ResultsThe final interim analysis was performed after 70 patients accrued to each experimental cohort, and a difference in treatment related toxicity scoring was not found (p = 0.739). Severe esophageal toxicity was comparable in both cohorts. Pulmonary toxicity was low overall, though 4 patients (5.7 %) on the 61.2 Gy arm developed grade 4 dyspnea, which was not observed in the 70 Gy arm. A protocol mandated decision was made to discontinue the 61.2 Gy arm following review of toxicity with the Data and Safety Monitoring Board. ConclusionA randomized trial design using a planned early interim toxicity analysis to discriminate between experimental treatment arms is feasible in a phase III setting. Refinement of the design could increase the likelihood of detecting clinically meaningful differences in toxicity in future studies.

Olaparib increases the therapeutic index of hemithoracic irradiation compared with hemithoracic irradiation alone in a mouse lung cancer model

BackgroundThe radiosensitising effect of the poly(ADP-ribose) polymerase inhibitor olaparib on tumours has been reported. However, its effect on normal tissues in combination with radiation has not been well studied. Herein, we investigated the therapeutic index of olaparib combined with hemithoracic radiation in a urethane-induced mouse lung cancer model.MethodsTo assess tolerability, A/J mice were treated with olaparib plus whole thorax radiation (13 Gy), body weight changes were monitored and normal tissue effects were assessed by histology. In anti-tumour (intervention) studies, A/J mice were injected with urethane to induce lung tumours, and were then treated with olaparib alone, left thorax radiation alone or the combination of olaparib plus left thorax radiation at 8 weeks (early intervention) or 18 weeks (late intervention) after urethane injection. Anti-tumour efficacy and normal tissue effects were assessed by visual inspection, magnetic resonance imaging and histology.ResultsEnhanced body weight loss and oesophageal toxicity were observed when olaparib was combined with whole thorax but not hemithorax radiation. In both the early and late intervention studies, olaparib increased the anti-tumour effects of hemithoracic irradiation without increasing lung toxicity.ConclusionsThe addition of olaparib increased the therapeutic index of hemithoracic radiation in a mouse model of lung cancer.