Treatment-related Toxicity In Patients Research Articles

Predictive factors of severe early treatment-related toxicity in patients receiving first-line treatment for metastatic colorectal cancer: Pooled analysis of 2190 patients enrolled in Fédération Francophone de Cancérologie Digestive (FFCD) trials

AimFew studies have explored the association between baseline characteristics and the occurrence of early toxicities in patients treated with first-line chemotherapy for metastatic colorectal cancer (mCRC). Patients and methodsIndividual patient data of 2190 patients enrolled in 10 prospective FFCD (Fédération Francophone de Cancérologie Digestive) trials were analysed. Severe early toxicity was defined as the occurrence of grade ≥III toxicity within 3 months after initiation of chemotherapy (ET3). ResultsPatients received monotherapy based on 5-FU (n = 1068), a cytotoxic doublet (n = 395) or tritherapy with a cytotoxic doublet plus anti-VEGF agent or a cytotoxic triplet (n = 727). The patients received 5-FU (100%), Irinotecan (39.6%), Oxaliplatin (13.4%), Bevacizumab (29.6%) or Aflibercept (1.8%). ET3 occurred in 244 patients (22.8%) with monotherapy, 248 patients (62.8%) with doublet and 392 patients (53.9%) with tritherapy. The most frequent ET3s were related to biological abnormalities and/or gastrointestinal, general and vascular disorders. The prognostic factors for the occurrence of an ET3 in multivariate analysis were a performance status of 2 rather than 0–1 (OR 2.57; 95% CI [1.16, 5.73]; p = 0.02), tritherapy versus monotherapy (OR 2.31; 95% CI [0.84, 6.33]; p = 0.02), alkaline phosphatase > 300 UI/l (OR 3.07; 95% CI [1.79, 5.27]; p < 0.001) and non-resected primary tumour versus resection (OR 1.59; 95% CI [1.06, 2.39]; p = 0.02). Median overall survival in patients without ET3 was significantly longer than that in patients with ET3 (HR 0.87; 95% CI [0.80–0.96]; p = 0.004). ConclusionET3 is frequent whatever the treatment regimen and is associated with certain baseline characteristics. The clinical impact of ET3 on prognosis in mCRC warrants further investigation.

Long-term outcome of 177Lu-PSMA-617 radioligand therapy in heavily pre-treated metastatic castration-resistant prostate cancer patients.

ObjectiveInvestigators have extensively explored the short-term safety and efficacy data on 177Lu-PSMA-617 radioligand therapy (RLT) in mCRPC patients. However, scarce literature is reported on the long-term outcome of these patients. The current goal of this study is focused on the long-term outcome of mCRPC patients treated with 177Lu-PSMA-617 RLT.MethodsAmong 135 patients, 121 mCRPC patients fulfilled the eligibility criteria and were included in the final analysis. Patients received a median of 3 cycles of 177Lu-PSMA-617 RLT at 6 to 12-week intervals. Primary endpoint included overall survival (OS) and secondary endpoints involved progression-free survival (PFS), predictive factors of OS and PFS, PSA response rate, molecular response, clinical response, and toxicity assessment.ResultsThe median administered cumulative activity was 20 GBq (3.7–37 GBq). The median follow-up duration was 36 months (6–72 months). The estimated median PFS and OS were 12 months (mo) (95% CI: 10.3–13 mo) and 16 mo (95% CI: 13–17 mo), respectively. Any PSA decline and PSA decline >50% was achieved in 73% and 61% of the patients, respectively. Multivariate analysis revealed only failure to achieve >50% PSA decline as a significant factor associated with a poor PFS. Prognostic factors associated with reduced OS included, failure to experience >50% PSA decline, heavily pre-treated patient cohort who received >2 lines of prior treatment options, and patient sub-group treated with ≥2 lines of chemotherapy. Patients re-treated with additional treatment options after attaining 177Lu-PSMA refractory disease showed a remarkably prolonged OS. A significant clinical benefit was achieved post 177Lu-PSMA-617 RLT. The most common toxicities observed were fatigue (34.7%), followed by nausea (33%), and dry mouth (24.7%).ConclusionThe current study supports the short-term safety and efficacy results of high response rates, prolonged PFS and OS, improved quality of life, and low treatment-related toxicities in patients treated with 177Lu-PSMA-617 radioligand therapy.

The effect of oral omega-3 polyunsaturated fatty acid supplementation on muscle maintenance and quality of life in patients with cancer: A systematic review and meta-analysis

Omega-3 polyunsaturated fatty acid (PUFA) supplementation has been proposed as a potential therapy for cancer-related malnutrition, which affects up to 70% of patients with cancer. The aim of this systematic review and meta-analysis was to examine the effects of oral omega-3 PUFA supplementation on muscle maintenance, quality of life, body weight and treatment-related toxicities in patients with cancer. Randomised controlled trials in patients with cancer aged ≥18 years were retrieved from 5 electronic databases: MEDLINE (via PubMed), EMBASE, CENTRAL, CINAHL (via EBSCOhost), and Web of Science, from database inception until 31st of December 2019. The quality of included studies was assessed using the Cochrane risk of bias tool. Trials supplementing ≥600mg/d omega-3 PUFA (oral capsules, pure fish oil or oral nutritional supplements) compared with a control intervention for ≥3 weeks were included. Meta-analyses were performed in RevMan to determine the mean differences (MD) in muscle mass, quality of life and body weight, and odds ratio (OR) for the incidence of treatment-related toxicities between omega-3 PUFA and control groups with 95% confidence intervals (CI) and I2 for heterogeneity. We included 31 publications in patients with various types of cancers and degrees of malnutrition. The Cochrane risk of bias tool graded most trials as 'unclear' or 'high' risk of bias. Meta-analyses showed no significant difference between omega-3 PUFA supplements and control intervention on muscle mass, quality of life and body weight. Oral omega-3 PUFA supplements reduced the likelihood of developing chemotherapy-induced peripheral neuropathy (OR: 0.20; 95% CI: 0.10-0.40; p<0.001; I2=0%). This systematic review and meta-analysis indicates that oral omega-3 PUFA supplementation does not improve muscle maintenance, quality of life or body weight in patients with cancer, but may reduce the incidence of chemotherapy-induced peripheral neuropathy. Well-designed large-scale randomised controlled trials in homogenous patient cohorts are required to confirm these findings.

PCN269 Patients and Healthcare Providers Reported Outcomes of an E-Health System (ZEMY) Designed to Manage Symptoms and Treatment-Related Toxicities in Patients with Breast Cancer

PCN269 Patients and Healthcare Providers Reported Outcomes of an E-Health System (ZEMY) Designed to Manage Symptoms and Treatment-Related Toxicities in Patients with Breast Cancer

PCN235 Feasibility Assessment of an E-Health System (ZEMY) Designed to Manage Symptoms and Treatment-Related Toxicities in Patients with Breast Cancer

ZEMY is an e-health system that gathers data from a smartphone application companion and a web platform that supports clinician for telemedicine or face-to-face visits. ZEMY has been developed to improve symptom management and enhance patient and healthcare providers (HCP) interactions. We report here feasibility and devices deficiencies (DD). This was a three-month single arm study conducted at five French sites. Adult women with breast cancer initiating oral and/or parenteral cancer treatment received a smartphone with ZEMY installed and verbal training. Patients started cancer treatment on Day 1 and were followed for three months. The ZEMY software made recommendations to patients on the self-management of ten pre-specified symptoms and transmitted automatic messages to HCP. Primary outcome was patient feasibility response at 3 months using a composite endpoint assessing frequency and quality of patients’ connections. Secondary endpoints were description of Symptom Reported Connections (SRC) and DD. 54 patients were enrolled in the study. 31 patients (57.4%) were responders, not significantly higher than the predefined cut-off of 50% (lower limit of the one-sided 95% CI: 45.3%), despite high response rates of its components: ≥3 completed SRC (87.0%); completed SRC ≥60% (66.0%). 3815 SRC were reported by patients, 2979 automatic recommendations were sent back (mostly related to fatigue, pain, anxiety/depression) and 615 (20.6%) led to a message sent to HCP. 95 DD were reported in 37/54 patients (68.5%). Main reasons were inappropriate recommendations (n=51) and device malfunction (n=36). No adverse device effects were reported. The proof of feasibility of ZEMY was not demonstrated instead of an encouraging rate of its two components and a high number of SRC and recommendations. Feasibility of an e-health system is difficult to anticipate in a formally statistical test due to uncertainty of predefined hypothesis. The DD observed indicates the need for user support.

The predictive value of G8 and the Cancer and aging research group chemotherapy toxicity tool in treatment-related toxicity in older Chinese patients with cancer

IntroductionOlder patients experience a higher risk of treatment-related toxicity (TRT). The G8 screening tool was developed to separate cancer older patients fit to receive standard treatment from those who are frail and experiencing functional decline due to reduced organ function and multiple comorbidities. The Cancer and Aging Research Group chemotherapy toxicity tool (CARG-tt) questionnaire was developed to predict chemotherapy toxicity in geriatric patients. This prospective observational study evaluated the performance of G8 and CARG-tt in predicting severe TRT in older Chinese cancer patients. MethodsChinese patients aged ≥65 with a diagnosis of solid malignancy and scheduled to receive anti-cancer treatment (chemotherapy or targeted therapy) were enrolled from March 2016 to July 2017 at the Department of Clinical Oncology at Queen Mary Hospital in Hong Kong. All patients completed the G8 and CARG-tt screening and pre-treatment assessments before starting treatment. Patients were monitored for any severe TRT, which was defined by grades 3–5 using the National Cancer Institute's Common Terminology Criteria for Adverse Events v4.03, treatment discontinuation, or unexpected hospitalization from starting to 30 days after treatment. ResultsA total of 259 patients (male: 154, 59.5%; median age: 73.4, age range: 65–93) were enrolled in the study. Two hundred and ten (81.1%) patients received chemotherapy while the rest (n = 49, 18.9%) received targeted therapy. Overall, 146 patients (56.8%) experienced severe TRT.The mean G8 score was 12.4 (SD: 2.8). The G8 score had a significant association with unexpected admission (cutoff: 14, 41.3% vs. 26.5%, p = 0.03) but not significant in other types of TRTs. The mean CARG-tt score was 7.67 (SD: 3.7); it was not associated with severe TRTs. ConclusionsThe G8 and CARG-tt demonstrated a weak prediction of severe TRT in older Chinese cancer patients. Future studies need to develop predictive tools for TRT in patients receiving novel antineoplastic therapies, with a focus on subgroup analysis for different populations.

CT and FDG-PET radiologic biomarkers in p16+ oropharyngeal squamous cell carcinoma patients treated with definitive chemoradiotherapy

PurposeTo assess associations between imaging biomarkers from standard of care pre-treatment CT and FDG-PET scans and locoregional (LR) and distant metastatic (DM) recurrences in patients with p16+ oropharyngeal squamous cell carcinoma (OPSCC) treated with definitive chemoradiotherapy (CRT). MethodsAn institutional database from a single NCI-designated cancer center identified 266 patients with p16+ OPSCC treated with definitive CRT in our department from 2005 to 2016 with evaluable pre-treatment FDG-PET scans. Quantitative SUV metrics and qualitative imaging metrics were determined from FDG-PET and CT scans, while clinical characteristics were abstracted from the medical record. Associations between clinical/imaging features and time to LR (TTLRF) or DM (TTDMF) failure and overall survival (OS) were assessed using univariable Cox regression and penalized stepwise regression for multivariable analyses (MVA). ResultsThere were 27 LR and 32 DM recurrences as incident failures. Imaging biomarkers were significantly associated with TTLRF, TTDMF and OS. FDG-PET metrics outperformed CT and clinical metrics for TTLRF, with metabolic tumor volume being the only significant feature selected on MVA: C-index = 0.68 (p = 0.01). Radiographic extranodal extension (rENE), positive retropharyngeal nodes (RPN+), and clinical stage were significant on MVA for TTDMF: C-index = 0.84 (p < 0.001). rENE, group stage, and RPN+ were significant on MVA for OS: C-index = 0.77 (p < 0.001). ConclusionsIn the largest study to date of uniformly treated patients with CRT to evaluate both pretreatment CT and FDG-PET, radiographic biomarkers were significantly associated with TTLRF, TTDMF and OS among patients with p16+ OPSCC treated with CRT. CT metrics performed best to predict TTDMF, while FDG-PET metrics showed improved prediction for LRRFS. These metrics may help identify candidates for treatment intensification or de-escalation of therapy. Statement of translational relevancePre-treatment imaging features from standard-of-care PET/CT imaging show promise for predicting long-term outcomes following HPV-associated oropharynx cancer (HPV-OPC) therapy. This study comprehensively characterizes qualitative and quantitative pre-treatment imaging metrics associated with time to pattern-specific failure in a cohort of 266 patients treated uniformly with definitive chemoradiation. Multivariate analysis (MVA) for time to locoregional failure (TTLRF), time to distant metastatic failure (TTDMF), and overall survival (OS) was performed. FDG-PET metrics outperformed CT and clinical metrics for TTLRF. CT radiographic extranodal extension, positive retropharyngeal nodes, and stage strongly predicted TTDMF (combined C-index = 0.84, log rank p < 0.001). Number of smoking pack-years complemented clinical and imaging features only in patients without radiographic extranodal extension or positive retropharyngeal nodes. Time to pattern-specific failure is important for guiding treatment de-escalation strategies, which intend to reduce treatment-related toxicity in patients with relatively long expected survival times. This study suggests that PET/CT features should play a crucial role in future de-escalation trials and management of HPV-OPC patients.

Toxicities Caused by Head and Neck Cancer Treatments and Their Influence on the Development of Malnutrition: Review of the Literature.

Malnutrition poses a significant problem for oncology patients, resulting in fatalities within this population. Patients with head and neck cancer (HNC) are at high risk, with up to 90% developing malnutrition. Common treatments used for HNC can often lead to adverse side effects, including oral health conditions, gastrointestinal upsets, and several metabolic changes. Consequently, treatments can cause inadequate nutritional intake, resulting in a reduction in energy consumption, and alterations in energy utilization, contributing to the development of malnutrition. Furthermore, the presence of these treatment toxicities, and the related malnutrition can lead to reduced quality of life, weight loss, and psychological distress. There are interventions available (nutritional, medicinal, and physical therapies) that have demonstrated potential effectiveness in reducing the severity of symptomatic toxicities, reducing the risk of malnutrition, and improving survival outcomes of patients with HNC. Based on the findings of this review, there is an urgent need for the implementation or continuation of multi-disciplinary strategies, as well as updated and improved guidelines to assist in the prevention and treatment of malnutrition caused by treatment-related toxicities in patients with HNC.

Salvage I-125 brachytherapy for locally-recurrent prostate cancer after radiotherapy.

Retrospective, single-institution analysis of clinical outcomes and treatment-related toxicity in patients treated with salvage I-125 low-dose rate (LDR) brachytherapy (BT) for locally-recurrent prostate cancer after radiotherapy. Between 2008 and 2018, 30 patients with biopsy-confirmed prostate cancer recurrence underwent salvage treatment with I-125 LDR-BT. Of these 30 patients, 14 were previously treated with primary external beam radiotherapy (EBRT; median dose, 73 Gy) and 16 with primary I-125 LDR-BT (145 Gy and 160 Gy in 14 and 2 cases, respectively). At seed implantation, the mean age was 75.8 years, with a median Gleason score of 7 and pre-salvage PSA of <10 ng/mL. Six patients received androgen deprivation therapy for six months after relapse diagnosis. The prescribed salvage I-125 BT dose to the gland was 120-130 Gy, with dose restrictions of Dmax <135% (urethra) and <100% (rectum). Toxicity was evaluated according to the CTCAE scale (v4.0). At a median follow-up of 45 months, the biochemical recurrence-free survival rates at 1, 3 and 5 years were 86.7%, 56.7% and 53.3%, respectively. Overall survival at 5 years was 87%. On the multivariate analysis, two variables were significant predictors of recurrence: PSA at relapse and nadir PSA post-salvage. Grade 3 genitourinary toxicity was observed in 5 patients (radiation-induced cystitis in 3 cases and urethral stenosis in 2) and G3 gastrointestinal toxicity in 3 patients (rectal bleeding). Salvage therapy with I-125 brachytherapy is a safe and effective treatment option for locally-recurrent prostate cancer in previously-irradiated patients. High pre-salvage PSA and post-salvage nadir PSA values were significantly associated with a worse disease control after salvage I-125 LDR-BT. In well-selected patients, I-125 LDR-BT is comparable to other salvage therapies in terms of disease control and toxicity. However, more research is needed to determine the optimal management of locally-recurrent prostate cancer.

Long-term outcomes and safety after reirradiation in locally recurrent nasopharyngeal carcinoma in anon-endemic area.

To determine outcomes and toxicities after reirradiation for locally recurrent nasopharyngeal carcinoma (rNPC) and to apply aprognostic index in anon-endemic region. We retrospectively reported progression-free survival (PFS), overall survival (OS), and treatment-related toxicities in patients treated with curative intent for locally rNPC. We applied the prognostic model for OS and grade5 radiotherapy (RT)-related toxicities published by Li etal. and evaluated its prognostic accuracy by receiver operating characteristic (ROC) curve analysis. Between 2005 and 2018, 33patients were treated for rNPC in our institution. Median follow-up was 60months. The mean time to local recurrence was 75months. Six (18%) patients had apersistent grade3 toxicity from aprevious RT course. The median re-RT dose was 66 Gy. After re-RT, 13patients had local failure and 3patients had metastatic recurrence. Median PFS was 18months with a5-year PFS rate of 29%. Median OS was 35months with a5-year OS rate of 37%. Grade3 or higher toxicities rate was 74%. There were 21% grade5 toxicities. The median time to agrade5 toxicity was less than 6months following re-RT. The prognostic nomogram was not predictive for OS or grade5 toxicities. Reirradiation of rNPC is an effective treatment but is associated with ahigh rate of life-threatening toxicity. Stratification of patients based on their risk of developing severe toxicity is needed to select patients who will most likely benefit from re-RT.

A review of Image Guided Radiation Therapy in head and neck cancer from 2009-201 - Best Practice Recommendations for RTTs in the Clinic.

Radiation therapy (RT) is beneficial in Head and Neck Cancer (HNC) in both the definitive and adjuvant setting. Highly complex and conformal planning techniques are becoming standard practice in delivering increased doses in HNC. A sharp falloff in dose outside the high dose area is characteristic of highly complex techniques and geometric uncertainties must be minimised to prevent under dosage of the target volume and possible over dosage of surrounding critical structures. CTV-PTV margins are employed to account for geometric uncertainties such as set up errors and both interfraction and intrafraction motion. Robust immobilisation and Image Guided Radiation Therapy (IGRT) is also essential in this group of patients to minimise discrepancies in patient position during the treatment course. IGRT has evolved with increased 2-Dimensional (2D) and 3-Dimensional (3D) IGRT modalities available for geometric verification. 2D and 3D IGRT modalities are both beneficial in geometric verification while 3D imaging is a valuable tool in assessing volumetric changes that may have dosimetric consequences for this group of patients. IGRT if executed effectively and efficiently provides clinicians with confidence to reduce CTV-PTV margins thus limiting treatment related toxicities in patients. Accumulated exposure dose from IGRT vary considerably and may be incorporated into the treatment plan to avoid excess dose. However, there are considerable variations in the application of IGRT in RT practice. This paper aims to summarise the advances in IGRT in HNC treatment and provide clinics with recommendations for an IGRT strategy for HNC in the clinic.

Interventional multicenter study to assess the feasibility of an e-health system (ZEMY) designed to manage symptoms and treatment-related toxicities in patients with breast cancer.

e14107 Background: There is increasing interest in using e-health systems for symptom monitoring and alert triggering. ZEMY, a new software medical device, was developed to improve symptom management and enhance patient and health care team interactions. Methods: This was a three-month open-label, interventional, single arm study conducted at five French sites. Adult women with breast cancer (BC) initiating oral and/or parenteral cancer treatment received a smartphone with ZEMY installed and verbal training. Patients started cancer treatment on Day 1 and were followed for three months. Patients entered data for ten prespecified symptoms. The ZEMY software made recommendations to patients on the self-management of symptoms and transmitted automatic messages to the health care team. Primary outcome was patient feasibility response at 3 months (completion of ≥3 symptom reports and a report completion rate of ≥60% per patient). Secondary objectives included ZEMY symptom management, usability and satisfaction, and device deficiencies (DDs). Results: Overall, 54 patients were enrolled (Jun 2018 to Jan 2019) and 52 (96.3%) completed the study. Thirty-one (57.4%) patients were responders; this was not significantly higher than the predefined cut-off and ZEMY feasibility was not demonstrated. Forty-seven (87.0%) patients had ≥3 completed symptom reports and 33 (66.0%) patients had a report completion rate of ≥60% (missing: n = 4). In subgroup analyses, 22/30 (73.3%) patients with locally advanced BC and 24/36 (66.7%) patients aged 40–60 years were responders. ZEMY patient recommendations and health care team automatic messages were considered relevant at least once in &gt; 74% of cases for five of the six symptoms that were reported at least once by more than 1/3 of patients (diarrhea, nausea, fatigue, cutaneous and mucosal toxicities, and anxiety/depression). Using a 0–10 visual analogue scale, mean ZEMY satisfaction score was higher for patients than investigators (6.3 ±2.9 vs 4.4 ±1.5). Overall, 95 DDs were reported in 37 (68.5%) patients. Main reasons for DDs were inappropriate recommendations (n = 51) and device malfunction (n = 36). Conclusions: The primary endpoint of the study was not reached; however, higher response rates were observed in subgroups versus the overall population, indicating that ZEMY may be useful in symptom management in these patients. Generally, patients had a favorable opinion of ZEMY. The DD rate observed indicates the need for better user support in the future. Clinical trial information: NCT03558490.

Outcomes for Hyperthermia Combined with Concurrent Radiochemotherapy for Patients with Cervical Cancer

To evaluate the effect of hyperthermia combined with concurrent radiochemotherapy (RCT) and treatment-related toxicity in patients with cervical cancer (CC) stage IB-IV. This study was conducted between 2009 and 2013 in patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB-IV CC. The patients were randomly assigned into 2 treatment groups: RCT and RCT plus hyperthermia (RCHT). Five-year survival, treatment-related toxicity, and other prognostic factors were evaluated. Three hundred seventy-three patients completed treatment and were analyzed by per-protocol (PP) analysis. The 5-year overall survival (OS) in the RCHT group (81.9%) was better than that in RCT group (72.3%), and the log-rank test showed a statistically significant difference between the 2 groups (P = .040). Univariate and multivariate Cox regression analysis for 5-year OS showed a statistically significant difference (P = .043, P = .045, respectively). The 5-year local relapse-free survival in RCHT (86.8%) was also better than that in RCT (82.7%), but the difference was not significant. Acute or late toxicity was not significantly different between the 2 groups. Advanced clinical stage (FIGO) and larger tumor size showed higher risk of death and a relatively poor prognosis in univariate and multivariate analysis. The study confirmed that hyperthermia combined with RCT yielded a better 5-year OS in CC. Acute and late toxicity was similar between the RCT and RCHT groups. Clinical stage (FIGO) and tumor size were independent prognostic factors in CC.

Definitive radiotherapy in patients of synchronous esophageal and head and neck cancer-treatment outcome and toxicity

AimThe aim is to retrospectively evaluate the clinical outcomes and treatment related toxicities in patients of synchronous esophageal and head & neck cancer when treated with definitive radiotherapy with or without concurrent chemotherapy. BackgroundPatients of esophageal cancer with a synchronous second primary in head and neck region can be treated with definitive radiotherapy but the clinical outcome has been reported to be poor. Method and DesignThis is a single institutional retrospective study. Twenty-five patients fulfilling inclusion and exclusion criteria were evaluated. The survival was analysed using Kaplan–Meir method and their relations with various clinicopathologic parameters were compared. ResultsAfter a median follow-up time of 14 months, the 1 year and 2 year survival was 60% and 17% respectively. Significant improvement in overall survival was observed in patients with early staged esophageal cancer then locally advanced disease (P = 0.03). Patients with locally advanced head and neck cancer had poor survival than with early stage disease (P = 0.06). Those who received concurrent chemotherapy had better survival than those with radiotherapy alone. 40% patients developed grade III & IV dermatitis and 48% patients developed grade III oral mucositis. ConclusionChemoradiotherapy can safely be offered to patients with synchronous esophageal and head and neck cancer.

IBS14.02 Best Management of Early Stage NSCLC in ILD Patients

IBS14.02 Best Management of Early Stage NSCLC in ILD Patients

Individualized Adaptive Radiation Therapy Allows for Safe Treatment of Hepatocellular Carcinoma in Patients with Child-Pugh B Liver Disease

Liver stereotactic body radiation therapy (SBRT) is an effective treatment for hepatocellular carcinoma (HCC). However, previous reports suggest unacceptably high rates of treatment related toxicity in patients with Child Pugh B (CPB) liver disease. Our approach to limit toxicity in these patients has been to treat with an individualized adaptive approach, based on baseline and mid-treatment liver function. We hypothesized that this approach would maintain good local control while limiting toxicity in CPB patients receiving SBRT for HCC. Eighty patients with CPB liver disease and HCC were treated on prospective clinical trials of individualized adaptive radiation therapy at a single institution from 2006-2018. Patients underwent pre and mid-treatment liver function assessment using indocyanine green, a water soluble compound cleared exclusively by the liver, thereby providing a dynamic assessment of liver function. The mid-treatment assessment was typically performed one month after the delivery of the first 60% of the total intended dose, with the potential to receive 0-40% of the remaining dose after the 1 month break. Treatment related toxicity was defined as a ≥2 point rise in CP score from pre-treatment. Logistic regression models were used to assess predictors of toxicity and linear mixed models were used to assess longitudinal changes in CP score over time. Overall survival (OS) was assessed using Cox proportional hazard models. In total, 80 CPB patients with HCC were treated. Median follow-up was 13.1 months and median survival was 17.1 months. 37 patients were CPB-7, 28 CPB-8, and 15 CPB-9. Median tumor size was 2.6 cm. Median treatment dose was 36 Gy delivered in 3 fractions with a median mean liver dose (MLD) of 11.0 Gy. 2-year local control was 89.3%. Overall, 18 patients (22.5 %) had a ≥2 point rise in CP score within 6 months of SBRT. In a multivariate model assessing predictors of toxicity, baseline CP, tumor size, and MLD were not associated with toxicity (all p>0.35). In a longitudinal model assessing changes in CP score over 12 months post-SBRT, controlling for baseline CP and tumor size, increasing MLD was associated with an increased risk of eventual increase in CP score (p=0.04). In a multivariate model for OS controlling for tumor size and baseline CP score, increasing MLD was associated with decreased OS (HR: 1.04, 95% CI: 1.00-1.12, p=0.04). Tumor size and baseline CP score were not significantly associated with OS. Our individualized adaptive treatment approach allows for safe and effective treatment of patients with CPB liver disease. Our rates of treatment related toxicity in these high-risk patients is comparable to reported series in patients with Child-Pugh A liver dysfunction, and substantially less than those reported to date in CPB patients.

Evaluation of two nutritional scores' association with systemic treatment toxicity and survival in metastatic colorectal cancer: an AGEO prospective multicentre study

IntroductionThe Patient-Generated Subjective Global Assessment (PG-SGA) is currently the standard nutritional assessment tool for patients with cancer. In a retrospective assessment of a prospective cohort, we showed that the Nutritional Risk Index (NRI) seemed to be associated with treatment toxicity and survival in patients with metastatic colorectal cancer (mCRC). ObjectiveThe objective of this study was to compare these two nutritional tools (PG-SGA and NRI) on their correlation with chemotherapy-related toxicity and survival in non–pre-treated patients with mCRC. MethodsThis prospective multicentre observational study enrolled non–pre-treated patients with mCRC. PG-SGA and NRI were performed at the onset of first-line chemotherapy. Treatment-related toxicities were registered according to National Cancer Institute Common Toxicity Criteria Adverse Event version 4.0. Progression-free survival (PFS) and overall survival (OS) were calculated from the start of treatment. ResultsA total of 168 patients were included from eight French centres. Patients were considered malnourished in 41% of cases according to PG-SGA and 56% of cases according to the NRI. In multivariate analysis, malnutrition according to PG-SGA was significantly associated with chemotherapy-related grade ≥2 clinical toxicities (odds ratio: 3.7; 95% confidence interval [CI]: 1.7–8.4; p = 0.001) and OS (hazard ratio [HR]: 2.6; 95% CI: 1.3–5.3; p = 0.006), but not with PFS (HR: 1.5; 95% CI: 0.8–2.6; p = 0.2). Conversely, malnutrition according to the NRI was not significantly associated with these tolerance and efficacy parameters. ConclusionAlthough more complex to perform in daily oncology practice, the PG-SGA score appears to be the best nutritional assessment tool because of its strong association with clinically relevant oncological outcomes such as OS and treatment-related toxicities in patients with mCRC.

Real-world treatment patterns and adverse events in metastatic renal cell carcinoma from a large US claims database

BackgroundVascular endothelial growth factor (VEGF), tyrosine kinase (TK) and mechanistic target of rapamycin kinase (mTOR) inhibitors are common first-line (1 L) treatments for metastatic renal cell carcinoma (mRCC). Despite treatment availability, the 5-year survival rate in patients diagnosed at the metastatic stage is only ≈ 10%. To gain contemporary insights into RCC treatment trends that may inform clinical, scientific and payer considerations, treatment patterns and adverse events (AEs) associated with 1 L therapy were examined in a retrospective, longitudinal, population-based, observational study of patients with mRCC.MethodsUS administrative claims data (Truven Health MarketScan Commercial Databases) were used to assess trends in 1 L treatment initiation in mRCC (2006–2015) and characterize patterns of individual 1 L treatments, baseline characteristics, comorbidities and treatment-related AEs from 2011 through 2015. Outcomes were evaluated by drug class and route of administration.ResultsTen-year trend analysis (n = 4270) showed that TK/VEGF-directed therapy rapidly became more common than mTOR-directed therapy, and oral treatments were favored over intravenous (IV) treatments. Overall, 1992 eligible patients initiated 1 L treatment for mRCC from 2011 through 2015: 1752 (88%) received TK/VEGF-directed agents and 233 (12%) received mTOR-directed agents; 1674 (84%) received oral treatments, and 318 (16%) received IV treatments. The most common 1 L treatment was sunitinib (n = 849), followed by pazopanib (n = 631), temsirolimus (n = 157) and bevacizumab (n = 154). Patient characteristics and comorbidities, including age, diabetes and congestive heart failure, were independent predictors of 1 L mRCC treatment choice. The three most common potentially 1 L treatment–related AEs were nausea/vomiting (128.2 per 100 patient-years [PY]), hypertension (69 per 100 PY) and renal insufficiency (44.6 per 100 PY). A wide variety of agents were used as second-line (2 L) therapy. Substantial latency of onset was observed for several potentially treatment-related toxicities in patients treated with TK/VEGF- or mTOR-directed agents.ConclusionsIn the US, 1 L TK/VEGF inhibitor uptake in recent years appears largely in line with national approvals and guidelines, with varied 2 L agent use. Although retrospective evaluation of claims data cannot assess underlying causality, insights from these real-world RCC treatment and AE patterns will be useful in informing medical and payer decisions.

Adjuvant radiotherapy for Stage I seminoma: A Single-institutional experience.

There is no consensus regarding the management of Stage 1 seminomas following inguinal orchiectomy. In this study, we evaluated the treatment results and treatment-related toxicity for patients with Stage 1 seminomas treated with adjuvant radiotherapy (RT) at a single institution. Sixty-five patients who underwent adjuvant RT following orchiectomy for Stage 1 seminomas between January 1996 and December 2007 were retrospectively reviewed. The age, tumor location, histopathological type, stage, tumor size, RT field, and radiation dose were recorded for all patients. The patients' ages ranged from 17 to 61 years (median, 37 years). Sixty-three patients (97%) were diagnosed with classical seminoma and the remaining two patients (3%) had spermatocytic seminoma. After orchiectomy, 37 patients (57%) received para-aortic RT and 28 patients (43%) received dog-leg field RT. RT was applied with 1.8-2 Gy/day fractionation and the median RT dose was 26 Gy (range, 20-38). Follow-up ranged from 0.3 to 18 years (median, 9.5 years). Local control had been achieved in all patients and all of them were alive with no evidence of disease. Fifty-one patients (77%) had at least 5 years of follow-up and 27 patients (41%) had at least 10 years of follow-up. Overall survival at 10 years was 100%. Although retrospective in nature, this single-institutional study provides useful information about the outcomes and toxicities associated with adjuvant RT in patients with Stage 1 seminomas reporting excellent disease control and survival rates at the expense of acceptable toxicity.

Comment on: Managing morbidity and treatment-related toxicity in patients with ankylosing spondylitis.

Comment on: Managing morbidity and treatment-related toxicity in patients with ankylosing spondylitis.