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Opinion Statement: Chimeric antigen receptor (CAR) T-cell therapy has become the standard of care for children and young adults with relapsed and refractory B-cell acute lymphoblastic leukemia (B-ALL), and it is a highly promising therapy under investigation for adults with relapsed disease. Despite having potentially life-threatening toxicities, such as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, the benefits of CAR T-cell therapy far outweigh these risks, particularly as increased experience and improved supportive care measures are mitigating these toxicities. CAR T cells can result in complete remission for significant proportion of patients with relapsed and refractory B-ALL and permit them to proceed to potentially curative allogeneic hematopoietic stem cell transplantation (allo-HSCT). CAR T cells may also be curative by themselves. Herein lie the greatest challenges and questions for clinical investigators, specifically, how are CAR T cells best employed and how do we overcome mechanisms of resistance to them? The primary clinical question is the timing and even the necessity of allo-HSCT. Relative to resistance, we know that target antigen loss, specifically CD19, is a major contributor to resistance. However, current investigations of alternative targets, such CD22, and CAR T cells expressing dual targeting antigen receptors have demonstrated encouraging initial results and provide a high degree of optimism that the efficacy and the broader application of CAR T-cell therapy will gradually increase in B-ALL. That optimism is not as high and the challenges are increased for the application of CAR T cells in T-cell leukemias and acute myeloid leukemia due to the relative lack of suitable leukemia surface targets that are not also expressed on normal hematopoietic progenitors. Despite these significant challenges, considerable research is being conducted into the development of CAR T cells for these diseases utilizing unique technologies, which may be applicable to other diseases. [ABSTRACT FROM AUTHOR]

Background and purpose: Island blocking and dose leakage problems will lead to unnecessary irradiation to normal brain tissue (NBT) in hypofractionated stereotactic radiotherapy (HSRT) for multiple brain metastases (BM) with single-isocenter volumetric modulated arc therapy (VMAT). The present study aimed at investigating whether reducing the number of metastases irradiated by each arc beam could minimize these two problems. Materials and methods: A total of 32 non-small-cell lung cancer (NSCLC) patients with multiple BM received HSRT (24–36 Gy/3 fractions) with single-isocenter VMAT, where each arc beam only irradiated partial metastases (pm-VMAT), were enrolled in this retrospective study. Conventional single-isocenter VMAT plans, where each arc beam irradiated whole metastases (wm-VMAT), was regenerated and compared with pm-VMAT plans. Furthermore, the clinical efficacy and toxicities were evaluated. Results: Pm-VMAT achieved similar target coverage as that with wm-VMAT, with better dose fall-off (P < 0.001) and NBT sparing (P < 0.001). However, pm-VMAT resulted in more monitor units (MU) and longer beam-on time (P < 0.001). The intracranial objective response rate and disease control rate for all patients were 75% and 100%, respectively. The local control rates at 1 year and 2 year were 96.2% and 60.2%, respectively. The median progression-free survival and overall survival were 10.3 months (95% confidence interval [CI] 6.8–13.2) and 18.5 months (95% CI 15.9–20.1), respectively. All treatment-related adverse events were grade 1 or 2, and 3 lesions (2.31%) from 2 patients (6.25%) demonstrated radiation necrosis after HSRT. Conclusion: HSRT with pm-VMAT is effective and has limited toxicities for NSCLC patients with multiple BM. Pm-VMAT could provide better NBT sparing while maintaining target dose coverage. [ABSTRACT FROM AUTHOR]

Engineered T cell therapies such as chimeric antigen receptor (CAR) expressing T cells (CAR-T cells) have great potential to treat many human diseases; however, inflammatory toxicities associated with these therapies present safety risks and can greatly limit its widespread use. This article briefly reviews our current understanding of mechanisms for inflammatory toxicities during CAR T-cell therapy, current strategies for management and mitigation of these risks and highlights key areas of knowledge gap for future research. [ABSTRACT FROM AUTHOR]

Background: Hypofractionated radiotherapy (HypoRT) has been used to pursue an alternative treatment regimen for patients with non-small-cell lung cancer (NSCLC) who are not eligible for stereotactic ablative radiotherapy (SABR), surgery or concurrent chemoradiotherapy (CCRT) and has shown good local control and safety. We analyzed the feasibility of using volumetric-modulated arc radiotherapy (VMAT) with the simultaneous integrated boost (SIB) technique to achieve high local control with few treatment-related toxicities. Patients and Methods: A total of 55 patients with stage I-IV NSCLC who were not candidates for SABR, surgery or CCRT were included in the present study. All patients received a prescribed dose of 60 to 66 Gy in 15 fractions. Local progression-free survival (LPFS), PFS, overall survival (OS), and toxicities were retrospectively analyzed. Results: Thirty-three patients (60.0%) had stage IV or recurrent disease in this study. The median follow-up time was 8 months (interquartile range: 5.0-16.3 months). The 1-year and 2-year OS rates were 84.3% and 69.9%, and the 1-year and 2-year LPFS rates were 91.0% and 63.0%. The median OS (mOS) and median LPFS (mLPFS) were not reached, and median PFS (mPFS) was 15 months. Twenty-eight (51.9%) patients had disease progression at the time of analysis. Of these, 7 (13.0%), 7 (13.0%) and 21 (38.9%) had local recurrence, locoregional failure and distant metastasis, respectively. All cases of local recurrence were found within the SIB region. Four patients had grade 2-3 pneumonitis, and 8 patients had grade 2-3 esophagitis. Patients with grade 2-3 esophagitis had significantly higher maximum dose and dose to 5 cm3 volume to esophagus than those with grade 0-1 esophagitis. No grade 4 or higher toxicity was observed. Conclusion: The 60 to 66 Gy in 15 fractions RT regimen provides favorable local control and survival with well-tolerated toxicities. Hypofractionated VMAT+SIB is an alternative treatment option for patients with NSCLC who cannot tolerate standard definitive therapy. [ABSTRACT FROM AUTHOR]

• Split-course HFRT−CHT achieved satisfactory survival in postoperative LRR of NSCLC. • The regimen showed promising disease control and good tolerability. • Good PS, a single recurrence site and GTV<50cm3 tended to have better PFS and OS. • Early detection of LRR may improve the efficacy of HFRT−CHT. To explore the efficacy and toxicities of split-course hypo-fractionated radiotherapy with concurrent chemotherapy (HFRT−CHT) with intensity modulated radiotherapy (IMRT) technique in non-small cell lung cancer (NSCLC) patients with postoperative locoregional recurrence (LRR). NSCLC patients were eligible if confirmed as LRR disease without distant metastasis after complete resection. HFRT−CHT using IMRT technique was administered with 51 Gy in 17 fractions or 40 Gy in 10 fractions as the first course followed by a break. Patients with no disease progression and no persistent Grade ≥2 toxicities had the second course of 15 Gy in 5 fractions or 28 Gy in 7 fractions as a boost. The primary endpoint was progression-free survival (PFS). Fifty-eight patients were enrolled and analyzed. With a median follow-up of 23.9 months for all, the 2-year and 3-year PFS rate was 59.7 % and 46.4 %, the 2-year and 3-year OS rate was 72.5 % and 52.2 %, respectively, and a favorable objective response rate of 95.9 % was obtained after the whole courses protocol. Grade 3 acute pneumonitis and esophagitis occurred in 2 (3.4 %) and 7 (12.1 %) patients, and fatal pneumonitis was reported in one case (1.7 %). Exploratory subgroup analysis showed that performance status (PS) (PS 0 vs. 1: 2-year PFS, 88.1 % vs. 46.9 %, P = 0.001; 2-year OS, 100 % vs. 59.4 %, P < 0.001), recurrence site (single vs. multiple: 2-year PFS, 93.8 % vs. 47.4 %, P = 0.008; 2-year OS, 100 % vs. 63.0 %, P = 0.001), and gross tumor volume (GTV) (<50cm3 vs. ≥ 50cm3: 2-year PFS, 70.6 % vs. 46.2 %, P = 0.024; 2-year OS, 85.6 % vs. 57.4 %, P = 0.034) were significantly associated with PFS and OS. Split-course HFRT−CHT with IMRT technique achieved promising disease control and satisfactory survival with moderate toxicities in postoperative LRR of NSCLC. Good PS, a single recurrence site and GTV<50cm3 tended to have prolonged PFS and OS. Early detection of LRR may improve the efficacy of HFRT−CHT. [ABSTRACT FROM AUTHOR]

Xiao Li,1 Zhongguo Sui,1 Fanbo Jing,1 Wen Xu,1 Xiangpeng Li,1 Qie Guo,1 Shuhong Sun,1 Xiaolin Bi21Department of Clinical Pharmacy, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, People’s Republic of China; 2Department of Nutrition, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266003, People’s Republic of ChinaBackground: Whether monitoring of the methotrexate (MTX) concentrations after high-dose MTX (HD-MTX) infusion can predict toxicities is still controversial, especially when HD-MTX therapy is used in the treatment of children with acute lymphoblastic leukemia (ALL), which is different than the previous schedules. The relationship between patient characteristics and severe adverse events (AEs) has yet to be determined.Objective: To analyze the relationship between the MTX concentration and toxicities and to identify the risk predictors from patient characteristics for severe AEs during HD-MTX therapy in children with ALL.Methods: We conducted a retrospective study on children with ALL who were treated with 388 HD-MTX infusions. The chi-square test and univariate and logistic regression analyses were used to analyze the relationship between the MTX concentrations and toxicities and to identify predictors for severe AEs.Results: Febrile neutropenia (P=0.000) and vomiting (P=0.034) were more likely to occur if the infusion had an MTX level ≥1 μmol/L at 44 h, but other toxicities had no correlations with MTX concentration. Predictive factors for toxicities were as follows: higher risk stratification and higher values of albumin (ALB) for leucopenia, higher values of white blood cell count (WBC) for anemia, higher values of ALB and creatinine (Cr) for neutropenia, higher risk stratification and higher 44-h MTX concentration for febrile neutropenia, higher values of alanine transferase (ALT) for elevated ALT, higher values of ALT for elevated aspartate transferase (AST), and higher values of total bilirubin (TBil) for vomiting.Conclusion: Routine monitoring of 44-h MTX concentrations is essential to identify patients at high risk of developing febrile neutropenia and vomiting. This study may provide a reference for clinicians to distinguish patients with a relatively high risk of severe AEs based on certain characteristics before HD-MTX infusion.Keywords: high-dose methotrexate, methotrexate concentration, toxicities, patient characteristics, risk predictors, acute lymphoblastic leukemia

Abstract Concurrent chemotherapy (CCT) is used in locally advanced nasopharyngeal carcinoma (NPC) for improved local control, which could also be achieved by intensity‐modulated radiotherapy (IMRT). And for N2‐3 NPC, distant metastasis is the more important cause of death. This study aims to evaluate the value of CCT in N2‐3 NPC when neoadjuvant chemotherapy (NACT) of sufficient cycles is performed to eradicate distant metastasis. It enrolled 959 patients diagnosed with TxN2‐3M0 NPC from July 2011 to December 2015 and treated with NACT of 3‐4 cycles and IMRT. A propensity score matching (PSM) was made between patients treated with and without CCT (called the CCT and non‐CCT groups, respectively), using a series of clinical characteristics (age, gender, T stage, N stage, NACT regimen, and EBV DNA) as covariates. After PSM, the two groups of patients were compared on survivals and acute toxicities. The results indicated that no difference was seen in the overall, disease‐free, recurrence‐free or metastasis‐free survivals between the two groups. But compared with the CCT group, the non‐CCT group had a lower patient proportion of myelosuppression, nausea/vomiting, oral mucositis, cervical dermatitis, xerostomia, and grade 3/4 myelosuppression and oral mucositis (all P values were

Abstract The protective antioxidant activity of acetylcysteine (NAC) against toxicity due to cisplatin has been reported in experimental models; however, its efficacy in patients has not been elucidated. The aim of this study was to investigate the possible protective effect of NAC on cisplatin‐induced toxicity and the effect of NAC on clinical response and oxidative stress in patients treated for head and neck cancer. This was a randomized, double‐blind, placebo‐controlled trial conducted in patients receiving high‐dose cisplatin chemotherapy concomitant to radiotherapy. Patients were randomly assigned to groups and received: (a) 600 mg NAC syrup, orally once daily at night for 7 consecutive days or (b) placebo, administered similarly to NAC. Nephro‐, oto‐, hepato‐, myelo‐, and gastrointestinal toxicities, clinical responses, and plasma and cellular markers of oxidative stress were evaluated. Fifty‐seven patients were included (n = 28, NAC arm; and n = 29, placebo arm). A high prevalence of most types of toxicities was observed after cisplatin chemotherapy; however, the parameters were similar between the two groups. There was a predominance of partial response to treatment. In the cellular and plasmatic oxidative stress analyses, minor differences were observed. Overall, there was no statistically significant difference between the groups for all outcomes. These findings show that low‐dose oral NAC does not protect patients with head and neck cancer from cisplatin‐induced toxicities and oxidative stress. The antitumor efficacy of cisplatin was apparently not impaired by NAC.

Introduction: The chemotherapy schedules with cytotoxic dose or weekly regimes are still challenging, weighing the benefits versus toxicities. This prospective randomized study is an attempt to assess the efficacy of two schedules of cisplatin in management of locally advanced HNSCC. Objectives: The objectives of this study was to evaluate tolerance, tumour response and toxicities of concurrent chemoradiation with cisplatin in weekly and three weekly regimes. Methods: Locally advanced oropharyngeal squamous cell carcinoma patients fit for concurrent chemoradiation with cisplatin 40 mg/m2 (weekly) and 100 mg/m2 (3 weekly) were randomized to Arm A and B concurrently with radiotherapy of 70Gy/35frs/7 weeks. Statistical Analysis: Chi-square/ Fisher Exact test has been used to find the significance of study parameters on categorical scale between the groups. The statistical software SPSS 15.0 was used. Results: Between December 2010 and January 2013, 60 patients were enrolled. The median cycles of cisplatin in Arm-A was 5 and 2 in Arm-B. The complete response of 80.9% vs 75% and partial response of 14.3% vs 12.5% was observed in both arms respectively. There was no statistical difference in acute radiation and hematological toxicities between the two groups. With median follow up of 28 months, the 2 and 5 years overall survival was 55% and 58%; 41.6% and 32.3% in arms A and B respectively. Conclusion: In our study of locally advanced oropharyngeal carcinoma treated with radical radiotherapy comparing concurrent chemotherapy with cisplatin weekly vs 3 weekly had no significant difference in overall response, complete response and acute toxicities.

Phthalate esters (PAEs) are plasticizers associated with multiple toxicities; however, no strict regulations have been implemented to restrict their use in medical applications in Lebanon. Our study aimed at assessing the potential risks correlated with phthalate exposure from IV bags manufactured in Lebanon. GC–MS analysis showed that di-(2-ethylhexyl) phthalate (DEHP) is the predominant phthalate found in almost all samples tested with values ranging from 32.8 to 39.7% w/w of plastic. DEHP concentrations in the IV solutions reached up to 148 µg/L, as measured by SPME-GC–MS/MS, thus resulting in hazard quotients greater than 1, specifically in neonates. The toxicity of DEHP is mainly attributed to its metabolites, most importantly mono-(2-ethylhexyl) phthalate (MEHP). The IV bag solution with the highest content in DEHP was therefore used to extrapolate the amounts of urinary MEHP. The highest concentrations were found in neonates having the lowest body weight, which is concerning, knowing the adverse effects of MEHP in infants. Our study suggests that the use of IV bags manufactured in Lebanon could pose a significant risk in hospitalized patients, especially infants in neonatal care. Therefore, Lebanon, as well as other countries, should start imposing laws that restrict the use of phthalates in medical IV bags and substitute them with less toxic plasticizers.

Chimeric antigen receptor (CAR) T cell therapy has offered cancer patients a new alternative therapeutic choice in recent years. This novel type of therapy holds tremendous promise for the treatment of various hematologic malignancies including B-cell acute lymphoblastic leukemia (B-ALL) and lymphoma. However, CAR T cell therapy has experienced its ups and downs in terms of toxicities and efficacy shortcomings. Adverse events such as cytokine release syndrome (CRS), neurotoxicity, graft rejection, on-target off-tumor toxicities, and tumor relapse have tied the rescuing hands of CAR T cell therapies. Moreover, in the case of solid tumor treatment, CAR T cell therapies have not yielded encouraging results mainly due to challenges such as the formidable network of the tumor microenvironments (TME) that operates in a suppressive fashion resulting in CAR T cell dysfunction. In this review, we tend to shine a light on emerging strategies and solutions for addressing the mentioned barriers. These solutions might dramatically help shorten the gap between a successful clinical outcome and the hope for it.

To evaluate how women with epithelial ovarian cancer (EOC), dichotomized by BRCA status, tolerate intravenous (IV) or intraperitoneal (IP) chemotherapy given with veliparib and bevacizumab (bev) on a GOG phase I study (GOG 9923, NCT00989651). This is an unplanned, post hoc analysis of an IRB approved, multi-institutional, prospective study (GOG 9923). Clinical characteristics and toxicity data based on BRCA status were evaluated and descriptive statistics were used to summarize baseline patient characteristics and toxicities. The Kaplan Meier method was used to generate survival estimates. Four hundred twenty-four patients were evaluable. Patients were treated with IV carboplatin, paclitaxel, and bev every 21 days (regimen 1), weekly IV paclitaxel with carboplatin and bev (regimen 2) or IV paclitaxel and bev with IP cisplatin (regimen 3). Bev was continued as maintenance in all arms. Within each of these regimens, veliparib was given either twice daily for the entirety of each cycle (continuous) or on days −2 to 5 (intermittent). Ten percent of patients treated on regimen 1, 12% on regimen 2, and 19.8% on regimen 3 had BRCA- associated tumors. Patients with BRCA- associated tumors, when compared to wild type, experienced similar rates of anemia, febrile neutropenia (, abdominal pain, colonic perforation, nausea, vomiting, and peripheral sensory neuropathy. Median progression free survival (PFS) was not significantly different between BRCA- associated and wild type cancers (HR 0.96, CI 0.65–1.42), though this study's primary aim was not to evaluate outcomes. Germline BRCA mutations positively affect chemosensitivity in EOC, but whether differences in toxicities among BRCA- associated and BRCA wild type tumors existed was previously not reported. In this population with newly diagnosed ovarian cancer no differences in reported toxicity between the two groups was observed. • BRCA status does not affect hematologic AEs experienced by women receiving cytotoxic therapy with bevacizumab and veliparib. • Rates of non-hematologic and hematologic AEs were similar between all 3 regimens. • Rates of hematologic AEs were similar between continuous and intermittent veliparib dosing. • Median progression free survival was not significantly different between BRCA associated and wild type cancers. [ABSTRACT FROM AUTHOR]

Older 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. Chinese 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. A 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. The 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. [ABSTRACT FROM AUTHOR]

Chemotherapy drugs exert their effects by interfering with the cell cycle and the process of mitosis. Their therapeutic use stems from their ability to cause a greater proportion of cell kill in cancer cells as opposed to normal cells. In this article we discuss the clinical uses of chemotherapy, their mechanism of action, important toxicities and patterns of resistance. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor (CAR) T cell therapy has offered cancer patients a new alternative therapeutic choice in recent years. This novel type of therapy holds tremendous promise for the treatment of various hematologic malignancies including B-cell acute lymphoblastic leukemia (B-ALL) and lymphoma. However, CAR T cell therapy has experienced its ups and downs in terms of toxicities and efficacy shortcomings. Adverse events such as cytokine release syndrome (CRS), neurotoxicity, graft rejection, on-target off-tumor toxicities, and tumor relapse have tied the rescuing hands of CAR T cell therapies. Moreover, in the case of solid tumor treatment, CAR T cell therapies have not yielded encouraging results mainly due to challenges such as the formidable network of the tumor microenvironments (TME) that operates in a suppressive fashion resulting in CAR T cell dysfunction. In this review, we tend to shine a light on emerging strategies and solutions for addressing the mentioned barriers. These solutions might dramatically help shorten the gap between a successful clinical outcome and the hope for it. [ABSTRACT FROM AUTHOR]

Purpose of Review: Reporting of adverse events on hematology clinical trials is crucial to understanding the safety of standard treatments and novel agents. However, despite the importance of understanding toxicities, challenges in capturing and reporting accurate adverse event data exist. Recent Findings: Currently, adverse events are reported manually on most hematology clinical trials. Especially on phase III trials, the highest grade of each adverse event during a reporting period is typically reported. Despite the effort committed to AE reporting, studies have identified underreporting of adverse events on hematologic malignancy clinical trials, which raises concern about the true understanding of safety of treatment that clinicians have in order to guide patients about what to expect during therapy. In order to address these concerns, recent studies have piloted alternative methods for identification of adverse events. These methods include automated extraction of adverse event data from the electronic health record, implementation of trigger or alert tools into the medical record, and analytic tools to evaluate duration of adverse events rather than only the highest adverse event grade. Summary: Adverse event reporting is a crucial component of clinical trials. Novel tools for identifying and reporting adverse events provide opportunities for honing and refining methods of toxicity capture and improving understanding of toxicities patients experience while enrolled on clinical trials. [ABSTRACT FROM AUTHOR]

The rise and commercialization of perovskite solar cells (PSCs) is hindered by the toxicity of lead present in the perovskites used as the solar light absorber. To counter this problem, lead (Pb) can be fully (lead‐free) or partially (lead‐less) replaced by diverse elements. The former compounds suffer from poor efficiency and poor stability, whereas the later appear more promising. Herein, a survey of the methods reported in the literature to reduce Pb content in PSCs to fabricate "lead‐less" (also called "lead‐deficient") PSCs is offered. First, the comparison of Sn and Pb elements and the partial replacement of Pb by Sn are developed. Then, its substitution by either Ge, Sr, or other alkaline‐earth‐metals, transition metals, and elements from columns 12, 13, and 15 of the periodic table are detailed. The new families of perovskites based on the insertion of organic cations to replace lead and halogen units, namely the "lead‐deficient" and "hollow" halide perovskites are then presented and discussed. Finally, atypical ways to reduce the toxicity of PSCs are presented: perovskite layer thickness reduction via optimization of photon collection, integration of photonic structures, and usage of recycled lead. The current achievements and the outlook of those strategies are presented and discussed. [ABSTRACT FROM AUTHOR]

Introduction: Taxanes especially paclitaxel is a key chemotherapeutic agent in the management of non-metastatic breast cancer. Different schedules are utilized in management with weekly paclitaxel being one of the common regimes. The weekly regimen has a distinctive toxicity profile. Methods: This retrospective study was done to study the adverse effect profile of weekly paclitaxel used in the treatment of nonmetastatic breast cancer. Data were collected from case records of patients who received or were started on weekly paclitaxel single agent or in combination with trastuzumab between May and July 2019. Results: Eighty-eight patient case records were analyzed. The median age was 46.5 yrs (Range 30-67 yrs). The majority of patients received paclitaxel as an adjuvant (N=80, 91%). Sixty-one patients (69%) received single-agent paclitaxel while the remaining received it in combination with trastuzumab. Seventy-five percent (N=66) of patients did not have any modification of dosages in their regimen. Among those patients who required dose modification 19% (N=17) of patients required it from cycle 7 or beyond. Planned 12 cycles of weekly paclitaxel were completed in 81% (N=71) patients. The median duration for completion of 12 cycles from the start of chemotherapy was 80 days (Range 53-103). Major Grade 3/4 toxicities observed included peripheral neuropathy (12%) anemia (10%) and Neutropenia(4%). Conclusion: We observed a higher incidence of acute toxicities related to weekly paclitaxel though the majority of patients were able to complete their planned schedule of paclitaxel. [ABSTRACT FROM AUTHOR]

Responses to neoadjuvant chemoradiotherapy (nCRT) and therapy-related toxicities in rectal cancer vary among patients. To provide the individualized therapeutic option for each patient, predictive markers of therapeutic responses and toxicities are in critical need. We aimed to identify the association of gut microbiome with and its potential predictive value for therapeutic responses and toxicities. In the present study, we collected fecal microbiome samples from patients with rectal cancer at treatment initiation and just after nCRT. Taxonomic profiling via 16S ribosomal RNA gene sequencing was performed on all samples. Patients were classified as responders versus non-responders. Patients were grouped into no or mild diarrhea and severe diarrhea. STAMP and high-dimensional class comparisons via linear discriminant analysis of effect size (LEfSe) were used to compare the compositional differences between groups. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) was utilized to predict differences in metabolic function between groups. Ten patients were classified as responders and 12 patients were classified as non-responders. Fourteen patients experienced no or mild diarrhea and 8 patients experienced severe diarrhea. Several bacteria taxa with significantly different relative abundances before and after nCRT were identified. Similarly, several baseline bacteria taxa and predicted pathways with significantly different relative abundances between responders and non-responders or between patients no or mild diarrhea and severe diarrhea were identified. Specifically, Shuttleworthia was identified as enriched in responders and several bacteria taxa in the Clostridiales order etc. were identified as enriched in non-responders. Pathways including fatty acid metabolism were predicted to be enriched in responders. In addition, Bifidobacterium, Clostridia, and Bacteroides etc. were identified as enriched in patients with no or mild diarrhea. Pathways including primary bile acid biosynthesis were predicted to be enriched in patients with no or mild diarrhea. Together, the microbiota and pathway markers identified in this study may be utilized to predict the therapeutic responses and therapy-related toxicities of nCRT in patients with rectal cancer. More patient data is needed to verify the current findings and the results of metagenomic, metatranscriptomic, and metabolomic analyses will further mine key biomarkers at the compositional and functional level.

• Proton radiation offers unique advantage for thoracic neoplasms. • Protons can reduce toxicities with similar antitumor effect as conventional RT. • Protons permit safer dose-escalation and concomitant chemotherapy which may lead to improved disease control and survival. • Proton therapy may more safely allow for thoracic reirradiation with curative doses compared with photon therapy. Radiation therapy (RT) plays an important role in the curative treatment of a variety of thoracic malignancies. However, delivery of tumoricidal doses with conventional photon-based RT to thoracic tumors often presents unique challenges. Extraneous dose deposited along the entrance and exit paths of the photon beam increases the likelihood of significant acute and delayed toxicities in cardiac, pulmonary, and gastrointestinal structures. Furthermore, safe dose-escalation, delivery of concomitant systemic therapy, or reirradiation of a recurrent disease are frequently not feasible with photon RT. In contrast, protons have distinct physical properties that allow them to deposit a high irradiation dose in the target, while leaving a negligible exit dose in the adjacent organs at risk. Proton beam therapy (PBT), therefore, can reduce toxicities with similar antitumor effect or allow for dose escalation and enhanced antitumor effect with the same or even lower risk of adverse events, thus potentially improving the therapeutic ratio of the treatment. For thoracic malignancies, this favorable dose distribution can translate to decreases in treatment-related morbidities, provide more durable disease control, and potentially prolong survival. This review examines the evolving role of PBT in the treatment of thoracic malignancies and evaluates the data supporting its use. [ABSTRACT FROM AUTHOR]

Cisplatin is an effective anticancer drug used against a variety of cancers. The full therapeutic potential of cisplatin is often hampered due to concurrent development of various side effects in the hosts. Rutin, a naturally occurring bioflavonoid shows several pharmacological activities. It has been earlier reported by us that rutin and cisplatin in combination show better antitumor activity against murine ascites Dalton's lymphoma. As cisplatin is given to cancer-bearing hosts only, the present study was undertaken to explore the histoprotective effect of rutin against some toxicities induced by cisplatin in tumor-bearing mice. Cisplatin treatment caused severe damages in tissue architecture such as degenerated hepatocytes with nuclear condensation and sinusoidal dilatation in the liver, glomerular deterioration, infiltration of cells, and tubular congestion in the kidney, and vacuolization of Sertoli cells or dense granules in the cytoplasm and damaged seminiferous tubules in the testes. In the rutin plus cisplatin combination-treated mice, all the abnormal tissue architectural features were decreased. Further, as compared to cisplatin treatment, combination treatment did not show any significant elevation in the liver functional biomarkers (serum aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase) and renal functional biomarkers (serum urea and creatinine levels). The combination treatment reduced the sperm abnormalities also as compared to the cisplatin alone treatment. The in vitro hemolysis assay of red blood cells and scanning electron microscopy revealed that combination treatment lessened the cisplatin-induced hemolysis and abnormalities in RBCs. Thus, the present findings demonstrate that rutin has histoprotective ability against cisplatin-induced toxicities in tumor-bearing mice. [ABSTRACT FROM AUTHOR]

Background: Immunotherapy is a new and promising approach to treating pediatric cancers. These types of therapies have unique mechanisms of action for identifying and fighting cancer, as compared with traditional chemotherapy, and therefore are associated with different therapy-related adverse events (AEs). The purpose of this systematic review was to review available evidence to: (a) identify commonly reported AEs associated with immunotherapy agents frequently used in pediatric oncology and (b) generate recommendations for nursing practice. Method: A clinical question was developed and used to guide the systematic literature review. Five immunotherapy agents (dinutuximab, blinatumomab, rituximab, inotuzumab ozogamicin, brentuximab vedotin) were selected for inclusion secondary to their high relevance to pediatric oncology. A literature search was conducted to locate articles published between January 1, 2003 and October 31, 2018. Results: Seventeen articles met eligibility criteria for inclusion and were evaluated using the Grading of Recommendations Assessment, Development, and Evaluation criteria. The most commonly reported AEs for the selected immunotherapy agents were identified and summarized. Strong recommendations are made for nurses to become familiar with the unique AE profiles associated with individual immunotherapy agents. Agent-specific recommendations for nursing practice regarding AEs associated with dinutuximab and rituximab were generated. Conclusions: Immunotherapy is rapidly emerging as an effective therapy for pediatric cancers. Nurses need to be aware of the breadth of agent-specific, immunotherapy-related AEs to appropriately monitor and manage patients receiving these therapies. Additional work is needed to confidently profile immunotherapy-related AEs in pediatric oncology and to develop agent-specific educational materials for patients/families. [ABSTRACT FROM AUTHOR]

Background and Aims: Concurrent chemo-radiation in Head and neck cancer patients offers a significant improvement in local control and overall survival at the expense of added toxicities. In practice, different schedules of Cisplatin are used with concurrent chemo-radiation. This retrospective study aims to compare the toxicity profile of head and neck cancer patients treated with concurrent chemo-radiation using three weekly cisplatin and weekly cisplatin. Methods: This is a retrospective cohort study that included patients with Head and Neck Cancers treated with concurrent chemo-radiation with either of the two schedules of Cisplatin using 100 mg/m2 every three weeks or 40 mg/m2 every week. Conventional fields were used for radiation treatment. Treatment review charts were used to assess the toxicity of the treatment using RTOG toxicity grading criteria. χ2 test or fishers exact test were used to assess the difference between categorical variables. Continuous variables were compared with the two-sample t-test or Mann Whitney test when assumption could not be satisfied. Results: A total of 80 patients, of which 56 patients received the three weekly cisplatin while 24 patients had weekly cisplatin with concurrent chemo-radiation. Skin toxicity of Grade 3 at treatment completion was 5.4% in the three-weekly chemotherapy group, whereas it was 8.3% in the weekly chemotherapy group, which was statistically significant, (p=0.017). Mucous membrane toxicity was not statistically significant in any of the weeks of treatment. Pharyngeal toxicity reached statistical significance at the 4th week of treatment (p=0.015), but after treatment, no significant difference was seen between groups. Similarly, laryngeal toxicities between the groups were not statistically significant even though higher grade 3 toxicities started appearing from 3rd week. There is a statistically significant difference in terms of toxicities between the two treatment groups in body weight after treatment (p=0.01). When haematological toxicities were considered, hemoglobin toxicity of grade 2 occurred in 16.7% patients in the weekly chemotherapy group, while none at 3rd week which was statistically significant, (p=0.007) while none developed it in the three-weekly group. WBC toxicity showed a significant difference between the groups at the 5th and 6th week of treatment, p=0.001 and p=0.04 respectively with higher toxicity and percentages in the weekly chemotherapy group. Platelet toxicity of grade 2 developed in one patient in the weekly chemotherapy, but no statistically significant difference is seen in any of the weeks. The mean radiotherapy delay in days in the three weekly chemotherapy group was 0.36 day (SD 1.67) whereas in the weekly group was 1.33 days (SD 1.67), was not statistically significant. Treatment response was partial in 5.4% in the three weekly chemotherapy group and 4.2% in the weekly chemotherapy group; the difference noted is not statistically significant. Conclusions: There is heterogeneity in the severity of grade of toxicity within the three-weekly and weekly chemotherapy groups with concurrent chemoradiation. Weekly cisplatin appears more toxic as it is associated with higher grades of toxicities and chemotherapy interruptions. There is no evidence to show that weekly cisplatin is less toxic when compared to three weekly cisplatin in concurrent chemo-radiation for head and neck cancers. [ABSTRACT FROM AUTHOR]

Purpose: Stereotactic body radiation therapy (SBRT) has been established as a safe and effective treatment for prostate cancer. SBRT requires high accuracy to reduce treatment margins. Metal hip prostheses create artifacts that distort pelvic imaging and potentially decrease the accuracy of target/organ at risk (OAR) identification and radiation dose calculations. Data on the safety and efficacy of SBRT after hip replacement is limited. This single-institution study sought to evaluate the safety and local control following SBRT for prostate cancer in men with hip replacements., Methods: 23 patients treated with localized prostate cancer and a history of pre-treatment hip replacement, treated with SBRT from 2007 to 2017 at MedStar Georgetown University Hospital were included in this retrospective analysis. Treatment was administered with the CyberKnife ® (Accuray Incorporated, Sunnyvale, CA) at doses of 35 Gy or 36.25 Gy in 5 fractions. The targets and OARs were identified and contoured by a single experienced Radiation Oncologist (SPC). The adequacy of the CT and T2W MRI images for treatment planning was assessed with a three-point scale (good, adequate, or suboptimal). During treatment planning, care was taken to avoid treatment beams that directly traversed the hip prosthesis. Toxicities were recorded and scored using the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v.4.0). Local recurrence was confirmed by magnetic resonance imaging and/or prostate biopsy., Results: The median follow-up was seven years. The patients were elderly (median age = 71 years) with a high rate of comorbidities (Charlson Comorbidity Index > 2 in 25%). Four patients had bilateral hip replacements. The majority of patients were low to intermediate risk per the D'Amico classification. Around 13% received upfront ADT. In total, 13 patients were treated with 35 Gy, and 10 were treated with 36.25 Gy. The rates of late > Grade 3 GU toxicity and > Grade 2 GI toxicity were 8.6% and 4.3%, respectively. There were no Grade 4 or 5 toxicities. Six patients (26%) developed a local recurrence at a median time of 7.5 years. Of these six patients, four had unilateral hip replacements and two had bilateral. Three underwent salvage cryotherapy and three received salvage ADT., Conclusions:  In the general population, high-grade toxicities and local recurrences are uncommon following prostate SBRT. However, in this cohort of patients with prior hip replacements, prostate SBRT had higher than expected rates of late toxicity and local recurrence. In the opinion of the authors, such patients should be counseled regarding an elevated risk of late toxicity and local recurrence with prostate SBRT. With its ultrasound guidance, brachytherapy would have the advantage of circumventing the need for MRI/CT-based imaging and thus may represent a preferable radiation alternative in this patient population. If these patients are treated with SBRT, they should be monitored closely for local recurrence so early salvage can be performed. We hope that recent advances in metal artifact reduction techniques and dose-calculation algorithms will improve future outcomes., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Georgetown University Institutional Review Board issued approval 2009-510. Approval from the MedStar Georgetown University Institutional Review Board was obtained for retrospective review of prospectively collected data in our institutional database (IRB#: 2009-510). Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: This work was supported by the James and Theodore Pedas Family Foundation. Additionally, SP Collins serves as a clinical consultant to Accuray Inc. The Department of Radiation Medicine at Medstar Georgetown University Hospital recieves a grant from Accuray to support a research coordinator. The other authors declare they have no competing interests. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Shah et al.)

In the present study, we investigated the role of lipid composition of camptothecin (CPT)-loaded liposomes (CPT-Lips) to adjust their residence time, drug distribution, and therefore the toxicities and antitumor activity. The CPT was loaded into liposomes using a click drug loading method, which utilized liposomes preloaded with GSH and then exposed to CPT-maleimide. The method produced CPT-Lips with a high encapsulation efficiency (>95%) and sustained drug release. It is shown that the residence times of CPT-Lips in the body were highly dependent on lipid compositions with an order of non-PEGylated liposomes of unsaturated lipids < non-PEGylated liposomes of saturated lipids < PEGylated liposomes of saturated lipids. Interestingly, the fast clearance of CPT-Lips resulted in significantly decreased toxicities but did not cause a significant decrease in their in vivo antitumor activity. These results suggested that the lipid composition could effectively adjust the residence time of CPT-Lips in the body and further optimize their therapeutic index, which would guide the development of a liposomal formulation of CPT.

We report our initial real-world experience with 177 Lu-PSMA-617 radioligand therapy. Methods: We performed a retrospective review of patients treated with 177 Lu-PSMA-617. Pretreatment PSMA PET, laboratory findings, overall survival, a fall in prostate-specific antigen by 50% (PSA50), and toxicities were evaluated. Results: Ninety-nine patients were included. Sixty patients achieved a PSA50. Seven of 18 (39%) patients who did not meet the TheraP PSMA imaging criteria achieved a PSA50. Nineteen of 31 (61%) patients who did not meet the VISION laboratory criteria achieved a PSA50. Sixty-three patients had a delay or stoppage in therapy, which was due to a good response in 19 patients and progressive disease in 14 patients. Of 10 patients with a good response who restarted treatment, 9 subsequently achieved a PSA50 on retreatment. The most common toxicities were anemia (33%) and thrombocytopenia (21%). Conclusion: At our center, patients who did not meet the TheraP PSMA imaging criteria or the VISION laboratory criteria benefited from 177 Lu-PSMA-617 radioligand therapy., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Chimeric antigen receptor T cell therapy (CAR-T) has transformed the treatment landscape for adults with relapsed/refractory hematologic malignancies, but few studies have examined outcomes in older adults. We aimed to evaluate clinical outcomes and treatment toxicity in older adults receiving CAR-T for hematologic malignancies and to describe outcomes and toxicities in older adults age 75+ years compared to those age 65 to 74 years. We conducted a retrospective analysis of 141 adult patients age 65+ years (46.1% age 75+ years) who received commercial CAR-T at Massachusetts General Hospital between December 2017 and June 2023. We abstracted clinical outcomes from a review of the electronic health record, including (1) toxicity (ie, cytokine release syndrome [CRS] and immune effector cell-associated neurotoxicity syndrome [ICANS]); (2) health care utilization; (3) overall survival (OS); and (4) event-free survival (EFS). We analyzed the association of age (65 to 74 years versus 75+ years) with toxicity and health care utilization using the Mann-Whitney U test for continuous variables and the Fisher exact test for categorical variables. We examined the association of age with OS and EFS using multivariable Cox regression, controlling for covariates. The median patient age was 77 years (range, 75 to 91 years) in the 75+ year group and 69 years (ranges, 65 to 74 years) in the 65 to 74 year group. There were no statistically significant differences between the 75+ year group and the 65 to 74 year group in the rates of CRS (75.4% versus 84.2%; P = .21), grade 3+ CRS (1.5% versus 6.6%; P = .24), ICANS (38.5% versus 48.7%; P = .24), grade 3+ ICANS (16.9% versus 21.1%; P = .49), or infections (23.1% versus 29.0%; P = .45). There were no significant between-group differences in hospital readmissions within 30 days of CAR-T (10.8% versus 21.1%; P = .11), intensive care unit admissions within 30 days of CAR-T (7.7% versus 9.2%; P = 1.000), or median hospital length of stay (13 days versus 14 days; P = .29) among age groups. In a multivariable Cox regression analysis controlling for CAR-T product, Eastern Cooperative Oncology Group Performance Status, lactate dehydrogenase level, bridging therapy use, and history of deep venous thromboembolism, age 75+ years was not associated with OS (hazard ratio [HR], .95; P = .86) or EFS (HR, 1.28; P = .30). We identified favorable OS and toxicity outcomes across age categories in older adults receiving CAR-T for B cell non-Hodgkin lymphoma or multiple myeloma, underscoring that age alone is not a contraindication for CAR-T., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Introduction: This study compared outcomes in patients with inoperable esophageal squamous cell carcinoma (ESCC) undergoing curative-intent concurrent chemoradiotherapy (CCRT) with intensity-modulated radiotherapy (IMRT) versus intensity-modulated proton therapy (IMPT)., Methods: The study encompassed a retrospective cohort analysis of patients with inoperable ESCC who underwent curative-intent CCRT from January 1, 2015, to December 31, 2020, with data sourced from the Taiwan Cancer Registry Database. In this study, both IMRT and IMPT delivered a total equivalent effective dose of approximately 5040 cGy in 28 fractions, accompanied by platinum-based chemotherapy administered as per established protocols. Multivariate Cox regression analyses were performed to assess oncologic outcomes, and statistical analyses were conducted, including inverse probability of treatment-weighted and Fine and Gray method for competing risks., Results: The observed risks of ESCC-specific and all-cause mortality were lower in patients treated with IMPT compared with those treated with IMRT, with adjusted hazard ratios (aHRs) of 0.62 (95% confidence interval [CI]: 0.58-0.70) and 0.72 (95% CI: 0.66-0.80), respectively. IMPT also reduced grade 2 radiation-induced side effects, such as pneumonitis, fatigue, and major adverse cardiovascular events, with aHRs (95% CI) of 0.76 (0.66-0.82), 0.10 (0.07-0.14), and 0.70 (0.67-0.73), respectively. However, IMPT was associated with an increased risk of grade 2 radiation dermatitis, with aHR (95% CI) of 1.48 (1.36-1.60). No substantial differences were found in the incidence of radiation esophagitis between IMPT and IMRT when adjusting for covariates., Conclusion: IMPT seems to be associated with superiority over IMRT in managing patients with inoperable ESCC undergoing curative-intent CCRT, suggesting improved survival outcomes and reduced toxicity. These findings have significant implications for the treatment of ESCC, particularly when surgery is not an option., Competing Interests: Disclosure The authors declare no conflict of interest., (Copyright © 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Responses to neoadjuvant chemoradiotherapy (nCRT) and therapy-related toxicities in rectal cancer vary among patients. To provide the individualized therapeutic option for each patient, predictive markers of therapeutic responses and toxicities are in critical need. We aimed to identify the association of gut microbiome with and its potential predictive value for therapeutic responses and toxicities. In the present study, we collected fecal microbiome samples from patients with rectal cancer at treatment initiation and just after nCRT. Taxonomic profiling via 16S ribosomal RNA gene sequencing was performed on all samples. Patients were classified as responders versus non-responders. Patients were grouped into no or mild diarrhea and severe diarrhea. STAMP and high-dimensional class comparisons via linear discriminant analysis of effect size (LEfSe) were used to compare the compositional differences between groups. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) was utilized to predict differences in metabolic function between groups. Ten patients were classified as responders and 12 patients were classified as non-responders. Fourteen patients experienced no or mild diarrhea and 8 patients experienced severe diarrhea. Several bacteria taxa with significantly different relative abundances before and after nCRT were identified. Similarly, several baseline bacteria taxa and predicted pathways with significantly different relative abundances between responders and non-responders or between patients no or mild diarrhea and severe diarrhea were identified. Specifically, Shuttleworthia was identified as enriched in responders and several bacteria taxa in the Clostridiales order etc. were identified as enriched in non-responders. Pathways including fatty acid metabolism were predicted to be enriched in responders. In addition, Bifidobacterium , Clostridia , and Bacteroides etc. were identified as enriched in patients with no or mild diarrhea. Pathways including primary bile acid biosynthesis were predicted to be enriched in patients with no or mild diarrhea. Together, the microbiota and pathway markers identified in this study may be utilized to predict the therapeutic responses and therapy-related toxicities of nCRT in patients with rectal cancer. More patient data is needed to verify the current findings and the results of metagenomic, metatranscriptomic, and metabolomic analyses will further mine key biomarkers at the compositional and functional level. [ABSTRACT FROM AUTHOR]

Background: Reirradiation for locoregionally recurrent nasopharyngeal carcinoma (LR‐NPC) after high‐dose radiotherapy (RT) is challenging and usually is associated with poor survival and severe toxicities. Because of its physical and biological advantages over photon‐beam RT, carbon‐ion RT (CIRT) could be a potential treatment option for patients with LR‐NPC. Methods: Patients with LR‐NPC who underwent salvage therapy using CIRT at the Shanghai Proton and Heavy Ion Center between May 2015 and June 2019 were analyzed. CIRT doses were 50 to 69 gray equivalent (GyE) (2.0‐3.0 GyE per fraction). Overall survival (OS), local control, regional control, distant control, and acute and late toxicities were analyzed. Univariable and multivariable analyses of OS and local control were performed using the Cox regression model. Results: Among the 206 patients included, 139 patients (67.5%) had recurrent American Joint Committee on Cancer stage III or stage IV disease. With a median follow‐up of 22.8 months, the 2‐year OS, local control, regional control, and distant control rates were 83.7%, 58.0%, 87.3%, and 94.7%, respectively. Multivariable analysis revealed that older age (P =.017) was predictive of worse OS, whereas a larger tumor volume (P =.049) and a lower biological equivalent dose (P =.029) were associated with inferior local control. No patient developed an acute toxicity of ≥grade 3 during CIRT. Severe (≥grade 3) late toxicities included temporal lobe necrosis (0.97%), cranial neuropathy (0.49%), hearing loss (1.46%), xerostomia (0.49%), and mucosal necrosis (16.02%) (toxicities were graded using the Radiation Therapy Oncology Group and European Organization for Research and Treatment of Cancer criteria). Conclusions: Salvage treatment using CIRT is efficacious for patients with LR‐NPC and its toxicities are acceptable. CIRT may improve the survival and toxicity profiles substantially for patients with LR‐NPC compared with the reported results after photon‐based intensity‐modulated RT. Salvage carbon‐ion radiotherapy is effective and safe for patients with locoregionally recurrent nasopharyngeal carcinoma. It may substantially improve survival and toxicity profiles as compared with the results after photon beam–based IMRT. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate efficacy and safety of intensity-modulated radiotherapy (IMRT) in the management of esthesioneuroblastoma (ENB).Methods and Materials: A retrospectively analysis of 52 ENB patients treated with IMRT between 8/2008 and 8/2018 was performed. Thirteen of the 44 patients (29.5%) with newly diagnosed and 2 of the 8 patients with recurrent disease presented regional lymph node metastasis. The median dose of IMRT was 66 (range 52.5–75) Gy for all patients. Elective nodal irradiation (ENI) was provided to all excluding 6 patients in this cohort.Results: With a median follow-up time of 32.5 (6~121) months, the 3-year overall survival (OS), progression-free survival (PFS), local progression-free survival (LPFS), regional progression-free survival (RPFS), and distant metastasis-free survival (DMFS) rates for the entire cohort were 89.7, 69.5, 89.7, 95.1, and 85.4%, respectively. Multivariate analysis revealed that N-classification (N– vs. N+) at presentation was the only significant prognosticators for PFS. No significant prognosticator was identified for other survival outcome. No severe (i.e., grade 3 or 4) IMRT-induced acute toxicity was observed. Severe late toxicities were infrequent (11.5%), which included dysosmia (3.8%), hearing loss (3.8%), radiation brain injury (1.9%), and temporal lobe necrosis (1.9%). Moreover, late ocular toxicity secondary to IMRT was not observed.Conclusion: IMRT produced acceptable 3-year outcomes in terms of OS (89.7%), LPFS (89.7%), and RPFS (95.1%) rates without substantial late adverse effects. Further investigations for a more effective systemic strategy for distant disease control as well as a precision radiation technique for further improvement in local control are needed.

Multiple myeloma (MM) remains an incurable disease regardless of recent advances in the field. Therefore, a substantial unmet need exists to treat patients with relapsed/refractory myeloma. The use of novel agents such as daratumumab, elotuzumab, carfilzomib, or pomalidomide, among others, usually cannot completely eradicate myeloma cells. Although these new drugs have had a significant impact on the prognosis of MM patients, the vast majority ultimately become refractory or can no longer be treated due to toxicity of prior treatment, and thus succumb to the disease. Cellular therapies represent a novel approach with a unique mechanism of action against myeloma with the potential to defeat drug resistance and achieve long-term remissions. Genetic modification of cells to express a novel receptor with tumor antigen specificity is currently being explored in myeloma. Chimeric antigen receptor gene-modified T-cells (CAR T-cells) have shown to be the most promising approach so far. CAR T-cells have shown to induce durable complete remissions in other advanced hematologic malignancies like acute lymphocytic leukemia (ALL) and diffuse large B-cell lymphoma (DLBCL). With this background, significant efforts are underway to develop CAR-based therapies for MM. Currently, several antigen targets, including CD138, CD19, immunoglobulin kappa (Ig-Kappa) and B-cell maturation antigen (BCMA), are being used in clinical trials to treat myeloma patients. Some of these trials have shown promising results, especially in terms of response rates. However, the absence of a plateau is observed in most studies which correlates with the absence of durable remissions. Therefore, several potential limitations such as lack of effectiveness, off-tumor toxicities, and antigen loss or interference with soluble proteins could hamper the efficacy of CAR T-cells in myeloma. In this review, we will focus on clinical outcomes reported with CAR T-cells in myeloma, as well as on CAR T-cell limitations and how to overcome them with next generation of CAR T-cells.

The tumoricidal efficiency of human CAR-T cells is generally evaluated using immune-deficient mouse models; however, due to their immune-incompetency and the species-specific reactivity of a target antigen, these models are problematic to imitate CAR-T-induced adverse effects in the clinic. Epithelial cell adhesion molecule (EpCAM) is a tumor-associated antigen overtly presented on the cell surface of various carcinomas, making it an attractive target for CAR-T therapy. Here, we developed an anti-mouse EpCAM CAR to evaluate its safety and efficacy in immunocompetent mouse models. As previously reported for their human equivalents, murine EpCAM CAR-T cells exhibit promising anti-tumor efficacy in vitro and in vivo. However, after CAR-T infusion, various dose-depended toxicities including body weight loss, cytokine-release syndrome (CRS), and death were observed in both tumor-bearing and tumor-free mice. Pathological examination revealed unexpected and severe pulmonary immunopathology due to basal EpCAM expression in normal lung. While our study validates EpCAM CAR-T’s potent anti-tumor efficacy, it also reveals that EpCAM CAR-T cells used for the treatment of solid tumors may cause lethal toxicity and should, therefore, be evaluated in patients with caution.

Background: Immune checkpoint inhibitors (ICPIs) are gaining more popularity as a treatment for advanced cancers. However, immune-related adverse events (irAEs) limit their use. We aimed to assess the impact of irAEs and their treatment on clinical and survival outcomes. Materials and Methods: We retrospectively reviewed records of the patients who received ICPIs between 2011 and 2017. Descriptive analyses were employed to compare different groups. Kaplan–Meier curves and log-rank tests were used to estimate and compare overall survival durations. Results: Of 427 identified patients, 202 (47.3%) had one or more irAEs. Overall, the patients who developed irAEs had better overall survival than did patients with no-irAEs, regardless of immunosuppressant treatment (P < 0.01). Patients with mild irAEs who did not require immunosuppressive treatment had longer overall survival duration than did patients without irAEs (P < 0.01). Patients with three or more irAEs had longer median overall survival compared to patients with two or less irAEs (P = 0.01). Infliximab was associated with shorter duration of steroid use as compared to steroid treatment only (2 months [standard deviation (SD), 8] vs. 4 months [SD, 4]). Steroid treatment for >30 days was associated with higher rate of infections compared to shorter duration (P = 0.03). Conclusion: IrAEs are associated with favorable overall survival, regardless of immunosuppression treatment requirement. IrAEs involving multiple organs appeared to be beneficial for overall survival. Early infliximab use shortens the duration of steroid treatment and therefore balances better cancer outcomes with decreased risk of infection.

The inception of cancer treatment with chemotherapeutics began in the 1940s with nitrogen mustards that were initially employed as weapons in World War II. Since then, treatment options for different malignancies have evolved over the period of last seventy years. Until the late 1990s, all the chemotherapeutic agents were small molecule chemicals with a highly nonspecific and severe toxicity spectrum. With the landmark approval of rituximab in 1997, a new horizon has opened up for numerous therapeutic antibodies in solid and hematological cancers. Although this transition to large molecules improved the survival and quality of life of cancer patients, this has also coincided with the change in adverse effect patterns. Typically, the anticancer agents are fraught with multifarious adverse effects that negatively impact different organs of cancer patients, which ultimately aggravate their sufferings. In contrast to the small molecules, anticancer antibodies are more targeted toward cancer signaling pathways and exhibit fewer side effects than traditional small molecule chemotherapy treatments. Nevertheless, the interference with the immune system triggers serious inflammation- and infection-related adverse effects. The differences in drug disposition and interaction with human basal pathways contribute to this paradigm shift in adverse effect profile. It is critical that healthcare team members gain a thorough insight of the adverse effect differences between the agents discovered during the last twenty-five years and before. In this review, we summarized the general mechanisms and adverse effects of small and large molecule anticancer drugs that would further our understanding on the toxicity patterns of chemotherapeutic regimens.

Background: Many cancer patients use additional herbs or supplements in combination with their anti-cancer therapy. Green tea—active ingredient epigallocatechin-3-gallate (EGCG)—is one of the most commonly used dietary supplements among breast cancer patients. EGCG may alter the metabolism of tamoxifen. Therefore, the aim of this study was to investigate the influence of green tea supplements on the pharmacokinetics of endoxifen; the most relevant active metabolite of tamoxifen. Methods: In this single-center, randomized cross-over trial, effects of green tea capsules on endoxifen levels were evaluated. Patients treated with tamoxifen for at least 3 months were eligible for this study. After inclusion, patients were consecutively treated with tamoxifen monotherapy for 28 days and in combination with green tea supplements (1 g twice daily; containing 300 mg EGCG) for 14 days (or vice versa). Blood samples were collected on the last day of monotherapy or combination therapy. Area under the curve (AUC0–24h), maximum concentration (Cmax) and minimum concentration (Ctrough) were obtained from individual plasma concentration–time curves. Results: No difference was found in geometric mean endoxifen AUC0–24h in the period with green tea versus tamoxifen monotherapy (− 0.4%; 95% CI − 8.6 to 8.5%; p = 0.92). Furthermore, no differences in Cmax (− 2.8%; − 10.6 to 5.6%; p = 0.47) nor Ctrough (1.2%; − 7.3 to 10.5%; p = 0.77) were found. Moreover, no severe toxicity was reported during the whole study period. Conclusions: This study demonstrated the absence of a pharmacokinetic interaction between green tea supplements and tamoxifen. Therefore, the use of green tea by patients with tamoxifen does not have to be discouraged. [ABSTRACT FROM AUTHOR]

Chemo and targeted anticancer therapies present significant skin adverse reactions, which impair the patients' quality of life. Cutaneous toxicities lead to poor treatment adherence, drug cessation, and psychosocial distress. This review aims to summarize the current knowledge concerning the prevention and management of skin toxicity arising from these therapies. A systematic literature search on online databases was conducted. The categorization of the main preventive and treatment measures was performed according to the level of evidence. Management of skin adverse reactions of oncology treatments is very heterogeneous, which can be explained by the lack of sound evidence-based treatments. The most studied adverse effects are papulopustular eruption, xerosis, and hand–foot syndrome. Prevention of xerosis stands out as the strategy most supported by level II studies. With respect to treatment, the use of antibiotics in papulopustular eruption resulting from anti-epidermal growth factor receptor agents is the most evidence-based approach. In general, the number of studies published in the literature classified with a level II of evidence (52%) is similar to the ones classified as level IV (33%), making clear the need of more randomized controlled trials regarding the effectiveness of preventive and treatment measures of skin adverse reactions of chemo and targeted anticancer therapies. [ABSTRACT FROM AUTHOR]

• Survival of organ transplant recipients with lung cancer is reduced compared to historical norms in non-transplant patients. • Those treated with definitive therapy instage III and chemotherapy in stage IV NSCLC had survivals matching historic norms. • Adverse events from chemotherapy appear higher in transplant recipients and appear lessened with dose reductions. • Treated SCLC patients had survivals slightly lower than historic norms. Organ transplant recipients (OTR) have an increased risk of developing post-transplant malignancies with lung cancer being one of the most common. In this retrospective study, we investigated incidence, use of systemic therapy and outcomes from lung cancer in OTR. Materials and Methods: Patients diagnosed with lung cancer following a solid organ transplant at the University Health Network, Toronto, ON, CA, from January 1, 1980 to June 30, 2016 were included. Data for the study population, patient characteristics, treatments and outcomes were abstracted from solid OTR databases, our cancer registry and patient charts. Univariate Kaplan-Meier curves estimated median overall survival (OS) by histology, stage and systemic therapy. Amongst 7944 OTR (heart [N = 765], lung [n = 1668], liver [n = 2238], kidney [n = 3273]), 101 (1.3 %) developed lung cancer which were included in our analyses. Of these, 81 % were non-small cell lung cancer (NSCLC), 11 % small cell lung cancer (SCLC) and 8% neuroendocrine tumor (NET). Median OS (months) was 25 in those that presented with Stage I/II NSCLC (44 %); 25 for Stage III NSCLC (7%); 3 for Stage IV NCLC (31 %); 10 for Limited stage SCLC (6%); 2 for Extensive stage (ES) SCLC (5%). NSCLC patients that received palliative chemotherapy had an OS of 8 months; ES-SCLC patients that received chemotherapy had an OS of 6 months. Of all patients who received platinum doublets (n = 16), 10 (62.5 %) required dose reductions at some point. Five patients experienced febrile neutropenia (31 %); two (12 %) had other toxicities leading to discontinuation. Patients with stage I/II NSCLC and NET had poorer survival compared to historical norms in non-transplant patients. Patients who had stage III NSCLC or received palliative systemic therapy had survivals at or slightly below historic norms, although numbers were small. Chemotherapy can be administered in selected OTR patients though dose reductions and febrile neutropenia were common. [ABSTRACT FROM AUTHOR]

Antibodies to programmed death-1 receptor and its ligand (anti–PD-1/PD-L1) produce durable responses in many cancers. However, the long-term effects of anti–PD-1/PD-L1 blockade are not well defined. We identified the toxicities, health outcomes and health-related quality of life (HRQoL) amongst long-term survivors treated with anti–PD-1/PD-L1. We assessed 217 patients who received anti–PD-1/PD-L1 for melanoma, renal cell carcinoma or non–small-cell lung carcinoma between 2009 and 2017, with survival greater than two years after treatment. Patient and tumour characteristics, immune-related adverse events (irAEs), cardiometabolic parameters (glucose, blood pressure, body mass index [BMI]), body composition (using automated body composition analyser, computed tomography and Slice-o-matic software) and HRQoL outcomes were tracked. Among the included patients, most were men (70.3%) and at anti–PD-1/PD-L1 initiation had an average age of 61.0 years and median BMI of 28.5. Median overall survival was not reached; 33 (15.2%) died during the follow-up primarily from progressive cancer (n = 28). At the last follow-up, most patients' Eastern Cooperative Oncology Group performance status was 0 (38%) or 1 (41%). There was no difference in blood pressure, glucose or BMI from baseline to two years after treatment initiation. Body composition showed increased adiposity (p = 0.05), skeletal muscle mass (p = 0.03) and skeletal muscle gauge (p = 0.04). We observed chronic irAEs at the last follow-up including hypothyroidism (10.6%), arthritis (3.2%), adrenal insufficiency (3.2%) and neuropathy (2.8%). New diagnoses of type 2 diabetes (6.5%) and hypertension (6.0%) were observed, with uncertain relationship to anti–PD-1/PD-L1. Patient-reported outcomes compared favourably with cancer and general populations, although younger age (p = 0.003) and need for subsequent therapy (p = 0.03) were associated with worse HRQoL outcomes. Durable responses to anti–PD-1/PD-L1 therapy and favourable HRQoL outcomes are encouraging. Chronic events may be more common than previously thought although no clear chronic adverse cardiometabolic effects were observed. • Of patients surviving >24 months after antibodies to programmed death-1 receptor and its receptor therapy, most had durable benefit. • Health-related quality of life outcomes compared favourably to unselected cancer cohorts. • Chronic immune-related adverse events may be more common than previously thought. • No obvious long-term adverse cardiometabolic signals were noted. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate efficacy and safety of intensity-modulated radiotherapy (IMRT) in the management of esthesioneuroblastoma (ENB). Methods and Materials: A retrospectively analysis of 52 ENB patients treated with IMRT between 8/2008 and 8/2018 was performed. Thirteen of the 44 patients (29.5%) with newly diagnosed and 2 of the 8 patients with recurrent disease presented regional lymph node metastasis. The median dose of IMRT was 66 (range 52.5–75) Gy for all patients. Elective nodal irradiation (ENI) was provided to all excluding 6 patients in this cohort. Results: With a median follow-up time of 32.5 (6~121) months, the 3-year overall survival (OS), progression-free survival (PFS), local progression-free survival (LPFS), regional progression-free survival (RPFS), and distant metastasis-free survival (DMFS) rates for the entire cohort were 89.7, 69.5, 89.7, 95.1, and 85.4%, respectively. Multivariate analysis revealed that N-classification (N– vs. N+) at presentation was the only significant prognosticators for PFS. No significant prognosticator was identified for other survival outcome. No severe (i.e., grade 3 or 4) IMRT-induced acute toxicity was observed. Severe late toxicities were infrequent (11.5%), which included dysosmia (3.8%), hearing loss (3.8%), radiation brain injury (1.9%), and temporal lobe necrosis (1.9%). Moreover, late ocular toxicity secondary to IMRT was not observed. Conclusion: IMRT produced acceptable 3-year outcomes in terms of OS (89.7%), LPFS (89.7%), and RPFS (95.1%) rates without substantial late adverse effects. Further investigations for a more effective systemic strategy for distant disease control as well as a precision radiation technique for further improvement in local control are needed. [ABSTRACT FROM AUTHOR]

Background: Clinical trial reports often emphasize efficacy over harms, leading to misinterpretation of the risk‐to‐benefit ratio of new therapies. Clear and sufficiently detailed reporting of methods and results is especially important in the abstracts of trial reports, as readers often base their assessment of a trial on such information. In this study, we evaluated the quality of adverse event (AE) reporting and abstract quality in phase III randomized controlled trials (RCTs) of systemic therapies in breast and colorectal cancer. Methods: Medline, EMBASE, Cochrane Database of RCTs, and Cochrane Database of Systematic Reviews were searched from November 2005 to September 2018. Phase III RCTs evaluating systemic therapies in breast or colorectal cancer were included. Each article was independently reviewed by two investigators using a standardized data extraction form based on guidelines developed by the Consolidated Standards of Reporting Trials (CONSORT) group. Descriptive statistics, bivariate analysis, and multivariable linear regression were used to analyze data. All statistical tests were two‐sided. Results: Of 166 RCTs identified, 99.4% reported harms in the manuscript body, and 59.6% reported harms in the abstract. Reporting was restricted to severe harms in 15.6% of RCTs. Statistical comparison of AE rates went unreported in 59.0% of studies. Information regarding AEs leading to dose reductions, treatment discontinuations, or study withdrawals went unreported in 59.3%, 18.7%, and 86.8% of studies, respectively. Recently published RCTs (P =.009) and those sponsored at least partially by for‐profit companies (P =.003) had higher abstract quality scores. Conclusions: Breast and colorectal cancer phase III RCTs inadequately report CONSORT‐compliant AE data. Improved guideline adherence and abstract reporting is required to properly weigh benefits and harms of new oncologic therapies. Systematic Review Registration Number: CRD42019140673. [ABSTRACT FROM AUTHOR]

Background: Chimeric antigen receptor (CAR) T-cell therapy is an adoptive cellular immunotherapy that is being utilized more frequently due to its initial success in advanced-stage cancers. Unfortunately, CAR T-cell therapy is often associated with acute systemic toxicities, including cytokine release syndrome (CRS) and CAR T-cell-associated neurotoxicity (neurotoxicity).Objective: We created a review that addresses the potential common emergency department (ED) presentations associated with CAR T-cell therapy. We reviewed the relevant research and clinical guidelines to develop a guide tailored toward addressing the needs of the emergency medicine community to manage these complications. In addition, a case is presented and the evaluation and management of CRS and neurotoxicity are reviewed in detail.Discussion: Despite CAR T-cell designs showing promising results, the risk of acquiring an acute toxicity is high, with CRS and neurotoxicity reported most often. The systemic toxicities associated with these adverse events can lead to end-organ damage and compromise the patient acutely or jeopardize the continuation in treatment of their underlying malignancy. Depending on the severity of the toxicity, treatment typically starts with vigilant supportive care, but may include administration of tocilizumab and possibly high-dose corticosteroids if the toxicity is deemed of high severity.Conclusions: With the increasing administration of CAR T-cell therapy, emergency physicians will likely encounter more patients with associated adverse events, including CRS and neurotoxicity. It is increasingly important that emergency physicians are aware of these potential toxicities in order to rapidly diagnose and treat patients undergoing CAR T-cell therapy. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study is to understand the frequency of appropriate laboratory monitoring of oral chemotherapy at the Eastern Colorado Health Care System (ECHCS) compared to recommendations set forth in the 2012 Veterans Health Administration (VHA) Guidance on Dispensing and Monitoring of Oral Chemotherapy. Methods: This study is a retrospective chart review of patients who have received a subset of oral chemotherapy drugs at ECHCS. Patients 18 to 89 years of age with an active cancer diagnosis who initiated therapy at ECHCS between September 1, 2010 and August 31, 2014 were included in the study. Initial and subsequent prescription fill dates, appropriate labs as defined by VHA guidance and baseline and follow-up lab monitoring dates, and appropriate labs as defined by VHA guidance were collected for up to 12 cycles of chemotherapy per patient. Baseline labs were defined as within three months of the first prescription fill date, and follow-up labs were defined as within seven days of subsequent prescription fill dates. Results: Results are presented as complete, partial, or incomplete and as attempt or no attempt at monitoring according to the VHA guidance recommendations. There was 100% attempt at laboratory monitoring at baseline; however, there was a decline in attempt and complete follow-up monitoring overall as well as for drugs that require special monitoring. Conclusion: Based on recommendations from the 2012 VHA Guidance on Dispensing and Monitoring Oral Chemotherapy, data presented here demonstrate that ECHCS could benefit from improved lab monitoring in order to ensure safe and effective use of oral chemotherapies. These results provide a unique opportunity to consider the potential role of clinical pharmacists in monitoring and management of patients receiving oral chemotherapies as well as patient and provider education regarding the importance of appropriate lab monitoring. [ABSTRACT FROM AUTHOR]

• Sarcopenia is relevant for head and neck cancer patients treated with radiotherapy. • Sarcopenia is an independent adverse prognostic factor for survival outcomes. • For oropharyngeal cancer, survival is more defined by p16 status than by sarcopenia. • Sarcopenia is associated with late radiation-induced toxicities. Sarcopenia is emerging as an adverse prognostic factor for survival and complication risk in cancer patients. This study aims to determine the impact of sarcopenia on survival and late toxicity in a large cohort of head and neck squamous cell carcinoma (HNSCC) patients treated with definitive (chemo)radiotherapy ((C)RT). HNSCC patients treated with definitive (C)RT from January 2007 to June 2016 were included. Sarcopenia was assessed from radiation planning computed tomography (CT) scans using skeletal muscles at level C3. The impact of sarcopenia on overall survival (OS) and disease-free survival (DFS) was evaluated using the Kaplan–Meier method. Multivariable association models were developed to assess the impact of sarcopenia on late toxicity. The study population was composed of 750 HNSCC patients. Cut-off values for sarcopenia were set at SMI < 42.4 cm2/m2 (men) and <30.6 cm2/m2 (women) corresponding lowest gender specific quartile. Sarcopenic patients had significantly poorer survival rates, especially those with lower performance status and locally advanced disease. In oropharyngeal cancer patients, survival was more determined by p16 status than by sarcopenia. In multivariable analysis, sarcopenia was associated with worse OS (HR 0.72, p = 0.012) and DFS (HR 0.67, p = 0.001). In multivariable association models, sarcopenia was associated with physician-rated xerostomia six months after treatment (OR 1.65, p = 0.027) and physician-rated dysphagia six and twelve months after treatment (OR 2.02, p = 0.012 and 2.51, p = 0.003, respectively). Sarcopenia in HNSCC patients receiving definitive (C)RT is an independent prognostic factor for worse survival outcomes and is associated with physician-rated toxicity. [ABSTRACT FROM AUTHOR]

Purpose of Review: Ibrutinib is a first-in-class, highly potent Bruton tyrosine kinase inhibitor which has become standard of care for patients with chronic lymphocytic leukaemia and other lymphoproliferative disorders. It requires indefinite administration which places emphasis on toxicity and long-term tolerance. Recent Findings: Extensive use of ibrutinib in studies and clinical practice has better defined its full toxicity profile which has made its use more challenging than initially foreseen. In particular, dysrhythmias, bleeding, infections and constitutional symptoms have been reported and can result in dose reduction or discontinuation of ibrutinib. Summary: Herein, we review the common as well as rare but important toxicities and discuss approach and management on a practical level. We also highlight that patients should be regularly monitored for adverse events and proactively treated to minimise side effects and avoid disruption. [ABSTRACT FROM AUTHOR]

Immune-mediated toxicities are potentially fatal and can affect virtually any organ system. The prevalence of immune-mediated toxicity in patients being treated with immune checkpoint inhibitors (ICIs) is well described. However, the reasons for presentation and the prevalence of immune-mediated toxicity in acutely unwell patients being treated with ICIs is less well described. A prospective analysis of all emergency presentations in patients being treated with ICIs was performed at a specialist oncology hospital in England from 20th May 2018 to 19th May 2019. The primary outcome measure was whether the emergency presentation related to an immune-mediated toxicity. Secondary outcome measures were length of stay associated with immune-mediated toxicities and 7- and 30-day mortalities related to these presentations. During the study period, 300 patients on ICIs presented. The most common primary presenting complaints were dyspnoea 59 (19.7%), diarrhoea 47 (15.7%) and fever 37 (12.3%). Ninety-eight (32.7%) patients were diagnosed with an immune-mediated toxicity of which colitis 38 (38.8%), hepatitis 19 (19.4%) and pneumonitis 14 (14.3%) were the most common. The mean length of inpatient stay for those diagnosed with an immune-mediated presentation was 7.1 (0–45) days compared with 6.2 (0–44) days in those without. Seven patients died within 7 days of the emergency presentation, of whom 2 died from immune-mediated toxicity. One-third of cancer patients treated with ICIs admitted as an emergence had an immune-mediated toxicity and 2% died because of this. Acute care clinicians managing these patients need to be aware that immune-mediated toxicity is common in this patient population, but it can be challenging to differentiate these from other causes for emergency presentation. • One-third of emergency presentations in patients treated with checkpoint inhibitors are due to immune-mediated toxicity. • Median duration of admission for patients treated for an immune-mediated toxicity is 4 days. • Admitting under an acute oncology team with experience of IO toxicity is a model that allows optimisation of immediate management. • There may be a role for an immune-oncology advisory team to optimise outcomes for patients. • Management guidelines are empiric and more research is required, particularly at steroid sparing approaches. [ABSTRACT FROM AUTHOR]

Olaparib is the first poly(ADP-ribose) polymerase inhibitor approved as maintenance therapy of recurrent ovarian cancer (OC) patients with a BRCA mutation. To achieve the maximum clinical benefit, adherence to olaparib must be persistent. However, in clinical practice, this is challenged by the frequent suboptimal management of toxicities. In view of the expanding use of olaparib also in Italy, physicians must learn how to adequately and promptly manage drug toxicities not to unnecessarily interrupt or reduce the dose. The experts agreed that nausea,vomiting, anemia, and fatigue are the most frequent events experienced by OC patients on olaparib, and that these toxicities usually develop early during treatment, are mainly of grade 1-2 and transient and can be managed with simple non-pharmacological interventions. By sharing their real-world experiences, the panel prepared, for each toxicity, an algorithm organized by grade and besides the procedures indicated in the local label, included supportive care interventions based also on nutritional and lifestyle modifications and psycho-oncology consultation. Moreover, in view of the tablet entry into the Italian market, the full and reduced dosages of capsules and tablets were compared. This practical guidance is intended to be a tool to support especially less-experienced physicians in the management of these complex patients, with the aim to help preventing the worsening of patients' conditions and the unnecessary interruption/reduction of olaparib dosage, which may jeopardize treatment efficacy. [ABSTRACT FROM AUTHOR]

Background: The number of hemodialysis (HD) patients is increasing worldwide, and they are at a higher risk of cancer than the general population. Because HD patients are more likely to have inflammation, radiotherapy (RT)-induced adverse effects (AEs) are theoretically expected to be worse for HD patients. Since only a few reports have been published on this subject, we aimed to evaluate the tolerability of RT in HD patients. Methods: We retrospectively analyzed AEs related to RT for HD patients. Our study included patients from three institutions treated between January 2007 and July 2017. The patient eligibility criteria were (i) receipt of maintenance HD 2–3 times per week for end-stage renal disease prior to the start of RT and (ii) pathologically confirmed malignancies. The endpoints were acute and late non-hematologic AEs. Results: The study included 56 patients. The most common histology was head and neck cancer (23%), followed by lung cancer (14%) and prostate cancer (11%). The median radiation dose was 60 (range, 12–93.8) Gy at an equivalent dose in 2-Gy fractions (EQD2). The RT completion rate was 96%. Patients had a median follow-up period after RT of 9.1 (range 0.5–98.1) months. Grade 3 or worse acute and late AEs were noted in 6 (11%) and 3 (7%) patients, respectively. In the acute phase, 2 patients had grade 5 AEs, both of which were infections. Conclusion: Our results suggest that RT for HD patients is clinically tolerable. However, some patients can experience severe infections related to treatment. [ABSTRACT FROM AUTHOR]

Introduction: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been found to prolong survival in selected patients with peritoneal disease, but the extent of cytoreduction and chemoperfusion can result in systemic toxicities. We evaluate the incidence of perioperative hematological complications and its associated risk factors. Methods: Retrospective analysis of a prospectively collected database of CRS‐HIPEC cases between April 2001 and October 2016 was performed. Patients were stratified based on the clinicopathological characteristics, perioperative incidence, grade, and duration of leukopenia (white blood cells < 4000/mm3), neutropenia (absolute neutrophils < 2000/mm3), and thrombocytopenia (platelets < 140 000/mm3). Results: Two hundred and thirty‐five CRS‐HIPEC were performed in 220 patients with peritoneal metastasis of colorectal, ovarian, primary peritoneal, appendiceal, or mesothelioma origins. The incidences of leukopenia, neutropenia, and thrombocytopenia were 15.3%, 3.8%, and 37.9%, respectively. Median time to onset was 1 day (0‐16 days), 0 day (0‐2 days), and 1 day (1‐2 days), respectively, after operation. Median duration of leukopenia, neutropenia, and thrombocytopenia was 1 day (1‐3 days), 1 day (1‐2days), and 3 days (range 0‐16 days), respectively. Age > 60 (odds ratio [OR] 0.229 [95% CI: 0.105‐0.502], P <.001) and the use of prior chemotherapy (OR 2.46 [95% CI: 1.24, 4.83], P =.010) were independent risk factors for thrombocytopenia on multivariable logistic regression. Conclusion: Hematological toxicities are common after hyperthermic intraperitoneal chemotherapy with thrombocytopenia being most common. Patients with age > 60, and who have undergone chemotherapy, are at risk of these toxicities and should be closely monitored post CRS‐HIPEC. [ABSTRACT FROM AUTHOR]

Background: Although slow growing, head and neck paragangliomas (HNPG) can cause significant morbidity. We evaluated the efficacy of proton therapy in the management of HNPG. Methods: Retrospective review of an institutional proton therapy experience of treating patients between 1997 and 2016; 37 patients and 40 tumors were included. Results: Proton therapy was delivered to a median of 50.4 Gy(RBE) (range: 45‐68). Having a genetic/family predisposition for HNPG was associated with multifocal tumors (P =.02) and younger diagnosis age (P =.02). Twenty‐six (70%) patients had symptom improvement posttreatment, and 65% of treated tumors showed ≥20% volumetric shrinkage. The 5‐year recurrence‐free and overall survival rates were both 97%. Grade 2 to grade 3 toxicities (54%) included subjective hearing impairment (19%), middle ear inflammation (14%), and dry mouth (8%). There were no grade 4‐5 toxicities. Conclusions: Patients with HNPGs can be effectively and safely treated with proton therapy with excellent tumor control, successful volumetric tumor reduction, and symptomatic improvement. [ABSTRACT FROM AUTHOR]