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Purpose Despite the detrimental impact of chronic (chemotherapy-induced) peripheral neuropathy PN on patients’ lives, treatment options remain limited. We examined the association between mindfulness and chronic PN symptom severity and impairments in related patient-reported outcomes (PROs) among colorectal cancer (CRC) patients up to 2 years after diagnosis. Methods Newly diagnosed stage I–IV CRC patients from four Dutch hospitals were eligible for participation. Patients (N = 336) completed a questionnaire on mindfulness (MAAS) at 1 year after diagnosis, and questionnaires on sensory (SPN) and motor peripheral neuropathy (MPN) (EORTC QLQ-CIPN20), anxiety and depressive symptoms (HADS), sleep quality (PSQI), and fatigue (EORTC QLQ-C30) before initial treatment (baseline) and 1 and 2 years after diagnosis. Results At 1-year follow-up, 115 patients (34%) and 134 patients (40%), respectively, reported SPN or MPN symptoms. In multivariable regression analyses, higher mindfulness at 1-year follow-up was associated with less severe MPN and fewer anxiety and depressive symptoms, better sleep quality, and less fatigue. Of the patients with SPN or MPN at 1-year follow-up, symptoms had not returned to baseline level at 2-year follow-up in 59 (51%) and 72 (54%) patients, respectively. In this subgroup, higher mindfulness was associated with less severe SPN and fewer anxiety symptoms, depressive symptoms, and fatigue at 2-year follow-up. Conclusion Mindfulness was associated with less severe PN and better related PROs among CRC patients with chronic PN. More research is needed to examine the role of mindfulness in the transition from acute to chronic PN.

Recent discoveries in molecular diagnostics and drug treatments have improved the treatment of patients with advanced (inoperable) non-squamous non-small cell lung cancer (NSCLC) from solely platinum-based chemotherapy to more personalized treatment, including targeted therapies and immunotherapies. However, these improvements come at considerable costs, highlighting the need to assess their cost-effectiveness in order to optimize lung cancer care. Traditionally, costeffectiveness models for the evaluation of new lung cancer treatments were based on the findings of the randomized control trials (RCTs). However, the strict RCT inclusion criteria make RCT patients not representative of patients in the real-world. Patients in RCTs have a better prognosis than patients in a real-world setting. Therefore, in this study, we developed and validated a diagnosis-treatment decision model for patients with advanced (inoperable) non-squamous NSCLC based on real-world data in the Netherlands. The model is a patient-level microsimulation model implemented as discrete event simulation with five health events. Patients are simulated from diagnosis to death, including at most three treatment lines. The base-model (non-personalized strategy) was populated using real-world data of patients treated with platinum-based chemotherapy between 2008 and 2014 in one of six Dutch teaching hospitals. To simulate personalized care, molecular tumor characteristics were incorporated in the model based on the literature. The impact of novel targeted treatments and immunotherapies was included based on published RCTs. To validate the model, we compared survival under a personalized treatment strategy with observed real-world survival. This model can be used for health-care evaluation of personalized treatment for patients with advanced (inoperable) NSCLC in the Netherlands.

Introduction: Cancer is a burdensome disease whose treatment protocol can produce severe psychosocial and physical side effects. The main effects of antineoplastic treatment may affect the oral cavity, especially in children, compromising theirs and their family quality-of-life. Objective: To identify and describe side effects-related antineoplastic treatment and to assess its impact on the children’s and their families’ quality-of-life. Method: Qualitative and cross-sectional study, with the participation of 117 children, preschoolers, consulted at a referral hospital in the State of Paraíba, through the B-Ecohis questionnaire, dental clinical exams and medical records. The statistical treatment was based on descriptive analysis and Poisson Regression with robust variance in the Stepwise method (p

As a platinum-containing anticancer drug, cisplatin is the keystone for treating many malignancies. Nephrotoxicity is the main dose-limiting toxicity, and several hydration therapies and supplementary strategies are utilized to reduce cisplatin-induced kidney damage, so the discovery and development of effective and safe antitumor drugs are still on the path of human health. Herein, a new four-coordinated Pt complex [Pt(TSC)Cl] using N(4)-phenyl-2-formylpyridine thiosemicarbazone (HTSC) was synthesized and characterized by single-crystal X-ray diffraction, (HNMR)-H-1, FT-IR, LC/MS and CHN elemental analysis. The Pt(TSC)Cl complex revealed antiproliferative activity against A549, MCF-7 and Caco-2 cell lines with a low micromolar IC50 (200-1.75 mu M). Specifically, the Pt(TSC)Cl complex displayed more selectivity in Caco-2 cells (IC50 = 2.3 mu M) than cisplatin (IC50 = 107 mu M) after 48 h of treatment. Moreover, compared with cisplatin, a known nephrotoxic drug, the Pt(TSC)Cl complex exhibited lower nephrotoxicity against Hek293 normal cells. We also found that the Pt(TSC)Cl complex can effectively prevent cancer cell propagation in sub-G1 and S phases and induce apoptosis (more than 90%). Real time PCR and western analysis demonstrated that the expression pattern of apoptotic genes and proteins is according to the intrinsic apoptosis pathway through the Bax/Bcl-2-Casp9-Casp3/Casp7 axis. Collectively, our findings indicated that the Pt(TSC)Cl complex triggers apoptosis in Caco-2 cell lines, while low nephrotoxicity was shown and may be considered a useful anticancer drug candidate for colorectal cancers for further optimization and growth. The authors were financially supported by the National Institute for Medical Research Development (NIMAD) [Grant Number 964557] for the financial support of this research. The authors also highly appreciate Research Council University of Tabriz and University of Melbourne for X-ray crystallography.

BACKGROUND: Lorlatinib, a third-generation inhibitor of anaplastic lymphoma kinase (ALK), has antitumor activity in previously treated patients with ALK-positive non-small-cell lung cancer (NSCLC). The efficacy of lorlatinib, as compared with that of crizotinib, as first-line treatment for advanced ALK-positive NSCLC is unclear. METHODS: We conducted a global, randomized, phase 3 trial comparing lorlatinib with crizotinib in 296 patients with advanced ALK-positive NSCLC who had received no previous systemic treatment for metastatic disease. The primary end point was progression-free survival as assessed by blinded independent central review. Secondary end points included independently assessed objective response and intracranial response. An interim analysis of efficacy was planned after approximately 133 of 177 (75%) expected events of disease progression or death had occurred. RESULTS: The percentage of patients who were alive without disease progression at 12 months was 78% (95% confidence interval [CI], 70 to 84) in the lorlatinib group and 39% (95% CI, 30 to 48) in the crizotinib group (hazard ratio for disease progression or death, 0.28; 95% CI, 0.19 to 0.41; PCONCLUSIONS: In an interim analysis of results among patients with previously untreated advanced ALK-positive NSCLC, those who received lorlatinib had significantly longer progression-free survival and a higher frequency of intracranial response than those who received crizotinib. The incidence of grade 3 or 4 adverse events was higher with lorlatinib than with crizotinib because of the frequent occurrence of altered lipid levels. (Funded by Pfizer; CROWN ClinicalTrials.gov number, NCT03052608.).

PURPOSE: To explore the essential meaning of how sensory disturbances caused by Oxaliplatin influence self-understanding and freedom to live an everyday life among survivors after colorectal cancer.METHODS: Data was generated by means of a semi-structured individual interview with eight survivors after colorectal cancer who continued to experience chemotherapy-induced peripheral neuropathy at least one year after completing chemotherapy with Oxaliplatin. Data analysis was guided by existential phenomenology and descriptive life-world research.RESULTS: The essential meaning was structured by four constituents. 1) An unpleasant fluctuating sensation which is impossible to ignore, 2) Breaking through of noise and pain despite struggling to keep them at bay, 3) Continuously feeling ill despite being cured, and 4) Bodily constraints that impact self-understanding and limit enjoyment of life.CONCLUSION: The survivors used distraction to keep the sensory disturbances at bay but were forced to adapt to a new self-understanding as sufferers after chemotherapy despite being cured of their cancer disease. This way of being-in-the-world was understood by survivors, their families and healthcare professionals as a necessary price to pay to be alive. However, marked as sufferer after chemotherapy, the participants' everyday style of experience and life revealed as an ill health condition, which limited their ability to accomplish everyday activities as before and their freedom to realize their potential-the "I can".

BACKGROUND: Osimertinib is standard-of-care therapy for previously untreated epidermal growth factor receptor (EGFR) mutation-positive advanced non-small-cell lung cancer (NSCLC). The efficacy and safety of osimertinib as adjuvant therapy are unknown. METHODS: In this double-blind, phase 3 trial, we randomly assigned patients with completely resected EGFR mutation-positive NSCLC in a 1:1 ratio to receive either osimertinib (80 mg once daily) or placebo for 3 years. The primary end point was disease-free survival among patients with stage II to IIIA disease (according to investigator assessment). The secondary end points included disease-free survival in the overall population of patients with stage IB to IIIA disease, overall survival, and safety. RESULTS: A total of 682 patients underwent randomization (339 to the osimertinib group and 343 to the placebo group). At 24 months, 90% of the patients with stage II to IIIA disease in the osimertinib group (95% confidence interval [CI], 84 to 93) and 44% of thosein the placebo group (95% CI, 37 to 51) were alive and disease-free (overall hazard ratio for disease recurrence or death, 0.17; 99.06% CI, 0.11 to 0.26; P

Background About 30% of cancer survivors suffer from chemotherapy-induced peripheral neuropathy (CIPN) ≥6 months after completion of chemotherapy. This condition, for which treatment options are scarce, comes with limitations in daily life functioning and decreased quality of life. The current study examines the effectiveness of an online self-help intervention based on Acceptance and Commitment Therapy (ACT) in comparison to a waiting list condition (WLC) to deal with CIPN. In addition, it examines which factors moderate effects and to what extent the effects differ between guided and unguided ACT intervention. Methods A two-parallel, non-blinded randomized controlled trial (RCT) will be carried out. Adult cancer survivors who experience painful CIPN for at least 3 months and completed chemotherapy at least 6 months ago will be recruited (n=146). In the intervention condition, participants will follow an 8-week self-management course containing 6 modules regarding psychoeducation and ACT processes, including therapeutic email guidance. By means of text and experiential exercises, supplemented with illustrations, metaphors, and audio files, people will learn to carry out value-oriented activities in their daily life with pain. Participants will learn new ways of coping with pain, including reducing pain avoidance and increasing pain acceptance. Participants in the WLC will be invited to follow the intervention without therapeutic guidance 5 months after start. Pain interference is the primary outcome, while psychological distress, quality of life, CIPN symptom severity, pain intensity, psychological flexibility, mindfulness skills, values-based living, and pain catastrophizing will serve as secondary outcomes. All outcome measures will be evaluated at inclusion and baseline, early-intervention, mid-intervention, post-treatment, and 3- and 6-month post-treatment. Qualitative interviews will be conducted post-treatment regarding experiences, usage, usability, content fit, and satisfaction with the intervention. Discussion This study will provide valuable information on the effectiveness of an online self-help intervention based on ACT versus WLC for chronic painful CIPN patients. Trial registration ClinicalTrials.gov NCT05371158. Registered on May 12, 2022. Protocol version: version 1, 24-05-2022

© 2018 Sociedade Portuguesa de Cardiologia. Published by Elsevier España, S.L.U. This is an open access article under the CC-BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)., The use of tyrosine kinase inhibitors (TKIs) for the treatment of chronic myeloid leukemia has significantly altered the prognosis of this disease, enabling close to normal life expectancy. Despite their undeniable benefits, the use of TKIs is associated with an increased risk of side effects on the cardiovascular system, particularly of atherothrombotic events. It is therefore necessary to understand and prevent the adverse effects of these drugs, in order to enable antileukemic therapy to continue and to minimize patients’ toxic exposure. This multidisciplinary consensus document, developed through a collaboration between hematologists and cardiologists, aims to review the cardiovascular toxicity associated with various TKIs and to establish recommendations for the follow-up of these patients. Measures are also proposed for the assessment and reduction of cardiovascular risk in these patients and referral criteria, and relevant drug interactions are discussed., O uso dos inibidores da tirosina cínase (ITC) para o tratamento da leucemia mieloide crónica alterou significativamente o prognóstico dessa doença e permitiu uma esperança de vida praticamente normal. Apesar dos seus inegáveis benefícios, o uso dos ITC está associado a um aumento do risco de efeitos colaterais sobre o sistema cardiovascular, nomeadamente no risco de eventos aterotrombóticos. Torna-se por isso necessário conhecer e prevenir os efeitos adversos desses fármacos de modo a permitir a continuação da terapêutica antileucémica e minimizar a toxidade para os doentes. Este documento multidisciplinar, elaborado através de uma colaboração entre hematologistas e cardiologistas de vários serviços hospitalares portugueses, tem por objetivo rever a toxidade cardiovascular associada aos vários ITCs e estabelecer sugestões para o seguimento desses doentes. São ainda propostas medidas para a avaliação e redução do risco cardiovascular desses doentes, critérios de referenciação e discutidas interações medicamentosas relevantes.

Introduction: Several side effects can affect the skin and its attachments during cancer treatment of women with breast cancer, compromising the therapy. Objective: To identify the occurrence of dermatological changes during cancer treatment of women with breast cancer. Method: Quantitative approach, documentary and retrospective study, using secondary data obtained from 190 clinical records (n=190) from a private oncology service. Results: The participants had a mean age of 53 years (±11.2), with histopathological diagnosis of invasive ductal carcinoma (85.8%). All participants were exposed to chemotherapy, 65.3% to radical mastectomy and 34.2% to radiotherapy. The dermatological alterations identified, and the occurrences verified in the sample were alopecia (94.2%), hyperpigmentation (48.4%), pruritus (36.3%), erythema (6.8%), desquamation (25.8%) and nail alterations (77.9%). In all, 550 dermatological alterations were identified, resulting in an average of 2.9 (±1.3) changes per patient. Radiotherapy was associated with a higher occurrence of erythema (p

Introduction: The nutritional status of oncologic patients varies greatly throughout the disease, further to gastrointestinal tract related adverse effects that are common during chemotherapy treatment. Objective: Evaluate the nutritional status and the presence of gastrointestinal symptoms in oncologic patients undergoing chemotherapy. Method: Cross-sectional study with patients in treatment in the Chemotherapy Unit of the Hospital School of Pelotas Federal University (UFPel), RS, from April to July 2019. Sociodemographic data and questions related to the disease were obtained through a questionnaire. To assess the nutritional status and gastrointestinal symptoms the Patient-Generated Subjective Global Assessment was utilized. Data analysis was performed through descriptive analysis, and the association between categorical variables was verified by Pearson’s chi-square test (p

Key Points Question Is gestational age at initiation of chemotherapy during pregnancy associated with risk of congenital malformations? Findings In this cohort study including 755 pregnant women with cancer, the risk of major congenital malformations was elevated when first chemotherapy exposure was prior to 12 weeks of gestation, whereas the occurrence of major congenital malformations was similar to expected rates in the general population when chemotherapy was initiated after 12 weeks of gestation. Meaning The findings of this study could allow clinicians to better tailor chemotherapy during pregnancy and to inform patients on fetal risks of malformations., This cohort study assesses the association of gestational age at initiation of chemotherapy among pregnant women with cancer with congenital malformation rates among their offspring., Importance Chemotherapy during the first trimester of pregnancy should be avoided owing to the risk of congenital malformations. However, the precise gestational age at which chemotherapy can be initiated safely remains unclear. Objective To assess congenital malformation rates associated with gestational age at initiation of chemotherapy among pregnant women with cancer. Design, Setting, and Participants This multicenter cohort study evaluated all pregnant women who received chemotherapy between 1977 and 2019 registered in the International Network on Cancer, Infertility and Pregnancy (INCIP) database. Data were analyzed from February 15 to June 2, 2020. Exposures Cancer treatment with chemotherapy during pregnancy. Main Outcomes and Measures Analysis was focused on major and minor structural malformations in offspring, defined by EUROCAT, detected during pregnancy or at birth. Results A total of 755 women in the INCIP database who underwent cancer treatment with chemotherapy during pregnancy were included in analysis. The median (range) age at cancer diagnosis was 33 (14-48) years. Among offspring, the major congenital malformation rate was 3.6% (95% CI, 2.4%-5.2%), and the minor congenital malformation rate was 1.9% (95% CI, 1.0%-3.1%). Chemotherapy exposure prior to 12 weeks gestational age was associated with a high rate of major congenital malformations, at 21.7% (95% CI, 7.5%-43.7%; odds ratio, 9.24 [95% CI, 3.13-27.30]). When chemotherapy was initiated after gestational age 12 weeks, the frequency of major congenital malformations was 3.0% (95% CI, 1.9%-4.6%), which was similar to the expected rates in the general population. Minor malformations were comparable when exposure occurred before or after gestational age 12 weeks (4.3% [95% CI, 0.1%-21.9%] vs 1.8% [95% CI, 1.0-3.0]; odds ratio, 3.13 [95% CI, 0.39-25.28]). Of 29 women who received chemotherapy prior to 12 weeks gestation, 17 (58.6%) were not aware of pregnancy, and 6 (20.7%) experienced a miscarriage (3 women [10.3%]) or decided to terminate their pregnancy (3 women [10.3%]). Conclusions and Relevance This cohort study found that chemotherapy was associated with an increased risk of major congenital malformations only in the first 12 weeks of pregnancy. The risk of congenital malformations when chemotherapy was administered during the first trimester and the high number of incidental pregnancies during cancer treatment in the INCIP registry underscore the importance of contraceptive advice and pregnancy testing at the start of chemotherapeutic treatment in young women with cancer.

Supplemental digital content is available in the text., Introduction Given the growing population of colorectal cancer (CRC) survivors, identifying ways to enhance health-related quality of life (HRQoL) and alleviate complaints of fatigue and chemotherapy-induced peripheral neuropathy (CIPN) is essential. Purpose We aimed to assess longitudinal associations of sedentary behavior (SB) and moderate to vigorous physical activity (MVPA) independently, as well as their joint association, with HRQoL, fatigue, and CIPN in CRC survivors. Methods In a prospective cohort among stage I–stage III CRC survivors (n = 396), five repeated home visits from diagnosis up to 24 months posttreatment were executed. SB was measured using triaxial accelerometers, and MVPA, HRQoL, fatigue, and CIPN were measured by validated questionnaires. We applied confounder-adjusted linear mixed models to analyze longitudinal associations from 6 wk until 24 months posttreatment. Results Average time in prolonged SB (accumulated in bouts of duration ≥30 min) was 5.3 ± 2.7 h·d−1, and approximately 82% of survivors were classified as sufficiently active (≥150 min·wk−1 of MVPA) at 6 wk posttreatment. Decreases in SB and increases in MVPA were independently associated with better HRQoL and less fatigue over time. No associations were found for CIPN complaints. A synergistic interaction was observed between prolonged SB and MVPA in affecting functioning scales. Relative to CRC survivors with low prolonged SB and high MVPA, survivors with high prolonged SB and low MVPA reported a stronger decrease in physical functioning and role functioning over time than expected based on the independent associations of prolonged SB and MVPA. Conclusion Our longitudinal results show that less SB and more MVPA are beneficial for CRC survivors’ HRQoL and fatigue levels. Our findings regarding interaction underscore that joint recommendations to avoid prolonged sitting and accumulate MVPA are important.

Data on clinical use of ponatinib are limited. This prospective registry aimed to evaluate outcomes of ponatinib treatment in routine practice over 3 years (2016–2019) in Belgium (NCT03678454). Patients with chronic myeloid leukemia (CML) or Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) were treated with ponatinib per current label. Fifty patients (33 CML and 17 Ph+ ALL) were enrolled. Fifty-five percent of CML and 29% of Ph+ ALL patients had received ≥3 prior tyrosine kinase inhibitors (TKIs). Reasons for starting ponatinib were intolerance (40%), relapse or refractoriness (28%) to previous TKIs, progression (16%), or T315I mutation (16%). Median follow-up was 15 months for CML and 4.5 months for Ph+ ALL patients. Best response was a major molecular response in 58% of CML and 41% of Ph+ ALL patients. Of 20 patients who started ponatinib due to intolerance to previous TKIs, 9 (64%) CML and 4 (67%) Ph+ ALL achieved a major molecular response. Three-year estimates of overall survival were 85.3% and 85.6%, respectively, in CML and Ph+ ALL patients; estimated progression-free survival was 81.6% and 48.9%. Adverse reactions were reported in 34 patients (68%); rash (26%) and dry skin (10%) were most common. Reported cardiovascular adverse reactions included vascular stenosis (3), arterial hypertension (2), chest pain (1), palpitations (1), and vascular occlusion (1). This Belgian registry confirms results from the PACE clinical trial and supports routine ponatinib use in CML and Ph+ ALL patients who are resistant or intolerant to previous TKIs or with the T315I mutation. Supplementary Information The online version contains supplementary material available at 10.1007/s00277-021-04507-x.

Background Cancer patients are thought to have an increased risk of developing severe Coronavirus Disease 2019 (COVID-19) infection and of dying from the disease. In this work, predictive factors for COVID-19 severity and mortality in cancer patients were investigated. Patients and Methods In this large nationwide retro-prospective cohort study, we collected data on patients with solid tumours and COVID-19 diagnosed between March 1 and June 11, 2020. The primary endpoint was all-cause mortality and COVID-19 severity, defined as admission to an intensive care unit (ICU) and/or mechanical ventilation and/or death, was one of the secondary endpoints. Results From April 4 to June 11, 2020, 1289 patients were analysed. The most frequent cancers were digestive and thoracic. Altogether, 424 (33%) patients had a severe form of COVID-19 and 370 (29%) patients died. In multivariate analysis, independent factors associated with death were male sex (odds ratio 1.73, 95%CI: 1.18-2.52), ECOG PS ≥ 2 (OR 3.23, 95%CI: 2.27-4.61), updated Charlson comorbidity index (OR 1.08, 95%CI: 1.01-1.16) and admission to ICU (OR 3.62, 95%CI 2.14-6.11). The same factors, age along with corticosteroids before COVID-19 diagnosis, and thoracic primary tumour site were independently associated with COVID-19 severity. None of the anticancer treatments administered within the previous 3 months had any effect on mortality or COVID-19 severity, except cytotoxic chemotherapy in the subgroup of patients with detectable SARS-CoV-2 by RT-PCR, which was associated with a slight increase of the risk of death (OR 1.53; 95%CI: 1.00-2.34; p = 0.05). A total of 431 (39%) patients had their systemic anticancer treatment interrupted or stopped following diagnosis of COVID-19. Conclusions Mortality and COVID-19 severity in cancer patients are high and are associated with general characteristics of patients. We found no deleterious effects of recent anticancer treatments, except for cytotoxic chemotherapy in the RT-PCR-confirmed subgroup of patients. In almost 40% of patients, the systemic anticancer therapy was interrupted or stopped after COVID-19 diagnosis., Highlights • A total of 1289 patients with solid tumours and COVID-19 were analysed. • Mortality and COVID-19 severity were mainly driven by patient general characteristics. • Overall, we found no deleterious effects of recent anticancer treatments on mortality. . • Systemic anticancer treatment was interrupted or stopped in 39% of patients.

Background Data on the long-term effects of prenatal exposure to maternal cancer and its treatment on child development are scarce. Methods In a multicenter cohort study, the neurologic and cardiac outcomes of 6-year-old children born to women diagnosed with cancer during pregnancy were compared with the outcome of children born after an uncomplicated pregnancy. Assessment included clinical evaluation, comprehensive neuropsychological testing, electrocardiography and echocardiography. Results In total, 132 study children and 132 controls were included. In the study group, 97 children (73.5%) were prenatally exposed to chemotherapy (alone or in combination with other treatments), 14 (10.6%) to radiotherapy (alone or in combination), 1 (0.8%) to trastuzumab, 12 (9.1%) to surgery alone and 16 (12.1%) to no treatment. Although within normal ranges, statistically significant differences were found in mean verbal IQ and visuospatial long-term memory, with lower scores in the study versus control group (98.1, 95% confidence interval [CI]: 94.5–101.8, versus 104.4, 95% CI: 100.4–108.4, P = 0.001, Q, Highlights • Cancer treatment including chemotherapy is possible during pregnancy. • Children are at risk for lower verbal IQ and visuospatial long-term memory scores. • Other cognitive functions and cardiac outcomes were normal at the age of 6 years. • We documented ototoxicity in three children exposed to cisplatin. • Follow-up until adulthood is recommended.

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INTRODUCTION: Gastric cancer during pregnancy is extremely rare and data on optimal treatment and possible chemotherapeutic regimens are scarce. The aim of this study is to describe the obstetric and maternal outcome of women with gastric cancer during pregnancy and review the literature on antenatal chemotherapy for gastric cancer. MATERIAL AND METHODS: Treatment and outcome of patients registered in the International Network on Cancer, Infertility and Pregnancy database with gastric cancer diagnosed during pregnancy were analyzed. RESULTS: In total, 13 women with gastric cancer during pregnancy were registered between 2002 and 2018. Median gestational age at diagnosis was 22 weeks (range 6-30 weeks). Twelve women were diagnosed with advanced disease and died within 2 years after pregnancy, most within 6 months. In total, eight out of 10 live births ended in a preterm delivery because of preeclampsia, maternal deterioration, or therapy planning. Two out of six women who initiated chemotherapy during pregnancy delivered at term. Two neonates prenatally exposed to chemotherapy were growth restricted and one of them developed a systemic infection with brain abscess after preterm delivery for preeclampsia 2 weeks after chemotherapy. No malformations were reported. CONCLUSIONS: The prognosis of gastric cancer during pregnancy is poor, mainly due to advanced disease at diagnosis, emphasizing the need for early diagnosis. Antenatal chemotherapy can be considered to reach fetal maturity, taking possible complications such as growth restriction, preterm delivery, and hematopoietic suppression at birth into account. ispartof: ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA vol:99 issue:1 pages:79-88 ispartof: location:United States status: published

Introduction Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new drug delivery method used in patients with peritoneal cancer (PC) of primary or secondary origin. Intraperitoneal use of oxaliplatin raises concerns about toxicity, especially abdominal pain. The objective of this study was to assess the tolerance of PIPAC with oxaliplatin (PIPAC-Ox) in a large cohort of patients and to identify the risk factors for high grade toxicity, discontinuation of treatment and impaired survival. Material and methods This retrospective cohort study included all consecutive patients treated with PIPAC-Ox (92 mg/m2) in five centers specialized in the treatment of PC. The procedure was repeated every 6 weeks. Outcomes of interest were Common Terminology Criteria for Adverse Events (CTCAE), symptoms and survival (Kaplan-Meier). Univariate risk factors were included in a multinominal regression model to control for bias. Results Overall, 251 PIPAC-Ox treatments were performed in 101 patients (45 female) having unresectable PC of various origins: 66 colorectal, 15 gastric, 5 ovarian, 3 mesothelioma, 2 pseudomyxoma, 10 other malignancies (biliary, pancreatic, endocrine) respectively. The median PCI was 19 (IQR: 10–28). Postoperative abdominal pain was present in 23 patients. Out of the 9 patients with grade 3 abdominal pain, only 3 needed a change of PIPAC drug. CTCAE 4.0 toxicity grade 4 or higher was encountered in 16(15.9%) patients. The patients had a mean of 2.5 procedures/patient (SD = 1.5). 50 subjects presented with symptom improvement. Conclusions Oxaliplatin-based PIPAC appears to be a safe treatment that offers good symptom control and promising survival for patients with advanced peritoneal disease.

BACKGROUND: Awareness is growing that cancer can be treated during pregnancy, but the effect of this change on maternal and neonatal outcomes is unknown. The International Network on Cancer, Infertility and Pregnancy (INCIP) registers the incidence and maternal, obstetric, oncological, and neonatal outcomes of cancer occurring during pregnancy. We aimed to describe the oncological management and obstetric and neonatal outcomes of patients registered in INCIP and treated in the past 20 years, and assess associations between cancer type or treatment modality and obstetric and neonatal outcomes. METHODS: This descriptive cohort study included pregnant patients with cancer registered from all 37 centres (from 16 countries) participating in the INCIP registry. Oncological, obstetric, and neonatal outcome data of consecutive patients diagnosed with primary invasive cancer during pregnancy between Jan 1, 1996, and Nov 1, 2016, were retrospectively and prospectively collected. We analysed changes over time in categorical patient characteristics, outcomes, and treatment methods with log-binomial regression. We used multiple logistic regression to analyse preterm, prelabour rupture of membranes (PPROM) or preterm contractions, small for gestational age, and admission to the neonatal intensive care unit (NICU). The INCIP registry study is registered with ClinicalTrials.gov, number NCT00330447, and is ongoing. FINDINGS: 1170 patients were included in the analysis and 779 (67%) received treatment during pregnancy. Breast cancer was the most common malignant disease (462 [39%]). Every 5 years, the likelihood of receiving treatment during pregnancy increased (relative risk [RR] 1·10, 95% CI 1·05-1·15), mainly related to an increase of chemotherapeutic treatment (1·31, 1·20-1·43). Overall, 955 (88%) of 1089 singleton pregnancies ended in a livebirth, of which 430 (48%) of 887 pregnancies ended preterm. Each 5 years, we observed more livebirths (RR 1·04, 95% CI 1·01-1·06) and fewer iatrogenic preterm deliveries (0·91, 0·84-0·98). Our data suggest a relationship between platinum-based chemotherapy and small for gestational age (odds ratio [OR] 3·12, 95% CI 1·45-6·70), and between taxane chemotherapy and NICU admission (OR 2·37, 95% CI 1·31-4·28). NICU admission seemed to depend on cancer type, with gastrointestinal cancers having highest risk (OR 7·13, 95% CI 2·86-17·7) and thyroid cancers having lowest risk (0·14, 0·02-0·90) when compared with breast cancer. Unexpectedly, the data suggested that abdominal or cervical surgery was associated with a reduced likelihood of NICU admission (OR 0·30, 95% CI 0·17-0·55). Other associations between treatment or cancer type and outcomes were less clear. INTERPRETATION: Over the years, the proportion of patients with cancer during pregnancy who received antenatal treatment increased, especially treatment with chemotherapy. Our data indicate that babies exposed to antenatal chemotherapy might be more likely to develop complications, specifically small for gestational age and NICU admission, than babies not exposed. We therefore recommend involving hospitals with obstetric high-care units in the management of these patients. FUNDING: Research Foundation-Flanders, European Research Council, Charles University, Ministry of Health of the Czech Republic. ispartof: The Lancet Oncology vol:19 issue:3 pages:337-346 ispartof: location:England status: published

INTRODUCTION: A number of phase I immunotherapy trials for cancer patients incorporate the absolute lymphocyte count (ALC) as an inclusion criteria. This study aims to assess whether ALC is associated with a lack of response to anti-PD-1/PD-L1 in early clinical trials. METHODS: All consecutive patients treated with anti-PD-1/PD-L1 monotherapy in phase I trials in our institution between December 2011 and January 2014 were reviewed. Baseline ALC, neutrophil-to-lymphocyte ratio (NLR), Royal-Marsden Hospital (RMH) prognostic score, objective response rate (ORR) and disease control rate (DCR = SD + PR + CR, stable disease (SD), partial response (PR), complete response (CR)) defined by Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1 were retrieved. RESULTS: Out of a total of 167 patients, 48 (28.7%) and 8 patients (4.8%) had baseline ALCs of 1 G/l. When using 0.5 G/l as ALC threshold, we did not find any difference either in ORR or in DCR. In a multivariate Cox regression analysis, baseline ALC was not associated with overall survival, whereas the RMH and the number of previous lines of treatment remained independent prognostic factors. CONCLUSIONS: Baseline ALC was not associated with response to anti-PD-1/PD-L1 in cancer patients enrolled in phase I trials. Patients should not be excluded from early phase clinical trials testing immune checkpoints blockers because of ALC.

Alectinib, a highly selective inhibitor of anaplastic lymphoma kinase (ALK), has shown systemic and central nervous system (CNS) efficacy in the treatment of ALK-positive non-small-cell lung cancer (NSCLC). We investigated alectinib as compared with crizotinib in patients with previously untreated, advanced ALK-positive NSCLC, including those with asymptomatic CNS disease. In a randomized, open-label, phase 3 trial, we randomly assigned 303 patients with previously untreated, advanced ALK-positive NSCLC to receive either alectinib (600 mg twice daily) or crizotinib (250 mg twice daily). The primary end point was investigator-assessed progression-free survival. Secondary end points were independent review committee-assessed progression-free survival, time to CNS progression, objective response rate, and overall survival. During a median follow-up of 17.6 months (crizotinib) and 18.6 months (alectinib), an event of disease progression or death occurred in 62 of 152 patients (41%) in the alectinib group and 102 of 151 patients (68%) in the crizotinib group. The rate of investigator-assessed progression-free survival was significantly higher with alectinib than with crizotinib (12-month event-free survival rate, 68.4% [95% confidence interval (CI), 61.0 to 75.9] with alectinib vs. 48.7% [95% CI, 40.4 to 56.9] with crizotinib; hazard ratio for disease progression or death, 0.47 [95% CI, 0.34 to 0.65]; P

Resumo: Introdução e objetivos: A avaliação seriada da fração de ejeção ventricular esquerda (FEVE) é o padrão de referência na vigilância da cardiotoxicidade induzida por quimioterapia (CIT). A avaliação da deformação longitudinal com técnicas de speckle tracking permite uma avaliação mais detalhada da contractilidade miocárdica. O objetivo deste estudo foi avaliar a relação entre a deformação longitudinal global (GLS) e regional e a incidência de CIT. Métodos: Foram incluídos 158 pacientes num estudo prospetivo observacional de doentes com neoplasia da mama submetidos a quimioterapia com antraciclinas, com ou sem terapêutica adjuvante com trastuzumab. Foi efetuada uma monitorização ecocardiográfica seriada de parâmetros de função sistólica e diastólica, incluindo a avaliação da deformação miocárdica longitudinal bidimensional. A incidência de CIT foi definida como uma diminuição da FEVE para valor

SummaryBackground AZD4547 is a potent, oral, highly selective fibroblast growth factor receptor (FGFR) inhibitor in clinical development for treating tumours with a range of FGFR aberrations, including FGFR mutations, amplifications and fusions. Methods This open-label, Phase I, multicentre study (NCT01213160) evaluated the safety, pharmacokinetics, and preliminary antitumour efficacy (RECIST v1.1) of AZD4547 monotherapy in Japanese patients with advanced solid tumours. Part A was a dose-escalation part; Part B was a dose-expansion part in patients with FGFR-amplified tumours, confirmed by fluorescence in situ hybridization. Results Thirty patients enrolled in Part A (dose range: 40 mg twice daily [bid] to 120 mg bid; 160 mg once daily [qd]), four in Part B (80 mg bid). No dose-limiting toxicities were observed and maximum tolerated dose was not determined. Most common adverse events (AEs; any grade) were: dysgeusia (50% of patients); stomatitis (41%); diarrhoea (38%); hyperphosphataemia (38%); dry mouth (35%). Common grade ≥3 AEs were nausea (12% of patients) and neutropenia (9%). No complete or partial responses were observed: 21/30 patients had stable disease ≥4 weeks in Part A, and 1/4 patients had stable disease ≥10 weeks in Part B. Following single and multiple dosing, absorption rate appeared moderate; peak plasma concentrations generally occurred 3–4 h post-dose, then declined biphasically with terminal half-life ~30 h. Steady state was reached by day 8. Compared with single dosing, plasma concentrations were, on average, 2.4- and 3.3- to 5.4-fold higher after qd and bid dosing, respectively. Conclusions AZD4547 was well tolerated in Japanese patients, with best response of stable disease ≥4 weeks.

Background Because of the potential mutagenic effects of chemo- and radiotherapy, there is concern regarding increased risk of congenital malformations (CMs) among children of fathers with cancer. Previous register studies indicate increased CM risk among children conceived after paternal cancer but lack data on oncological treatment. Increased CM risk was recently reported in children born before paternal cancer. This study aims to investigate whether anti-neoplastic treatment for testicular germ-cell cancer (TGCC) implies additional CM risk. Methods and findings In this nationwide register study, all singletons born in Sweden 1994–2014 (n = 2,027,997) were included. Paternal TGCC diagnoses (n = 2,380), anti-neoplastic treatment, and offspring CMs were gathered from the Swedish Norwegian Testicular Cancer Group (SWENOTECA) and the Swedish Medical Birth Register. Children were grouped based on +/- paternal TGCC; treatment regimen: surveillance (n = 1,340), chemotherapy (n = 2,533), or radiotherapy (n = 360); and according to time of conception: pre- (n = 2,770) or post-treatment (n = 1,437). Odds ratios (ORs) for CMs were calculated using logistic regression with adjustment for parental ages, maternal body mass index (BMI), and maternal smoking. Children conceived before a specific treatment acted as reference for children conceived after the same treatment. Among children fathered by men with TGCC (n = 4,207), 184 had a CM. The risk of malformations was higher among children of fathers with TGCC compared with children fathered by men without TGCC (OR 1.28, 95% confidence interval [CI] 1.19–1.38, p = 0.001, 4.4% versus 3.5%). However, no additional risk increase was associated with oncological treatment when comparing post-treatment–to pretreatment-conceived children (chemotherapy, OR = 0.82, 95% CI 0.54–1.25, p = 0.37, 4.1% versus 4.6%; radiotherapy, OR = 1.01, 95% CI 0.25–4.12, p = 0.98, 3.2% versus 3.0%). Study limitations include lack of data on use of cryopreserved or donor sperm and on seminoma patients for the period 1995–2000—both tending to decrease the difference between the groups with TGCC and without TGCC. Furthermore, the power of analyses on chemotherapy intensity and radiotherapy was limited. Conclusions No additional increased risk of CMs was observed in children of men with TGCC treated with radio- or chemotherapy. However, paternal TGCC per se was associated with modestly increased risk for offspring malformations. Clinically, this information can reassure concerned patients., Yahia Al-Jebari and colleagues reveal no increased risk of congenital malformations in children of men treated for testicular germ cell cancer., Author summary Why was this study done? Chemotherapy and radiotherapy have both been shown to cause mutations and genetic damage in animal studies, leading to fears that men being treated with these therapies might be more prone to have children with genetic diseases and birth defects. This study investigates whether receiving treatment for testicular cancer, being the most common cancer among young men (in child-having ages), leads to a higher risk of fathering a child with a birth defect. What did the researchers do and find? By accessing data from Swedish national registries, we gathered data on more than 2 million newborns and their fathers. Among them, 2,380 fathers had testicular cancer and they had, in total, 4,207 children. When comparing the children conceived after the father received cancer treatment to the children born before treatment, we could not find any evidence showing that chemotherapy or radiotherapy leads to an increased risk of birth defects. We did see that there was, irrespectively of cancer treatment, a small risk increase associated with the fathers’ testicular cancer itself, meaning that men with testicular cancer have an approximately 30% higher relative risk of having a child with a birth defect (an increase from 3.5% to 4.4%). What do these findings mean? There was no risk increase due to cancer therapies. The risk increase detected was associated with testicular cancer. However, this risk increase is very small and relates to rare conditions. Because the risk increase is small, we therefore do not consider this cause for concern and wish this reassuring information to be passed on to patients.

Purpose The present study summarizes the first experience with 177Lu-PSMA-617 (177Lu-PSMA) treatment in metastatic castration-resistant prostate cancer (PCa) in our institution. Methods This was an analysis of the first 30 consecutive patients who underwent 177Lu-PSMA therapy. Biochemical response was defined as prostate-specific antigen decrease of 50% or greater. Clinical toxicity was based on standardized physician's report, and biochemical and hematological toxicity was graded according to the Common Toxicity Criteria for Adverse Events (CTCAE) criteria. Clinical response was objectified in terms of severity of pain and usage of analgesics after separate treatment cycles. Results Thirty patients with advanced PCa received therapy cycles with 6 GBq 177Lu-PSMA (median, 4; range, 1-6). After the first cycle, usage of analgesics decreased in 45% of the patients. During treatment, maximum prostate-specific antigen decrease was 50% or greater and 90% or greater in 57% and 24% of the patients, respectively. Despite CTCAE grades III and IV anemia occurring in 2 patients (7%), all other newly originated biochemical toxicity was limited to maximum CTCAE grades I and II. Grade II xerostomia occurred in 17% of the patients. During a median follow-up length of 13.7 months (range, 9.8-32.3 months), median overall survival from start of the first therapy cycle was 11.3 months (range, 1.4-32.3 months). Conclusions These results confirm the favorable safety and efficacy profile of 177Lu-PSMA, even up to 6 treatment cycles. Therefore, 177Lu-PSMA seems a promising therapeutic strategy for metastatic castration-resistant PCa patients. However, randomized controlled trials are warranted to obtain robust data.

SUMMARY INTRODUCTION: Drug interaction is an important cause of global morbidity. It is of particular importance in cancer patients since they are often in use of polypharmacy, related to interactions between the drugs and the chemotherapeutics used. OBJECTIVE: To evaluate the drug interaction between chemotherapy and other drugs in cancer patients. METHODS: a cross-sectional study carried out in the outpatient oncology department of a public tertiary hospital. Two hundred thirty-five patients were included, and the drugs they were using were identified. Using the MedScape and Epocrates database, we evaluated the interactions between medications and chemotherapy by defining their frequency and dividing their severity from interaction into mild, close monitoring necessity and severe. RESULTS: 161 patients had some drug interaction. We identified 9 types of mild interactions, 23 types of interactions with close monitoring necessity, and 2 types of serious interactions. The most frequent interactions were between fluorouracil and leucovorin (32 cases) and cyclophosphamide and doxorubicin (19 cases). Serious interactions were between aspirin and pemetrexed; and leucovorin and Bactrim. CONCLUSION: In the present study, drug interactions were frequent, including serious interactions with a potential increase in morbidity and mortality. Thus, it is necessary for oncologists to draw up a therapeutic plan considering potential interactions between prescribed chemotherapy and current medications in use by patients. RESUMO INTRODUÇÃO: Interação medicamentosa é uma importante causa de morbidade mundial. Apresenta especial importância em pacientes oncológicos, pois esses frequentemente estão em uso de polifarmácia, podendo haver interações entre os medicamentos e os quimioterápicos utilizados. OBJETIVO: Avaliar a interação medicamentosa entre a quimioterapia e outros medicamentos em pacientes oncológicos. MÉTODOS: Estudo transversal realizado em serviço ambulatorial de oncologia de um hospital público terciário. Foram incluídos 235 pacientes, identificando-se quais medicamentos eram utilizados por eles. Por meio do auxílio do banco de dados do MedScape e Epocrates, avaliaram-se as interações entre as medicações e os quimioterápicos, definindo sua frequência e dividindo sua gravidade da interação em leve, monitorização próxima e grave. RESULTADOS: Do total estudado, 161 pacientes apresentavam alguma interação medicamentosa, sendo nove tipos de interações leves, 23 tipos de interações com necessidade de monitorização próxima e dois tipos de interações graves. As interações mais frequentes foram entre fluoracil e leucovorin (32 casos) e ciclofosfamida e doxorrubicina (19 casos). As interações sérias foram entre aspirina e pemetrexed; e leucovorim e bactrim. CONCLUSÃO: No presente trabalho, interações medicamentosas foram frequentes, incluindo interações graves com potencial aumento de morbimortalidade. Assim, faz-se necessário que oncologistas tracem um plano terapêutico levando em consideração as possíveis interações medicamentosas entre a quimioterapia prescrita e demais medicações em uso pelos pacientes.