Search

Unhealthy dietary habits can contribute to the development of colorectal cancer (CRC). Such habits may also be associated with post-treatment symptoms experienced by CRC survivors. Therefore, we aimed to assess longitudinal associations of post-treatment unhealthy dietary habits, i.e. intake of ultra-processed foods (UPF), red and processed meat, alcohol and sugar-sweetened drinks, with health-related quality of life (HRQoL), fatigue and chemotherapy-induced peripheral neuropathy (CIPN) in CRC survivors from 6 weeks up to 24 months post-treatment. In a prospective cohort among stage I-III CRC survivors (n 396), five repeated home visits from diagnosis up to 24 months post-treatment were executed. Dietary intake was measured by 7-d dietary records to quantify consumption of UPF, red and processed meat, alcohol and sugar-sweetened drinks. HRQoL, fatigue and CIPN were measured by validated questionnaires. We applied confounder-adjusted linear mixed models to analyse longitudinal associations from 6 weeks until 24 months post-treatment. We applied a post hoc time-lag analysis for alcohol to explore the directionality. Results showed that higher post-treatment intake of UPF and sugar-sweetened drinks was longitudinally associated with worsened HRQoL and more fatigue, while higher intake of UPF and processed meat was associated with increased CIPN symptoms. In contrast, post-treatment increases in alcohol intake were longitudinally associated with better HRQoL and less fatigue; however, time-lag analysis attenuated these associations. In conclusion, unhealthy dietary habits are longitudinally associated with lower HRQoL and more symptoms, except for alcohol. Results from time-lag analysis suggest no biological effect of alcohol; hence, the longitudinal association for alcohol should be interpreted with caution.

BACKGROUND: The increasing colorectal cancer (CRC) survivor population highlights the need for dietary recommendations in order to enhance health-related quality of life (HRQoL) and alleviate symptoms of fatigue, chemotherapy-induced peripheral neuropathy (CIPN) and gastro-intestinal problems.OBJECTIVES: Because of the therapeutic potential of dietary fiber on the gut, we aim to assess longitudinal associations of post-diagnostic dietary fiber, fruit and vegetable intake, a major source of dietary fiber, with HRQoL, fatigue, CIPN and gastro-intestinal symptoms in CRC survivors from 6 weeks to 24 months post-treatment.METHODS: In a prospective cohort among stage I-III CRC survivors (n = 459), five repeated study measurements between diagnosis and 24 months post-treatment were executed. Dietary fiber and fruit and vegetable intake were measured by 7-day dietary records. HRQoL, fatigue, CIPN and gastro-intestinal symptoms were measured by validated questionnaires. We applied confounder-adjusted linear mixed-models to analyze longitudinal associations from 6 weeks until 24 months post-treatment, and used hybrid models to disentangle the overall association into intra-individual changes and inter-individual differences over time.RESULTS: Higher dietary fiber intake, fruit and vegetable intake were longitudinally associated with statistically significant better physical functioning and less fatigue. Intra-individual analyses showed that an increase of 10 g/d in dietary fiber within individuals over time was associated with better physical functioning (β: 2.3; 95% CI: 0.1, 4.4), role functioning (ability to perform daily activities - 5.9; 1.5, 10.3), and less fatigue (-4.1; -7.7,-0.5). An average increase in fruit and vegetable intake of 100 g/d between individuals over time was predominantly associated with less fatigue (-2.2; -4.2,-0.3). No associations were found with CIPN and gastro-intestinal symptoms.CONCLUSION: Our results suggest that increasing dietary fiber, fruit and vegetable intake is related to better physical and role functioning and less fatigue in the first two years after the end of treatment for CRC.Registration: The EnCoRe study was registered at trialregister.nl as NL6904 (former ID: NTR7099).

PURPOSE Proteasome inhibitors are effective in Waldenström's macroglobulinemia (WM) but require parenteral administration and are associated with polyneuropathy. We investigated efficacy and toxicity of the less neurotoxic oral proteasome inhibitor ixazomib combined with rituximab, in patients with relapsed WM. METHODS We conducted a multicenter phase I/II trial with ixazomib, rituximab, and dexamethasone (IRD). Induction consisted of eight cycles IRD wherein rituximab was started in cycle 3, followed by rituximab maintenance. Phase I showed feasibility of 4 mg ixazomib. Primary end point for phase II was overall response rate (ORR [≥ minimal response]) after induction. RESULTS A total of 59 patients were enrolled (median age, 69 years; range, 46-91 years). Median number of prior treatments was 2 (range, 1-7); 70% had an intermediate or high WM-IPSS (International Prognostic Scoring System for WM) score. After eight cycles, ORR was 71% (42 out of 59) (14% very good partial response [PR], 37% PR, and 20% minor response). Depth of response improved until month 12 (best ORR 85% [50 out of 59]: 15% very good PR, 46% PR, and 24% minor response). Median duration of response was 36 months. The average hematocrit level increased significantly (0.33-0.38 L/L) after induction ( P < .001). After two cycles of ixazomib and dexamethasone, immunoglobulin M levels decreased significantly (median 3,700-2,700 mg/dL, P < .0001). Median time to first response was 4 months. Median progression-free survival and overall survival were not reached. After median follow-up of 24 months (range, 7.4-54.3 months), progression-free survival and overall survival were 56% and 88%, respectively. Toxicity included mostly grade 2 or 3 cytopenias, grade 1 or 2 neurotoxicity, and grade 2 or 3 infections. No infusion-related reactions or immunoglobulin M flare occurred with use of subcutaneous rituximab. Quality of life improved significantly after induction. In total, 48 patients (81%) completed at least six cycles of IRD. CONCLUSION Combination of IRD shows promising efficacy with manageable toxicity in patients with relapsed or refractory WM.

DisclaimerThis article is based on recommendations from the 12(th) WALT Congress, Nice, October 3-6, 2018, and a follow-up review of the existing data and the clinical observations of an international multidisciplinary panel of clinicians and researchers with expertise in the area of supportive care in cancer and/or PBM clinical application and dosimetry. This article is informational in nature. As with all clinical materials, this paper should be used with a clear understanding that continued research and practice could result in new insights and recommendations. The review reflects the collective opinion and, as such, does not necessarily represent the opinion of any individual author. In no event shall the authors be liable for any decision made or action taken in reliance on the proposed protocols. Objective: This position paper reviews the potential prophylactic and therapeutic effects of photobiomodulation (PBM) on side effects of cancer therapy, including chemotherapy (CT), radiation therapy (RT), and hematopoietic stem cell transplantation (HSCT). Background: There is a considerable body of evidence supporting the efficacy of PBM for preventing oral mucositis (OM) in patients undergoing RT for head and neck cancer (HNC), CT, or HSCT. This could enhance patients' quality of life, adherence to the prescribed cancer therapy, and treatment outcomes while reducing the cost of cancer care. Methods: A literature review on PBM effectiveness and dosimetry considerations for managing certain complications of cancer therapy were conducted. A systematic review was conducted when numerous randomized controlled trials were available. Results were presented and discussed at an international consensus meeting at the World Association of photobiomoduLation Therapy (WALT) meeting in 2018 that included world expert oncologists, radiation oncologists, oral oncologists, and oral medicine professionals, physicists, engineers, and oncology researchers. The potential mechanism of action of PBM and evidence of PBM efficacy through reported outcomes for individual indications were assessed. Results: There is a large body of evidence demonstrating the efficacy of PBM for preventing OM in certain cancer patient populations, as recently outlined by the Multinational Association for Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). Building on these, the WALT group outlines evidence and prescribed PBM treatment parameters for prophylactic and therapeutic use in supportive care for radiodermatitis, dysphagia, xerostomia, dysgeusia, trismus, mucosal and bone necrosis, lymphedema, hand-foot syndrome, alopecia, oral and dermatologic chronic graft-versus-host disease, voice/speech alterations, peripheral neuropathy, and late fibrosis amongst cancer survivors. Conclusions: There is robust evidence for using PBM to prevent and treat a broad range of complications in cancer care. Specific clinical practice guidelines or evidence-based expert consensus recommendations are provided. These recommendations are aimed at improving the clinical utilization of PBM therapy in supportive cancer care and promoting research in this field. It is anticipated these guidelines will be revised periodically.

Simple Summary Using data from 459 colorectal cancer (CRC) survivors, we described how participants adhered to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) lifestyle recommendations and how this adherence was related to quality of life, level of functioning, symptoms of fatigue, and neuropathy symptoms. We found that increases in a lifestyle score was associated with better physical functioning and less fatigue. No relations with neuropathy symptoms were found. In addition, we observed that physical activity played an important role in the lifestyle score with regards to quality of life. In contrast, we observed that body composition and alcohol recommendations had a counteractive influence within the lifestyle score. Our findings suggest that CRC survivors benefit from overall adherence to the WCRF/AICR lifestyle recommendations in terms of quality of life and fatigue. Specific recommendations have a varying influence on these associations, complicating the interpretation and requiring further study. Abstract Post-treatment adherence to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) lifestyle recommendations were associated with health-related quality of life (HRQoL), fatigue, and chemotherapy-induced peripheral neuropathy (CIPN) in colorectal cancer (CRC) survivors. In a prospective cohort among CRC survivors (n = 459), repeated home-visits were performed at 6 weeks, 6, 12, and 24 months post-treatment. Dietary intake, body composition, sedentary behaviour, and physical activity were assessed to construct a lifestyle score based on adherence to seven 2018 WCRF/AICR recommendations. Longitudinal associations of the lifestyle score with HRQoL, fatigue, and CIPN were analysed by confounder-adjusted linear mixed models. A higher lifestyle score was associated with better physical functioning and less activity-related fatigue, but not with CIPN. Adjustment for physical activity substantially attenuated observed associations, indicating its importance in the lifestyle score with regards to HRQoL. In contrast, adjustment for body composition and alcohol inflated observed associations, indicating that both recommendations had a counteractive influence within the lifestyle score. Our findings suggest that CRC survivors benefit from an overall adherence to the WCRF/AICR lifestyle recommendations in terms of HRQoL and fatigue, but not CIPN. Specific recommendations have a varying influence on these associations, complicating the interpretation and requiring further study.

Patients with multiple myeloma (MM) report high symptom burden and functional disabilities resulting in impaired health-related quality of life (HRQoL). Effective evidence-based rehabilitation guidelines are needed for patients with MM to improve HRQoL. The primary aim of this study was to investigate HRQoL in patients with rehabilitation needs living their everyday life. Patients with MM in remission attended a 12-week multidisciplinary rehabilitation program including a 5-day residential course, home-based exercise and a 2-day follow-up course. The patients were referred by the treating haematologist and completed a booklet of validated HRQoL questionnaires at baseline and before arriving for the 2-day follow-up course. The proportion of participants with moderate to severe symptoms and functional problems were assessed at the two time points and multivariate logistic regression was used to investigate explaining factors of impaired HRQoL at baseline. Ninety-two patients participated with a follow-up compliance rate of 90%. Median age was 67 years and median time since diagnosis was 26 months (ranged 5 months to 15.6 years). The most frequently reported symptoms were global quality of life, role functioning, fatigue, pain, peripheral neuropathy and physical functioning. Pain and fatigue were both highly coherent with impairment in physical functioning and those two symptoms explained most HRQoL impairments. Overall, the participants reported no change in HRQoL after the 12-week rehabilitation program. The study supports the need for an evidence-based guideline for rehabilitation and palliative care to patients with MM in remission living their everyday life.

Background: Colorectal cancer (CRC) survivors need evidence-based guidelines pertaining to post-treatment body composition, which could benefit health-related quality of life (HRQoL). We aimed to describe the course of several body composition measures, and to assess longitudinal associations of these measures with HRQoL, fatigue and chemotherapy-induced peripheral neuropathy (CIPN). Methods: In a prospective cohort among stage I-III CRC survivors (n=459), five repeated home visits from diagnosis up to 24 months post-treatment were executed. Body mass index (BMI), waist circumference and fat percentage were assessed as measures of adiposity, and muscle arm circumference and handgrip strength as measures of muscle mass and function. We applied linear mixed-models to describe changes in body composition over time and to analyze overall longitudinal associations.Results: Of included participants, 44% was overweight and 31% was obese at diagnosis. All body composition measures followed similar trends, decreasing from diagnosis to 6 weeks and then increasing up to 24 months post-treatment. In confounder-adjusted mixed models, increases in adipose tissue and muscle function were longitudinally associated with better HRQoL and less fatigue, regardless of pre-treatment body composition.Discussion: With regards to improving HRQoL, decreasing fatigue and CIPN, clinical practice should also focus on restoring body tissues after CRC treatment.

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.

The World Cancer Research Fund and American Institute for Cancer Research (WCRF/AICR) advise cancer survivors to follow their lifestyle recommendations for cancer prevention. Adhering to these recommendations may have beneficial effects on patient-reported outcomes after a cancer diagnosis, but evidence is scarce. We aimed to assess associations of the individual dietary WCRF/AICR recommendations regarding fruit and vegetables, fibre, fast foods, red and processed meat, sugar-sweetened drinks and alcohol consumption with patient-reported outcomes in colorectal cancer (CRC) survivors. Cross-sectional data of 150 stage I-III CRC survivors, 2-10 years post-diagnosis, were used. Dietary intake was measured by 7-d dietary records. Validated questionnaires were used to measure health-related quality of life (HRQoL), fatigue and neuropathy. Confounder-adjusted linear regression models were used to analyse associations of each WCRF/AICR dietary recommendation with patient-reported outcomes. Higher vegetable intake (per 50 g) was associated with better global QoL (beta 2 center dot 6; 95 % CI 0 center dot 6, 4 center dot 7), better physical functioning (3 center dot 3; 1 center dot 2, 5 center dot 5) and lower levels of fatigue (-4 center dot 5; -7 center dot 6, -1 center dot 4). Higher fruit and vegetables intake (per 100 g) was associated with better physical functioning (3 center dot 2; 0 center dot 8, 5 center dot 5) and higher intake of energy-dense food (per 100 kJ/100 g) with worse physical functioning (-4 center dot 2; -7 center dot 1, -1 center dot 2). No associations of dietary recommendations with neuropathy were found. These findings suggest that adhering to specific dietary WCRF/AICR recommendations is associated with better HRQoL and less fatigue in CRC survivors. Although the recommendations regarding healthy dietary habits may be beneficial for the well-being of CRC survivors, longitudinal research is warranted to gain insight into the direction of associations.

Background The aim of this study was to assess chemotherapy‐induced polyneuropathy (CIPN) 5 years after adjuvant chemotherapy in patients with breast and colorectal cancer. The association of CIPN with quality of life, anxiety, and depression was analyzed. Methods Of a set of 100 patients with breast cancer and of 74 with colorectal cancer who had undergone surgery and adjuvant chemotherapy in 2011‐2012, 80 and 52 patients alive, respectively, were included together with two reference groups of 249 breast cancer patients and 83 colorectal cancer patients who had undergone surgery only. All patients were sent a questionnaire on alcohol consumption, smoking habits, comorbidity, medicine consumption, and oxaliplatin‐specific questions, as well as the Michigan Neuropathy Screening Instrument questionnaire (MNSIq), the Douleur Neuropathique 4 Questions (DN4q), the EQ‐5D, and the Hospital Anxiety and Depression Scale. Possible polyneuropathy was defined as the presence of numbness and/or tingling in the feet, secondly as a score of ≥4 on the MNSIq. Possible painful polyneuropathy was defined as pain in both feet and a score ≥3 on the DN4q. Results The prevalence of possible polyneuropathy defined by numbness and/or tingling in the feet was 38.8% (28.1‐50.3) after adjuvant docetaxel and 57.7% (43.2‐71.3) after adjuvant oxaliplatin, with no significant difference from a previous 1‐year follow‐up (P >.35). Fewer had possible polyneuropathy as defined by the MNSIq. Patients with possible polyneuropathy after adjuvant chemotherapy reported significantly lower quality of life than patients treated with surgery only. Conclusion Symptoms of polyneuropathy following adjuvant docetaxel and oxaliplatin persist 5 years after treatment and affect quality of life negatively., Symptoms of polyneuropathy after adjuvant chemotherapy persist after 1 year. Patient with neuropathy has a lower quality of life

Purpose: Knowledge about long-term colorectal cancer (CRC) or treatment related health and functioning problems and on its impact on participation of CRC survivors in domestic life and in society is limited. We aimed to explore the nature and impact of cancer (treatment) related participation restrictions on everyday life of long-term CRC survivors, their current satisfaction with participation, and associations of health and functioning problems with participation satisfaction, using the International Classification of Functioning, Disability and Health (ICF) to comprehensively study participation.Method: Mixed-method study in 2-10 years post-diagnosis stage I-III CRC survivors (n = 151) from the cross-sectional part of the EnCoRe study. Participation restrictions were explored by semi-structured interviews in a subsample reporting participation restrictions (n = 10). Role functioning (SF36-Health Survey), fatigue (Checklist Individual Strength), and peripheral neuropathy symptoms (EORTC QLQ-CIPN20) were assessed in all participants and associations with self-reported participation satisfaction were analyzed by multivariable logistic regression models.Results: 19% of CRC survivors reported dissatisfaction with participation. Participation restrictions were reported for interpersonal relationships, work/employment, and social/civic life. CRC survivors reporting better physical and emotional role functioning were significantly less likely to be dissatisfied with their participation, whereas survivors reporting higher levels of fatigue or more peripheral neuropathy symptoms were more likely to be dissatisfied with participation.Conclusions: Colorectal cancer (treatment) related health and functioning problems negatively impacts the ability of nearly 1 in 5 long-term CRC survivors to participate in everyday life situations and their satisfaction with participation. Follow-up care needs to be able to identify and address these problems.

We report a series of compounds 1-17 derived from the antiepileptic drug Sulthiame (SLT) from which both the benzenesulfonamide and the sultam moiety were retained. All compounds were tested in vitro for their inhibition activity against the human (h) Carbonic Anhydrase (CA; EC 4.2.1.1) I, II, VII, IX and XII isoforms. Among the series, derivatives 1 and 11 showed great enhancement of both inhibition potency and selectivity towards the hCA VII isoform, when compared to the reference SLT drug. The binding mode of 11 within the hCA VII active site was deciphered by means of X-ray crystallography and revealed the sultam moiety being exposed to the rim of the active site. In vivo experiments on a model of neuropathic pain induced by oxaliplatin clearly showed 11 being an effective pain relieving agent and therefore worth of further exploitation towards the validation of the hCA VII as new target for the management of neuropathies. (C) 2021 Elsevier Masson SAS. All rights reserved., Scientific and Technical Research Council of Turkey [TUBITAK117S516]; Ege University [16-ECZ-012]; Bando di Ateneo per il Finanziamento di Progetti Competitivi per Ricercatori a Tempo Determinato (RTD) dell'Universita di Firenze - 2020-2021; Fondazione Cassa di Risparmio di Firenze [ECR2018.1001], Ozlem Akgul (O.A.) is grateful to The Scientific and Technical Research Council of Turkey [TUBITAK117S516] and Ege University [16-ECZ-012].; Fabrizio Carta (F.C.) is grateful to Bando di Ateneo per il Finanziamento di Progetti Competitivi per Ricercatori a Tempo Determinato (RTD) dell'Universita di Firenze -2020-2021 and Fondazione Cassa di Risparmio di Firenze (Grant Number ECR2018.1001) which partially funded this work.

Purpose of reviewTo discuss cause, clinical manifestations, diagnostics, and treatment of small fiber neuropathy (SFN). The diagnosis is difficult and can be easily missed.Recent findingsSFN causes high morbidity with disabling symptoms and impact on quality of life. Patients may benefit from being diagnosed with SFN, even if no underlying cause is identified and no specific treatment is yet available. Recently, genetic mutations as a possible cause of SFN were identified. Clinical diagnostic criteria have been proposed, but no gold standard exists, and each test has its limitations. The diagnosis requires a combination of typical symptoms, abnormal neurologic findings, and absence of large fiber involvement. Clinicians should be aware of overlapping symptoms of SFN and fibromyalgia. Treatment is often difficult, even when the underlying cause is identified and appropriately treated. Usually, only symptomatic relief of complaints is available.SummaryAwareness of SFN and related symptoms is of great clinical relevance. Guidelines for appropriate diagnostic workup using a stepwise approach involving a combination of tests are warranted. Even if no treatment is available, patients may benefit from timely recognition of SFN.

Paclitaxel, one of the most commonly used cancer chemotherapeutic drugs, effectively extends the progression-free survival of breast, lung, and ovarian cancer patients. However, paclitaxel and other chemotherapy drugs elicit peripheral nerve fiber dysfunction or degeneration that leads to peripheral neuropathy in a large proportion of cancer patients. Patients receiving chemotherapy also often experience changes in mood, including anxiety and depression. These somatic and affective disorders represent major dose-limiting side effects of chemotherapy. Consequently, the present study was designed to develop a preclinical model of paclitaxel-induced negative affective symptoms in order to identify treatment strategies and their underlying mechanisms of action. Intraperitoneal injections of paclitaxel (8 mg/kg) resulted in the development and maintenance of mechanical and cold allodynia. Carboplatin, another cancer chemotherapeutic drug that is often used in combination with paclitaxel, sensitized mice to the nociceptive effects of paclitaxel. Paclitaxel also induced anxiety-like behavior, as assessed in the novelty suppressed feeding and light/dark box tests. In addition, paclitaxel-treated mice displayed depression-like behavior during the forced swim test and an anhedonia-like state in the sucrose preference test. In summary, paclitaxel produced altered behaviors in assays modeling affective states in C57BL/6J male mice, while increases in nociceptive responses were longer in duration. The characterization of this preclinical model of chemotherapy-induced allodynia and affective symptoms, possibly related to neuropathic pain, provides the basis for determining the mechanism(s) underlying severe side effects elicited by paclitaxel, as well as for predicting the efficacy of potential therapeutic interventions. United States Department of Health & Human Services National Institutes of Health (NIH) - USA - R01-CA206028 VCU Massey Cancer Center NIH-NCI Cancer Center Support Grant - P30 CA016059 United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Cancer Institute (NCI) - R01CA206028 - P30CA016059

The course of neuropathic symptoms among elderly patients with stage III colon cancer treated with CAPOX (capecitabine, oxaliplatin), capecitabine, or no chemotherapy was investigated. A total of 117 patients (76%) selected from the Netherlands Cancer Registry completed the first questionnaire. The course of several sensory symptoms was less favorable for patients treated with chemotherapy. Moreover, CAPOX was associated with more symptoms in the toes and feet than was capecitabine.Introduction: Among the elderly, the impairment of functional capacities due to neuropathy can have a significant impact. The aim of the present study was to investigate the course of neuropathic symptoms among elderly patients with stage III colon cancer treated with CAPOX (capecitabine, oxaliplatin), capecitabine monotherapy, or no adjuvant chemotherapy. Materials and Methods: The Netherlands Cancer Registry was used to select patients with stage III colon cancer and aged >= 70 years. Questionnaires were sent after resection (T1) and 6 (T2) and 12 months (T3) later. Neuropathy was measured using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Chemotherapy- Induced Peripheral Neuropathy 20. Logistic generalized estimating equations analyses were used to evaluate the effect of chemotherapy on the course of neuropathic symptoms. Results: Of 155 eligible patients, 117 (76%) completed the T1 questionnaire, and 69 and 59 completed the T2 and T3 questionnaires, respectively. The course of the sensory symptoms tingling fingers or hands, tingling toes or feet, numbness in fingers or hands, and numbness in toes or feet was significantly unfavorable for patients treated with adjuvant chemotherapy (CAPOX or capecitabine) compared with that for patients who had not received adjuvant chemotherapy. The course of numbness in toes or feet also differed significantly between patients treated with CAPOX (T1, 7%; T2, 50%; T3, 42%) and patients treated with capecitabine (T1, 17%; T2, 31%; T3, 8%). Additionally, patients treated with capecitabine reported significantly less tingling toes or feet (T1, 6%; T2, 25%; T3, 7%) compared with patients treated with CAPOX (T1, 0%; T2, 50%; T3, 58%). Conclusion: The course of several sensory symptoms over time was less favorable for elderly patients with colon cancer treated with chemotherapy. Moreover, CAPOX was associated with more symptoms in toes and feet compared with capecitabine. It is important to inform patients of these risks to enable informed decision-making.

The aim of this analysis is to assess (1) self-reported chemotherapy-induced peripheral neuropathy (CIPN) symptoms; (2) its association with sociodemographic and clinical characteristics; and (3) treatment dose modifications and its influence on the magnitude of neurotoxicity in a population-based cohort of patients with multiple myeloma (MM). MM patients (n = 156), diagnosed between 2000 and 2014, filled out the EORTC QLQ-CIPN20 (65% response). Data on treatment, outcomes, and dose modifications were extracted from the medical files. Fifty-three percent of patients reported at least one and on average three neuropathy symptoms that bothered them the most during the past week, with tingling toes/feet as most reported. In multivariate analysis, thalidomide, especially higher cumulative dose, was associated with neuropathy (beta = 0.26, CI 95% 0.27-15.34, p = 0.04) and CIPN was not associated with age, sex, time since last course of therapy, number of prior therapies, osteoarthritis, or diabetes. Dose modifications were often applied (65%). Although not statistically significant, a trend towards higher sensory (22 vs. 15 vs. 12, p = 0.22) and motor neuropathy scores (21 vs. 15 vs. 11, p = 0.36) was observed among patients receiving dose modification because of CIPN (31%) compared to those receiving a dose modification for another reason or no dose modification, without altering treatment response. CIPN is a common dose limiting side effect in patients with MM. Severity of CIPN was mainly affected by treatment with thalidomide. In spite of dose modifications, patients still reported somewhat higher neuropathy scores without altered response rates. Early dose modification based on a more reliable tool for CIPN measurements may prove value.

Germ cell testicular cancer (TC) represents a malignancy with high cure rates. Since the introduction of cisplatin-based chemotherapy in the late 1970s, the 5-year survival rate has increased considerably, and it is currently above 95%. Because TC is usually diagnosed before the age of 40 years, these men can expect to live for another 40 to 50 years after being successfully treated. This success, however, is hampered by an increased risk of long-term and late effects of treatment. Secondary malignant neoplasms and cardiovascular disease represent the most common potentially life-threatening late effects, typically occurring more than 10 years after treatment. Other long-term effects include pulmonary toxicity, nephrotoxicity, neurotoxicity, decreased fertility, hypogonadism, and psychosocial problems. The incidence and time to onset of these various adverse effects vary according to treatment type and intensity. There is still little knowledge about underlying mechanisms and genetic susceptibility of the various adverse effects. Apart from treatment burden, it is not yet possible to identify patients who are at high risk for certain late effects after TC treatment. In this clinical review, we present the current status regarding different somatic and psychosocial long-term late effects after treatment for TC, based on Medline searches and our own research. Moreover, we postulate recommendations for general medical evaluations that should begin after treatment is completed and continue during follow-up.

Context. Persistent pain after treatment for breast cancer (PPBCT) is a common side effect of breast cancer treatment, with prevalence as high as 50%. It is predominantly a neuropathic condition. Objectives. The aim of this cross-sectional, questionnaire-based study was to examine the emotional characteristics of patients with PPBCT in long-term breast cancer patients. A secondary objective was to characterize the risk factors and severity of that pain. Methods. From March 1, 2010 to April 9, 2010, long-term follow-up patients were invited to complete a questionnaire. This recorded their surgical and demographic data and ascertained whether they had PPBCT. If the patient had pain, she completed a range of validated self-report questionnaires and questions about the nature of the pain, including a visual analogue scale. Results. One hundred eleven patients completed the questionnaire; 33 (29.7%) patients reported chronic pain at a median time of 64 months postoperatively (interquartile range 54.25). Patients with persistent pain were not significantly more anxious (t(105) = 0.369, P = 0.713) or depressed (t(105) = 0.713, P = 0.507) than patients without pain. Patients with constant pain compared with intermittent pain were significantly more anxious (t(25) = 3.460, P = 0.002). Preoperative pain conferred a fivefold increased risk of PPBCT (odds ratio [OR] = 5.17, 95% confidence interval [CI] = 1.79-14.97, P = 0.002); chemotherapy conferred a threefold increased risk (OR = 3.004, 95% CI = 1.22-7.40, P = 0.017). Conclusion. We have shown significant numbers of patients suffer from PPBCT. At a median time of 64.5 months, women with pain are not significantly more anxious or depressed than women without pain. Preoperative pain and chemotherapy have been highlighted as risk factors.

Background: Oxaliplatin chemotherapy induced neuropathy is a dose related cumulative toxicity that manifests as tingling, numbness, and chronic pain, compromising the quality of life and leading to discontinued chemotherapy. Patients report marked hypersensitivity to cold stimuli at early stages of treatment, when sensory testing reveals cold and heat hyperalgesia. This study examined the morphological and functional effects of oxaliplatin treatment in cultured adult rat DRG neurons. Results: 48 hour exposure to oxaliplatin resulted in dose related reduction in neurite length, density, and number of neurons compared to vehicle treated controls, using Gap43 immunostaining. Neurons treated acutely with 20 μg/ml oxaliplatin showed significantly higher signal intensity for cyclic AMP immunofluorescence (160.5 ± 13 a.u., n = 3, P < 0.05), compared to controls (120.3 ± 4 a.u.). Calcium imaging showed significantly enhanced capsaicin (TRPV1 agonist), responses after acute 20 μg/ml oxaliplatin treatment where the second of paired capsaicin responses increased from 80.7 ± 0.6% without oxaliplatin, to 171.26 ± 29% with oxaliplatin, (n = 6 paired t test, P < 0.05); this was reduced to 81.42 ± 8.1% (P < 0.05), by pretretreatment with the cannabinoid CB2 receptor agonist GW 833972. Chronic oxaliplatin treatment also resulted in dose related increases in capsaicin responses. Similarly, second responses to icilin (TRPA1/TRPM8 agonist), were enhanced after acute (143.85 ± 7%, P = 0.004, unpaired t test, n = 3), and chronic (119.7 ± 11.8%, P < 0.05, n = 3) oxaliplatin treatment, compared to control (85.3 ± 1.7%). Responses to the selective TRPM8 agonist WS-12 were not affected. Conclusions: Oxaliplatin treatment induces TRP sensitization mediated by increased intracellular cAMP, which may cause neuronal damage. These effects may be mitigated by co-treatment with adenylyl cyclase inhibitors, like CB2 agonists, to alleviate the neurotoxic effects of oxaliplatin.

Chemotherapy-induced neuropathic pain is a debilitating and common side effect of cancer treatment. Mitochondrial dysfunction associated with oxidative stress in peripheral nerves has been implicated in the underlying mechanism. We investigated the potential of melatonin, a potent antioxidant that preferentially acts within mitochondria, to reduce mitochondrial damage and neuropathic pain resulting from the chemotherapeutic drug paclitaxel. In vitro, paclitaxel caused a 50% reduction of mitochondrial membrane potential and metabolic rate, independent of concentration (20-100μM). Mitochondrial volume was increased dose-dependently by paclitaxel (200% increase at 100μM). These effects were prevented by co-treatment with 1μM melatonin. Paclitaxel cytotoxicity against cancer cells was not affected by co-exposure to 1μM melatonin of either the breast cancer cell line MCF-7, or the ovarian carcinoma cell line A2780. In a rat model of paclitaxel-induced painful peripheral neuropathy, pre-treatment with oral melatonin (5/10/50mg/kg), given as a daily bolus dose, was protective, dose-dependently limiting development of mechanical hypersensitivity (19/43/47% difference from paclitaxel control, respectively). Melatonin (10mg/kg/day) was similarly effective when administered continuously in drinking water (39% difference). Melatonin also reduced paclitaxel-induced elevated 8-isoprostane F2 α levels in peripheral nerves (by 22% in sciatic; 41% in saphenous) and limited paclitaxel-induced reduction of C fibre activity-dependent slowing (by 64%). Notably melatonin limited the development of mechanical hypersensitivity in both male and female animals (by 50/41%, respectively) and an additive effect was found when melatonin was given with the current treatment, duloxetine (75/62% difference, respectively). Melatonin is therefore a potential treatment to limit the development of painful neuropathy resulting from chemotherapy treatment. This article is protected by copyright. All rights reserved.

PURPOSE OF REVIEW: To discuss cause, clinical manifestations, diagnostics, and treatment of small fiber neuropathy (SFN). The diagnosis is difficult and can be easily missed. RECENT FINDINGS: SFN causes high morbidity with disabling symptoms and impact on quality of life. Patients may benefit from being diagnosed with SFN, even if no underlying cause is identified and no specific treatment is yet available. Recently, genetic mutations as a possible cause of SFN were identified. Clinical diagnostic criteria have been proposed, but no gold standard exists, and each test has its limitations. The diagnosis requires a combination of typical symptoms, abnormal neurologic findings, and absence of large fiber involvement. Clinicians should be aware of overlapping symptoms of SFN and fibromyalgia. Treatment is often difficult, even when the underlying cause is identified and appropriately treated. Usually, only symptomatic relief of complaints is available. SUMMARY: Awareness of SFN and related symptoms is of great clinical relevance. Guidelines for appropriate diagnostic workup using a stepwise approach involving a combination of tests are warranted. Even if no treatment is available, patients may benefit from timely recognition of SFN.

Linked ArticlesThis article is part of a themed section on Cannabinoids 2013. To view the other articles in this section, see Fagan and Campbell (2014) DOI: , Ignatowska-Jankowska etal. (2014) DOI: , Ligresti etal. (2014) DOI: , Lopez-Rodriguez etal. (2014) DOI: , Murataeva etal. (2014) DOI: , Okine etal. (2014) DOI: , Rodriguez-Cueto etal. (2014) DOI: , Stanley and O'Sullivan (2014) DOI: , Toguri etal. (2014) DOI: , Wu etal. (2014) DOI: . Linked articles are: Avraham etal. (2014) DOI: , Machado etal. (2014) DOI: , Ward etal. (2014) DOI: .