Treatment-related Side Effects Research Articles

"Your Body Is Not At All Where You Left It": Adolescent and Young Adult Cancer Survivors' Experiences Transitioning Back Into Physical Activity After Treatment.

Physical activity (PA) can help manage cancer treatment-related side effects and improve well-being following treatment; however, resuming PA after a period of inactivity due to cancer can be challenging. The purpose of this study was to explore adolescents and young adults (AYAs) experiences transitioning back into PA after a period of inactivity due to cancer treatment. Twelve previously active AYAs (Mage = 30 ± 5.8 years) were purposefully sampled and engaged in a semi-structured interview. The following four themes were generated through a reflexive thematic analysis: PA is described as important and valuable; navigating one's appearance and fitness changes after cancer treatment within the PA context; supportive care is essential to successful PA transitions; and juxtaposed environments: fitness facilities, cities, and green spaces. Developing strategies aimed at gradually transitioning into PA should be a priority to improve AYAs' well-being through survivorship.

Combination Neoantigen-Based Dendritic Cell Vaccination and Adoptive T-Cell Transfer Induces Antitumor Responses Against Recurrence of Hepatocellular Carcinoma.

A high rate of recurrence after curative therapy is a major challenge for the management of hepatocellular carcinoma (HCC). Currently, no effective adjuvant therapy is available to prevent HCC recurrence. We designed a personalized neoantigen-loaded dendritic cell vaccine and neoantigen-activated T-cell therapy, and used it as adjuvant therapy to treat 10 patients with HCC who had undergone curative resection or radiofrequency ablation in the first stage of a phase II trial (NCT03067493). The primary outcomes were safety and neoantigen-specific immune response. Disease-free survival (DFS) was also evaluated. The immunotherapy was successfully administered to all the patients without unexpected delay and demonstrated a reasonable safety profile with no grade ≥3 treatment-related side effects reported. Seventy percent of patients generated de novo circulating multiclonal neoantigen-specific T-cell responses. Induced neoantigen-specific immunity was maintained over time, and epitope spreading was observed. Patients who generated immune responses to treatment exhibited prolonged DFS compared with nonresponders (P = 0.012), with 71.4% experiencing no relapse for 2 years after curative treatment. High expression of an immune stimulatory signature, enhanced immune-cell infiltration (i.e., CD8+ T cells), and upregulated expression of T-cell inflammatory gene profiles were found in the primary tumors of the responders. In addition, neoantigen depletion (immunoediting) was present in the recurrent tumors compared with the primary tumors (7/9 vs. 1/17, P = 0.014), suggesting that immune evasion occurred under the pressure of immunotherapy. Our study indicates that neoantigen-based combination immunotherapy is feasible, safe, and has the potential to reduce HCC recurrence after curative treatment.

P303 Development of a Behçet’s disease specific patient concerns inventory

Abstract Background/Aims Behçet’s Disease (BD) is a rare multi-system variable vessel vasculitis. It is characterised by oral ulcers, genital ulcers and ocular involvement; however, expression can vary, with patients experiencing a range of symptoms affecting several body systems. This creates the need for an individual and holistic approach to management in order to optimise patient care. A patient concerns inventory (PCI) is a validated tool used to encourage patient-led reviews by exploring areas of concern and unmet needs, and has shown to increase patient satisfaction in oncology and rheumatology consultations. The aim of this study was to develop a novel BD-specific PCI and to assess the impact of this tool in clinic following ethical approval. Methods Phase I: Literature search conducted to identify concerns and areas of unmet need in BD patients to create an initial PCI across four separate domains, including physical and functional well-being, psychological and emotional well-being, social care and social well-being, and treatment related side effects. Phase II: PCI presented to the BD multi-disciplinary team for feedback and refinement. Members were asked to rate each item based on how frequently that issue was discussed in consultations, from ‘never’, to ‘sometimes’, ‘most of the times’ or ‘every time’. Phase III: Updated version of PCI presented to patient groups in association with Behçet’s Society UK. Patients were asked to rate on an identical scale. Collective feedback allowed for a final version of the PCI to be created. Phase IV: Pilot study to test the effectiveness of the PCI in BD clinics. Pre- and post-PCI groups will be created. The mean differences in consultation time, number of concerns and patient satisfaction will be compared. Results Phase I: Following the application of an inclusion and exclusion criteria, 35 papers yielded a total of 54 items for the initial PCI. Phase II: 12 responses were received, which led to the exclusion of 9 items based on 60% of the respondents reporting this issue was ‘never’ discussed in clinic. A total of 2 items were added, which led to a 47-item PCI. Phase III: 239 responses received from BD patients. 3 items eliminated and 4 added on. Final 48-version PCI created. Phase IV: Pilot study will commence following ethical approval. Conclusion A PCI is a holistic tool used to improve communication and encourage patient-led consultations. Phases I to III have led to the creation of a 48-item BD-specific PCI which will be tested in clinic as a pilot following ethical approval. We hope to demonstrate an increase in patient satisfaction following the introduction of a PCI in BD clinics. Disclosure S. Mukhtar: None. R. Moots: None.

Review: Neurological Complications From Therapies for Pediatric Brain Tumors.

Surgery, chemotherapy and radiation have been the mainstay of pediatric brain tumor treatment over the past decades. Recently, new treatment modalities have emerged for the management of pediatric brain tumors. These therapies range from novel radiotherapy techniques and targeted immunotherapies to checkpoint inhibitors and T cell transfer therapies. These treatments are currently investigated with the goal of improving survival and decreasing morbidity. However, compared to traditional therapies, these novel modalities are not as well elucidated and similarly has the potential to cause significant short and long-term sequelae, impacting quality of life. Treatment complications are commonly mediated through direct drug toxicity or vascular, infectious, or autoimmune mechanisms, ranging from immune effector cell associated neurotoxicity syndrome with CART-cells to neuropathy with checkpoint inhibitors. Addressing treatment-induced complications is the focus of new trials, specifically improving neurocognitive outcomes. The aim of this review is to explore the pathophysiology underlying treatment related neurologic side effects, highlight associated complications, and describe the future direction of brain tumor protocols. Increasing awareness of these neurologic complications from novel therapies underscores the need for quality-of-life metrics and considerations in clinical trials to decrease associated treatment-induced morbidity.

Outcome after Radiotherapy for Vestibular Schwannomas (VS)-Differences in Tumor Control, Symptoms and Quality of Life after Radiotherapy with Photon versus Proton Therapy.

Simple SummaryThe standard of care for radiotherapy of symptomatic or progressive vestibular schwannomas (VS) is photon beam single-dose radiosurgery (applying 1 × 12 Gy) or (hypo)fractionated radiotherapy (applying 3 × 6 Gy up to 32 × 1.8 Gy). Only few centers also enable irradiation with protons. Proton therapy offers unique physical properties whereby healthy tissue around the tumor can be protected although a very high dose is applied to the target lesion. In patients with benign brain tumors such as vestibular schwannomas reduction of treatment-related side effects is very important. Few data comparing photon vs. proton beam radiotherapy for patients with VS are available. Thus, a detailed evaluation of differences in tumor control, symptoms and quality of life in patients with VS after photon beam vs. proton beam radiotherapy is needed.Background: To evaluate differences in local tumor control (LC), symptoms and quality of life (QOL) of 261 patients with VS after stereotactic radiosurgery/hypofractionated stereotactic radiotherapy (SRS/HFSRT) vs. fractionated radiotherapy (FRT) vs. fractionated proton therapy (FPT) were studied. Methods: For SRS/HFSRT (n = 149), the median fraction dose applied was 12 Gy. For FRT (n = 87) and FPT (n = 25), the median cumulative doses applied were 57.6 Gy and 54 Gy (RBE), respectively. FRT and FPT used single median doses of 1.8 Gy/Gy (RBE). Median follow-up was 38 months. We investigated dosimetry for organs at risk and analyzed toxicity and QOL by sending out a questionnaire. Results: LC was 99.5% at 12 months after RT with no statistical difference between treatment groups (p = 0.19). LC was significantly lower in NF2 patients (p = 0.004) and in patients with higher tumor extension grade (p = 0.039). The hearing preservation rate was 97% at 12 months after RT with no statistical difference between treatment groups (p = 0.31). Facial and trigeminal nerve affection after RT occurred as mild symptoms with highest toxicity rate in FPT patients. Conclusion: SRS/HFSRT, FRT and FPT for VS show similar overall clinical and functional outcomes. Cranial nerve impairment rates vary, potentially due to selection bias with larger VS in the FRT and FPT group.

Nutrition Impact Symptoms in Relation to Head and Neck Cancer Survivor’s Vegetable Intake and Use of Seasoning

Background: Most head and neck cancer (HNC) patients undergoing aggressive treatments with chemoradiotherapy and surgical resection of tumors suffer from symptoms long after treatment is completed that hinder adequate oral food intake, collectively known as Nutrition Impact Symptoms (NIS). Our aim was to examine the correlations between NIS and HNC survivors’ vegetable intake and use of seasoning. Methods: We conducted a 29-item telephone administrated survey to collect vegetable intake and seasoning habits among HNC survivors (n=22, age 61.4 ± 9.8 years, mean ± standard deviation) who received radiation therapy between 6 months and 10 years before recruitment identified through the cancer registry at Carle Foundation Hospital. Treatment-related side-effects (11 items) including difficulty swallowing, dry mouth, and mouth sores reflected NIS. A mean composite score was created for all the symptoms where higher scores indicated greater NIS. Spearman correlations examined the relationships between NIS, vegetable intake, and seasoning. Results: Half (50%) of the participants reported no change in their vegetable intake since diagnosis of cancer, and on average, ate 1 cup/day of total vegetables. Higher NIS scores associated with higher pumpkin and sweet potatoes intake (r (20) = .43, p<0.05), and there was a trend for higher scores of difficulties swallowing to be associated with lower corn and peas intake (r (20) =-.37, p=0.08). Participants with higher scores of problems with teeth and gums were less likely to use seasoning (r (20) = -.42, p<0.05). Conclusion: The findings support that HNC treatment can affect vegetable intake long after completion of radiotherapy. However, it would be premature for any recommendations to be derived from the present study for health professionals. A larger, observational study with a longer follow-up is therefore needed to examine these correlations.

Systemic Treatment of Soft Tissue Sarcomas in the Geriatric Population.

As the population ages, there will be an increase in the incidence and prevalence of soft tissue sarcoma (STS) within the geriatric population. As this disease disproportionately affects older adults, the percentage of adults >65 years old is expected to increase in the coming years. Geriatric patients are often more vulnerable to disease-related symptoms and have more difficulty tolerating treatment-related side effects. While there are no formal existing guidelines to direct the care of this geriatric patient population, it is of utmost importance to consider each patients' fitness and co-morbidities when selecting treatment plans. This review focuses on the current state of research of older adults with advanced or metastatic soft tissue sarcoma, highlighting the lack of representation of this patient population in clinical trials. Given that chronological age does not necessarily equate to physiologic age, integration of comprehensive geriatric and quality of life assessments is needed in the care of geriatric patients to help guide therapeutic decisions.

Pan-Genotypic Direct-Acting Antiviral Agents for Undetermined or Mixed-Genotype Hepatitis C Infection: A Real-World Multi-Center Effectiveness Analysis.

Although the pan-genotypic direct-acting antiviral regimen was approved for treating chronic hepatitis C infection regardless of the hepatitis C virus (HCV) genotype, real-world data on its effectiveness against mixed-genotype or genotype-undetermined HCV infection are scarce. We evaluated the real-world safety and efficacy of two pan-genotypic regimens (Glecaprevir/Pibrentasvir and Sofosbuvir/Velpatasvir) for HCV-infected patients with mixed or undetermined HCV genotypes from the five hospitals in the Changhua Christian Care System that commenced treatment between August 2018 and December 2020. This retrospective study evaluated the efficacy and safety of pan-genotypic direct-acting antiviral (DAA) treatment in adults with HCV infection. The primary endpoint was the sustained virological response (SVR) observed 12 weeks after completing the treatment. Altogether, 2446 HCV-infected patients received the pan-genotypic DAA regimen, 37 (1.5%) patients had mixed-genotype HCV infections and 110 (4.5%) patients had undetermined HCV genotypes. The mean age was 63 years and 55.8% of our participants were males. Nine (6.1%) patients had end-stage renal disease and three (2%) had co-existing hepatomas. We lost one patient to follow-up during treatment and one more patient after treatment. A total of four patients died. However, none of these losses were due to treatment-related side effects. The rates of SVR12 for mixed-genotype and genotype-undetermined infections were 97.1% and 96.2%, respectively, by per-protocol analyses, and 91.9% and 92.7% respectively, by intention-to-treat population analyses. Laboratory adverse events with grades ≥3 included anemia (2.5%), thrombocytopenia (2.5%), and jaundice (0.7%). Pan-genotypic DAAs are effective and well-tolerated for mixed-genotype or genotype-undetermined HCV infection real-world settings.

Hormonal Therapy Drug Switching, Out-of-Pocket Costs, and Adherence Among Older Women With Breast Cancer.

Adherence to aromatase inhibitors (AIs) and tamoxifen has considerable survival benefits for postmenopausal women diagnosed with hormone receptor-positive breast cancer. Reduced out-of-pocket costs and treatment-related side effects could increase therapy adherence. Given that individuals' side effect profiles could differ across AIs, generic AI entry could facilitate switching between AIs to manage side effects and improve adherence. From Surveillance, Epidemiology, and End Results-Medicare, we selected women first diagnosed with hormone receptor-positive breast cancer at age 65+ years and initiated an AI within 1 year of diagnosis between January 1, 2007, and May 31, 2008, or June 1, 2011, and December 31, 2012, and followed them for up to 2 years (N = 20 677). We estimated changes in probabilities of adherence withand without switching for Part D enrollees with and without the low-income subsidy (LIS vs non-LIS) before and after genericentry using linear probability models. Tests of statistical significance are 2-sided. After generic entry reduced out-of-pocket costs of AIs (larger reduction for non-LIS), the percentage of women who ever switched from one AI to another AI increased from 8.8% to 14.6% for non-LIS and from 7.3% to 12.5% for LIS. Adherence without switching increased by 8.0 percentage points (pp) for non-LIS (P < .001) but decreased by 4.9 pp (P < .001) for LIS. Adherence with switching increased for both non-LIS (6.4 pp, P < .001) and LIS (4.4 pp, P < .001). Increased switching after generic entry contributed to increased adherence, suggesting switching allowed better management of treatment-related side effects. Subsidized women also experienced increased adherence with switching after generic entry, suggesting that patients and physicians might not understand Part D benefit design when making decisions.

MnTE-2-PyP protects fibroblast mitochondria from hyperglycemia and radiation exposure

Radiation is a common anticancer therapy for prostate cancer, which transforms tumor-associated normal fibroblasts to myofibroblasts, resulting in fibrosis. Oxidative stress caused by radiation-mediated mitochondrial damage is one of the major contributors to fibrosis. As diabetics are oxidatively stressed, radiation-mediated reactive oxygen species cause severe treatment failure, treatment-related side effects, and significantly reduced survival for diabetic prostate cancer patients as compared to non-diabetic prostate cancer patients. Hyperglycemia and enhanced mitochondrial damage significantly contribute to oxidative damage and disease progression after radiation therapy among diabetic prostate cancer patients. Therefore, reduction of mitochondrial damage in normal prostate fibroblasts after radiation should improve the overall clinical state of diabetic prostate cancer patients. We previously reported that MnTE-2-PyP, a manganese porphyrin, reduces oxidative damage in irradiated hyperglycemic prostate fibroblasts by scavenging superoxide and activating NRF2. In the current study, we have investigated the potential role of MnTE-2-PyP to protect mitochondrial health in irradiated hyperglycemic prostate fibroblasts. This study revealed that hyperglycemia and radiation increased mitochondrial ROS via blocking the mitochondrial electron transport chain, altered mitochondrial dynamics, and reduced mitochondrial biogenesis. Increased mitochondrial damage preceeded an increase in myofibroblast differentiation. MnTE-2-PyP reduced myofibroblast differentiation, improved mitochondrial health by releasing the block on the mitochondrial electron transport chain, enhanced ATP production efficiency, and restored mitochondrial dynamics and metabolism in the irradiated-hyperglycemic prostate fibroblasts. Therefore, we are proposing that one of the mechanisms that MnTE-2-PyP protects prostate fibroblasts from irradiation and hyperglycemia-mediated damage is by protecting the mitochondrial health in diabetic prostate cancer patients.

Stereotactic ablative radiotherapy for pulmonary oligometastases from primary hepatocellular carcinoma: a multicenter and retrospective analysis (KROG 17-08).

Hypofractionated radiotherapy has recently been applied to treat pulmonary metastases of hepatocellular carcinoma. However, there is no definite evidence on its safety and efficacy. We evaluate the clinical outcomes of hypofractionated radiotherapy for oligo pulmonary metastases of hepatocellular carcinoma in the multicenter and retrospective study. From March 2011 to February 2018, 58 patients with fewer than five pulmonary metastases of hepatocellular carcinoma who underwent hypofractionated radiotherapy in nine tertiary university hospitals were analyzed retrospectively. The primary endpoint was the local control rate. The secondary endpoints were overall survival, progression-free survival, prognostic factors affecting the treatment outcomes and treatment-related side effects. The local tumor response rate including complete and partial response was 77.6% at 3months after hypofractionated radiotherapy. The median survival and progression-free survival times were 20.9 and 5.3months, respectively. The 1-year overall survival and progression-free survival rates were 65.5 and 22.4%, respectively. The good treatment response after hypofractionated radiotherapy (P=0.001), the absence of intrahepatic tumor (P=0.004) and Child-Pugh class A (P=0.010) were revealed as significant prognostic factors for overall survival in the multivariate analysis. A progression-free interval of <6months (P=0.009) was a negative prognostic factor for overall survival in the multivariate analysis. Of 58 patients, five (8.6%) had grade 2 or higher radiation pneumonitis after hypofractionated radiotherapy. The favorable local control rate and acceptable toxicity indicate the clinical usefulness of hypofractionated radiotherapy for hepatocellular carcinoma patients who have less than five pulmonary metastases.

A Randomised, Comparative, Effectiveness Trial Evaluating Low- versus High-Level Supervision of an Exercise Intervention for Women with Breast Cancer: The SAFE Trial.

Simple SummaryThe compelling evidence demonstrating the benefits of exercise to cancer survivors is biased towards ‘more well’ patients undertaking exercise interventions in tightly controlled (highly supervised) conditions. The aim of this trial was to evaluate the safety, feasibility, and effect of a 12-week exercise intervention delivered under ‘real-world’ conditions (that is, with low-level supervision, defined as five sessions across 12 weeks) compared with the same exercise intervention delivered under high-level supervision (20 sessions across 12 weeks). The understudied, less well women with breast cancer were the target population; that is, women with stage II or higher disease at diagnosis, and at least one comorbidity or treatment-related side-effect. The results showed that exercise was safe and feasible for this understudied breast cancer subgroup, and, while women who received the exercise intervention with low-level supervision experienced improvements in quality of life and physical function, greater gains in strength and exercise self-efficacy were observed for women who had the exercise intervention delivered via high-level supervision. Future research will determine whether the extra benefit gained through higher supervision levels lead to longer term quality of life and survival benefits.The aim of this comparative, effectiveness trial was to evaluate the safety, feasibility and effect of an exercise intervention delivered via low-level versus high-level supervision. The target population were women who were diagnosed with ≥stage II breast cancer, had ≥ one comorbidity and/or persistent treatment-related side-effects, and were insufficiently physically active. Sixty women (50 ± 9 years) were randomized to the low-supervision group (n = 30) or high-supervision group (n = 30). The low-supervision group participated in a 12-week, individually-tailored exercise intervention supported by five supervised sessions with an exercise professional. The high-supervision group participated in the same exercise intervention but received 20 supervised sessions across the 12-week period. The target weekly dosage of 600 metabolic equivalent minutes of exercise per week (MET-mins/wk) and the session content, such as safety and behaviour change topics, were standardized between the groups. The primary outcomes were intervention safety, defined as the number, type, and severity of exercise-related adverse events (e.g., musculoskeletal injury or exacerbated treatment-related side effects), and feasibility, which was defined as compliance to target exercise dosage. The effect of the intervention on quality of life, physical activity, self-efficacy, fitness, and strength was also assessed (pre- and post-intervention, and at 12-week follow-up). The intervention was safe, with no exercise-related adverse events of grade 3 or above in either group. Both groups reported high compliance to the target exercise dosage (median MET-mins/wk: High = 817; Low = 663), suggesting the exercise intervention was feasible, irrespective of supervision level. Improvements in quality of life, physical activity and fitness were observed post-intervention and maintained at follow-up for both groups (p < 0.05). Only the high-supervision group showed clinically-relevant improvements in strength and self-efficacy at post-intervention (p < 0.05). Individually-targeted exercise delivered under high- or low-levels of supervision is safe, feasible and beneficial for women with stage II+ breast cancer. Future research needs to assess whether the greater gains observed in the group who received higher supervision may contribute to longer term maintenance of physical activity levels and overall health benefits. Australian and New Zealand Clinical Trials Registry: ACTRN12616000547448.

Disease Control after Radiotherapy for Adult Craniopharyngioma: Clinical Outcomes from a Large Single-Institution Series.

To report disease control and treatment-related side effects among adult patients with craniopharyngioma treated with radiotherapy. We performed a single-institution review of adult patients (> 21years old) with craniopharyngioma treated with radiotherapy either definitively or postoperatively for gross residual disease. We report disease control, survival, and radiotherapy-related side effects. A total of 49 adult patients with craniopharyngioma were included, 27 of whom were treated at initial presentation and 22 for recurrent disease following initial surgery and observation. Overall, 77% received radiotherapy postoperatively (either after primary surgery or surgery for recurrence). With a median clinical and radiographic follow-up of 4.2 (range, 0.4-21.6) years and 3.0 (range, 0-21.5) years, the 5- and 10-year local control rates were 100 and 94%, respectively. The 5- and 10-year overall survival rates were 80 and 66%, respectively. Eleven percent of patients experienced grade 2 vision deterioration and 18% suffered grade 2 endocrinopathies following radiotherapy. Radiotherapy provides excellent disease control with acceptable toxicity among adult patients with craniopharyngioma. These data support the use of fractionated radiotherapy in adult patients with recurrent or gross residual disease after surgery. For inoperable patients or those with moderate or high surgical risk to neurologic and/or vascular structures, we advocate for limited surgical resection and postoperative radiotherapy to balance optimal tumor control with tumor- and treatment-related morbidity.

Radiotherapy for vertebral hemangioma: the single-center experience of 80patients.

This study aimed to evaluate the therapeutic effect of radiotherapy and to determine possible prognostic factors in patients with painful vertebral hemangioma. In the last two decades, 80patients with vertebral hemangioma who received radiotherapy in our institute were evaluated in terms of pain response, treatment-related side effects, and prognostic factors. All patients were questioned 3months after radiotherapy for the evaluation of pain response and were divided into threegroups (complete response, partial response, and no change). Moreover, the visual analog scale (VAS) was used for pain response assessment in 46patients. Pain status was assessed to detect recurrence at each clinical examination during the follow-up period. Possible prognostic factors such as gender, size of the hemangioma, location, multilevel involvement and additional musculoskeletal disease on pain response were analyzed. In this study, 45individuals had lesions in the lumbar spine, 28in the thoracic, and 7in the cervical region. Furthermore, 51patients had additional musculoskeletal conditions such as disc herniation, degenerative diseases, spondylolisthesis, and compression fracture. Radiotherapy was performed with amedian daily dose of 2 Gy and amedian total dose of 40 Gy. Complete pain response occurred in 58.8% of patients, 26.2% of patients had partial pain response, and 15% of patients had no pain response. The overall response rate was 85%, and 7patients showed recurrent pain symptoms in the overall response group at routine follow-up. Additional musculoskeletal disorders were found to be the only prognostic factor associated with pain response. The median follow-up time was 60months. Secondary malignancy was not found in any of the patients in this short follow-up time. No acute or late radiation-associated side effects greater than gradeII were observed. To our best knowledge, this study is one of the largest single-institution radiotherapy series on vertebral hemangiomas reported to date. The obtained data support the efficacy and safety of radiotherapy in the treatment of painful vertebral hemangioma. Our study showed that additional musculoskeletal disease plays an important role in pain response. Other prognostic factors and treatment of vertebral hemangioma with stereotactic radiosurgery should be investigated in future studies.

Diaphragm thickness, mobility and respiratory muscle strength in patients with head and neck cancer receiving chemoradiation therapy: A longitudinal pilot study

Background: Head and neck cancer is the sixth most common cancer worldwide and is also associated with many pulmonary complications. Decreased cardiopulmonary function and functional capacity is one of the major treatment related side effects of chemoradiation therapy. In this study we aimed to assess and quantify the impact of treatment related side effects on the respiratory function and functional capacity of head and neck cancer patients during chemoradiation therapy. Methods: This was a pilot longitudinal study conducted amongst 12 newly diagnosed head and neck cancer patients (stage III, IV, IVa, IVb) who were admitted to hospital care and were receiving chemoradiation therapy for seven weeks. Outcome variables assessed were diaphragmatic thickness and mobility, maximal inspiratory pressure (MIP) and maximum expiratory pressure (MEP) and functional capacity using six-minute walk test at baseline, three weeks and seven weeks of chemo radiation. Repeated measures ANOVA and Bonferroni post-hoc tests were used to identify significant differences at the three time points with a p &lt; 0.05. Results: Our data reported a decrease in all the variables and a significant decrease in diaphragm function during deep inspiration, respiratory pressures which indicate respiratory muscle strength and functional capacity by the end of the seventh week of chemo-radiation therapy (p &lt;0.05). Conclusion: We conclude that seven weeks of chemo-radiation therapy reduces the diaphragmatic thickness, mobility, respiratory muscle strength and functional capacity in head and neck cancer patients.

Efficacy of bright light therapy in perinatal depression: A randomized, double-blind, placebo-controlled study

BackgroundUncertainties and difficulties associated with the current treatment modalities for perinatal depression (PND) may cause some mothers to avoid treatment. Raising awareness about the effectiveness and safety of bright light therapy (BLT) may help to alleviate the challenges of PND. The main goal of this study was to evaluate the efficacy and safety of BLT versus placebo in PND. MethodA total of 30 women who were either pregnant or in first year postpartum and diagnosed with major depressive disorder were enrolled; 23 completed the study. Patients were randomly assigned to either the BLT (10,000 lux) or placebo (<500 lux) group. BLT and placebo light were applied for 45 min in the morning every day for a 3-week period. The Montgomery–Åsberg Depression Rating Scale (MADRS), Hamilton Depression Rating Scale (HAM-D), and Edinburgh Postnatal Depression Scale (EPDS) were administered weekly to evaluate response and remission rates and depression scores. ResultsThere was no significant difference between the two groups in terms of baseline depression scores. At the end of the study, the response rates assessed according to MADRS were 75% for BLT and 18.2% for placebo (p = .006), and remission rates were 41.7% vs. 0% (p = .016), respectively. There was no significant difference between the groups (p > .05) in terms of treatment-related side effects. The main limitation of this study is its small sample size, which limits the generalizability of the study's findings. ConclusionThe results indicate that BLT is more effective than placebo and is reliable in terms of side effects in PND patients. In order to expand the use of BLT in PND, new studies with larger sample sizes are needed.

The Prognostic Role of Neutrophil-to-Lymphocyte Ratio (NLR) in Testicular Germ Cell Tumor (GCT)

Highlights:Neutrophil to lymphocyte ratio (NLR) has been reported by several studies for its role as a biomarker in various diseases, however, the role of NLR in testicular GCT is still unclear.The characteristics and responses of testicular GCT patients among Indonesian men show similarity to other reports worldwide.As a parameter, NLR shows promise to be used as a potential biomarker for prognosis in testicular GCT.Abstract:The global incidence of testicular cancer is 1-2% from all cancers. The attempts to maintain high therapeutic rates while decreasing the treatment-related side effects and toxicity have become the current concern. However, the reports regarding testicular germ cell tumors (GCT) in Indonesia are limited. Thus, we aimed to evaluate the clinical characteristics of testicular GCT patients undergoing bleomycin, etoposide, and cisplatin (BEP) chemotherapy, as well as their chemotherapy response and side effects. We reported the data of patients with Testicular Germ Cell Tumor from January 2015 to December 2019. Several data were retrieved, including patient demographics, tumor characteristics, treatment, and prognosis outcome. A total of 67 patients with testicular germ cell tumors were included in this study. The mean age was 28.9 years old. The chemotherapy regimens used were four cycles of (BEP) in 36 patients (53.7%), followed by three cycles of BEP in 22 patients (32.8%). Patients with seminoma GCT mostly had a complete response (54.1%), whereas most patients with non-seminoma GCT had progressive disease (47.8%). The multiple logistic regression analysis showed that NLR and S staging were independently associated with the patient’s response to chemotherapy (OR 2.14, 95% CI 1.22, 3.78, p &lt;0.01,OR 9.43, 95% CI 1.81, 49.14, p &lt; 0.01). The clinical characteristics and response of testicular GCT patients among Indonesian men showed similarity with the current worldwide data. The NLR could be used as a potential biomarker for prognosis.

Evidence for Enhanced Efficacy of Passive Immunotherapy against Beta-Amyloid in CD33-Negative 5xFAD Mice.

Passive immunotherapy is a very promising approach for the treatment of Alzheimer’s disease (AD). Among the different antibodies under development, those targeting post-translationally modified Aβ peptides might combine efficient reduction in beta-amyloid accompanied by lower sequestration in peripheral compartments and thus anticipated and reduced treatment-related side effects. In that regard, we recently demonstrated that the antibody-mediated targeting of isoD7-modified Aβ peptides leads to the attenuation of AD-like amyloid pathology in 5xFAD mice. In order to assess novel strategies to enhance the efficacy of passive vaccination approaches, we investigated the role of CD33 for Aβ phagocytosis in transgenic mice treated with an isoD7-Aβ antibody. We crossbred 5xFAD transgenic mice with CD33 knock out (CD33KO) mice and compared the amyloid pathology in the different genotypes of the crossbreds. The knockout of CD33 in 5xFAD mice leads to a significant reduction in Aβ plaques and concomitant rescue of behavioral deficits. Passive immunotherapy of 5xFAD/CD33KO showed a significant increase in plaque-surrounding microglia compared to 5xFAD treated with the antibody. Additionally, we observed a stronger lowering of Aβ plaque load after passive immunotherapy in 5xFAD/CD33KO mice. The data suggest an additive effect of passive immunotherapy and CD33KO in terms of lowering Aβ pathology. Hence, a combination of CD33 antagonists and monoclonal antibodies might represent a strategy to enhance efficacy of passive immunotherapy in AD.

Exercise in People With Cancer: A Spotlight on Energy Regulation and Cachexia.

Exercise is increasingly becoming a standard of cancer care, with well-documented benefits for patients including improved mental wellbeing and reduced treatment-related side effects. However, important gaps in knowledge remain about how to optimise exercise prescription for people with cancer. Importantly, it remains unclear how exercise affects the progression of cancer cachexia (a wasting disease stemming from energy imbalance, and a common manifestation of advanced malignant disease), particularly once the condition has already developed. It was recently suggested that the anti-tumour effect of exercise might come from improved energetic capacity. Here, we highlight the possible effect of exercise on energetic capacity and energy regulation in the context of cancer, and how this might affect the progression of cancer cachexia. We suggest that due to the additional energy demand caused by the tumour and associated systemic inflammation, overreaching may occur more easily in people with cancer. Importantly, this could result in impaired anti-tumour immunity and/or the exacerbation of cancer cachexia. This highlights the importance of individualised exercise programs for people with cancer, with special consideration for the regulation of energy balance, ongoing monitoring and possible nutritional supplementation to support the increased energy demand caused by exercise.

Long-term outcome and safety in patients treated with immune checkpoint blockade therapies for urothelial carcinoma: Experience from real-world clinical practice.

474 Background: Anti-tumor activity and manageable safety profile of immune checkpoint blockade therapies (ICT) have been demonstrated in previous clinical trials in patients with metastatic urothelial carcinoma. To the best of our knowledge, very limited real-life data is available with the long follow-up time that confirms the durable antitumor activity and safety of ICT. In this study, we reported the real-life results of 56 months follow-up data of urothelial carcinoma patients who were treated with ICT. Methods: Metastatic urothelial carcinoma patients treated with at least one course of ICT included in the study. The primary endpoint was the overall response rate (ORR); secondary endpoints were overall survival (OS), progression-free survival (PFS), duration of the ICT treatment, and safety. Median follow-up, PFS, and OS were estimated by using the Kaplan-Meier method. Results: Data of 185 eligible patients were analyzed, 11.9% of these patients received the ICT as the first line, 76.8 % as the second line, and 11.3 % as the third or more line of treatment. The median age of the patients was 66 years, and 156 (84.3%) were male (37-86). The majority of patients (93.5%) had ECOG PS scores of 0–1 and primary tumor in the bladder was predominant (86.7%). The median follow-up time was 47(1.15-56) months. The complete response rate to ICT, partial response rate, and ORR were 10.3% (n = 19), 19.5% (n = 36), and 29.8% (n = 55), respectively. The median duration of response was 33.1 months (95% CI, 16.5–49.7). Of the fifty-five patients who responded to treatment, 28 (51%) had an ongoing response at the time of the analysis. Median PFS and OS was 3.8 (2.6–5.1) months and 8.9 (6.8–11.1) months, respectively. 56-month PFS and OS rate was 9.2% and 11.4%, respectively. 56-month PFS and OS rate for CR and PR was 56.2% and 20%, respectively. Fifty-nine percent of patients experienced a treatment-related adverse event of any grade, and 32 (17.3%) of patients had a grade 3–4 treatment-related adverse event. Because of treatment-related side effects, treatment was discontinued in 8 (4.3%) patients and adverse event that required systemic steroid use was reported in only 13 (7%) patients. Four patients (2.2%) died due to treatment-related causes. Conclusions: This 56-month analysis of real-world data confirms the durable response and long-term survival with ICT in metastatic urothelial carcinoma patients. The safety profile was consistent with prior reports, and no new safety signals emerged.