The treatment landscape of gynecologic cancers has expanded in recent years to include targeted and immune-based therapies. These therapies often have ocular side effects not seen with conventional chemotherapies, some of which can cause significant visual impairment if not recognized in a timely fashion. Clinicians must know how to appropriately identify, mitigate, and treat these ocular adverse events. Management often involves working with an interdisciplinary team of eye specialists, and it is important to know when to refer patients for specialized care. Proactive identification of eye specialists, especially in rural and community settings where access to care can be limited, may be necessary. Here, we discuss the management of common ocular toxicities seen with novel anticancer agents used to treat gynecologic cancers.

BACKGROUND: Breast cancer treatment is multimodal, but not all patients benefit from each treatment, and many experience morbidities significantly impacting quality of life. There is increasing interest in tailoring breast cancer treatments to optimize oncological outcomes and reduce treatment burden, but it is vital that future trials focus on treatments that most impact patients. This study was designed to explore patient experiences of treatment to inform future research.
METHODS: An online survey was co-developed with patient advocates to explore respondents\' experiences of breast cancer treatment. Questions included simple demographics, treatments received, and views regarding omitting treatments if that is deemed safe. The survey was circulated via social media and patient advocacy groups. Responses were summarized by using simple statistics; free text was analyzed thematically.
RESULTS: Of the 235 participants completing the survey, 194 (82.6%) would choose to omit a specific treatment if safe to do so. The most commonly selected treatments were chemotherapy (n = 69, 35.6%) and endocrine therapy (n = 61, 31.4%) mainly due to side effects. Fewer respondents would choose to omit surgery (n = 40, 20.6%) or radiotherapy (n = 20, 10.3%). Several women commented that survival was their \"absolute priority\" and that high-quality evidence to support the safety of reducing treatment would be essential.
CONCLUSIONS: Patients with breast cancer are individuals who may wish to optimize different components of their treatment. A portfolio of studies co-designed with patients is needed to establish an evidence base for greater treatment personalization with studies focused on reducing avoidable chemotherapy and endocrine therapy a priority.

BACKGROUND: Adjuvant treatment with immune checkpoint inhibitors, such as PD1-antibodies (ICI) ± CTLA4-antibodies (cICI) or targeted therapy with BRAF/MEK inhibitors (TT), has shown a significant improvement in disease-free survival (DFS) for high-risk melanoma patients. However, due to specific side effects, the choice of treatment is often influenced by the risk of toxicity. Therefore, the role of physicians in treatment decisions of patients is crucial. This study investigated for the first time in a multicenter setting the attitudes and preferences of dermatooncologists in Germany and Switzerland regarding adjuvant treatment with (c)ICI and TT.
METHODS: In the GERMELATOX-A study, 108 physicians (median age: 32 yrs, 67.6% female) from 11 skin cancer centers were surveyed to rate typical side effect scenarios of (c)ICI and TT treatments and then compared to patients\' ratings evaluated in a previous analysis from the same centers. The scenarios described mild-to-moderate or severe toxicity and included melanoma relapse leading to death. The physicians were asked about the level of side effects they would tolerate in exchange for a reduction in melanoma relapse and an increase in survival at 5 years.
RESULTS: The preferences of physicians and patients revealed significant differences regarding adjuvant melanoma treatment with (c)ICI and TT (p < 0.05). Compared to patients, physicians tend to value a melanoma relapse less severe, according to a visual analog scale. They were also less threatened by all scenarios of side effects during adjuvant treatment with (c)ICI or TT, compared to patients. Physicians required lower risk reductions for disease-free survival (DFS) and overall survival (OS) for both ICI and TT and their drug-related side effects to accept these treatments. In case of severe side effects, physicians required similar 5-year DFS rates for ICI and TT (60-65%), while patients needed a 15% improvement of 5-year DFS for ICI compared to TT (80%/65%). For survival, physicians expected an OS improvement of + 10% for all three treatment modalities, whereas patients required a higher increase: + 18-22% for ICI and + 15% for TT.
CONCLUSIONS: Our study highlights the importance of understanding the patient\'s perspective and a potential difference to the doctor\'s view when making decisions about adjuvant melanoma treatment with (c)ICI and TT, especially as these treatments are increasingly being implemented in earlier stages.

UNASSIGNED: Tumor lysis syndrome (TLS) often occurs early after induction chemotherapy for acute lymphoblastic leukemia (ALL) and can rapidly progress. This study aimed to construct a machine learning model to predict the risk of TLS using clinical indicators at the time of ALL diagnosis.
UNASSIGNED: This observational cohort study was conducted at the National Clinical Research Center for Child Health and Disease. Data were collected from pediatric ALL patients diagnosed between December 2008 and December 2021. Four machine learning models were constructed using the Least Absolute Shrinkage and Selection Operator (LASSO) to select key clinical indicators for model construction.
UNASSIGNED: The study included 2,243 pediatric ALL patients, and the occurrence of TLS was 8.87%. A total of 33 indicators with missing values ≤30% were collected, and 12 risk factors were selected through LASSO regression analysis. The CatBoost model with the best performance after feature screening was selected to predict the TLS of ALL patients. The CatBoost model had an AUC of 0.832 and an accuracy of 0.758. The risk factors most associated with TLS were the absence of potassium, phosphorus, aspartate transaminase (AST), white blood cell count (WBC), and urea levels.
UNASSIGNED: We developed the first TLS prediction model for pediatric ALL to assist clinicians in risk stratification at diagnosis and in developing personalized treatment protocols. This study is registered on the China Clinical Trials Registry platform (ChiCTR2200060616).
UNASSIGNED: https://www.chictr.org.cn/, identifier ChiCTR2200060616.

BACKGROUND: Delays in diagnosis and initiation of treatment have a negative impact on the prognosis and survival of head and neck cancer (HNC) patients. These delays also involve more intensive treatments with greater toxicity, dysfunction, and morbidity.
METHODS: This was a retrospective observational study with patients diagnosed with HNC between January 1, 2018, and December 31, 2021. The main objective was to estimate whether the time to diagnosis (TD) and time until treatment initiation (TIT) translated into changes in the patient\'s overall survival (OS). Multivariate data analysis was performed with the Cox regression model. Significance was considered for p<0.05.
RESULTS: A total of 139 patients were included in this study. Median TD was 126 days and median TIT was 43 days. No association between TD, TIT, treatment toxicity, and OS was found. Being a smoker was associated with a longer TD (p=0.05, hazard ratios {HR}=1.01). TIT was significantly shorter in higher grades (p=0.03, HR=0.57) and during coronavirus disease 2019 (COVID-19) (p=0.04, HR=0.57), but higher in larger disease (tumor {T}) (p=0.04, HR=1.39). A higher T (p=0.01, HR=2.67) and lymph node metastasis (nodes {N}) (p=0.02, HR=2.24) were identified as risk factors with a negative impact on OS, whereas grade was positively correlated (p=0.05, HR=0.32).
CONCLUSIONS: Even though there was no correlation between TD and TIT, and OS, action still needs to be taken to shorten these times. T and N remain negative predictive prognostic markers of HNC.

As most patients with metastatic urothelial carcinoma (mUC) will be treated with immune checkpoint inhibitors (ICI), familiarity with their associated immune-related adverse events (irAEs) is critical. We describe the characteristics and outcomes of ICI-treated mUC patients who experienced irAEs requiring treatment interruption (TI) or permanent discontinuation.
ICI-treated mUC patients who developed grade ≥2 irAEs were reviewed. Clinical-, treatment-, and toxicity-related data were evaluated. Toxicity was graded per common terminology for categorization of adverse events v5.0. Cohorts were divided into patients who underwent ICI rechallenge and those who required permanent ICI discontinuation. Time to treatment interruption (TTI), time to next treatment, and duration of clinical benefit were assessed descriptively. Progression-free survival and overall survival (OS) were estimated using Kaplan-Meier methodology.
Of 200 ICI-treated mUC patients at Cleveland Clinic between October 2015 and October 2020, 16 (8%) experienced ≥ grade 2 irAEs necessitating TI. Median TTI among all patients was 6.5 months (range, 1-19). Eleven patients (69%) required corticosteroids. ICI were held and rechallenged in 10 patients (62%) and permanently discontinued in 6 patients (38%). Of the 10 ICI-rechallenged patients, 7 (70%) experienced another irAE upon rechallenge with median time to irAE recurrence of 2.9 months (range, 0.1-10.9); 3 (30%) eventually discontinued ICI due to recrudescent irAEs. Four (40%) of the 10 ICI-rechallenged patients received subsequent therapy. Five (83%) of the 6 patients who permanently discontinued ICI demonstrated durable clinical benefit off therapy with median duration of clinical benefit 17.7 months (range, 14.2-55.2). Two-year OS was 40% (95% CI: 19%-86%) in the ICI rechallenge cohort and 67% (95% CI: 38%-100%) in the permanent discontinuation cohort.
ICI-treated mUC patients who developed irAEs requiring TI had a high rate of subsequent irAEs upon ICI rechallenge. Importantly, patients who permanently discontinued ICI due to irAE demonstrated durable clinical benefit off treatment.

The present study compares two groups of locally advanced patients with head and neck squamous cell carcinoma (LA-HNSCC) undergoing concurrent chemoradiotherapy (cCHRT), specifically those for whom it is a first-line treatment and those who have previously received induction chemotherapy (iCHT). The crucial question is whether iCHT is a serious burden during subsequent treatment for LA-HNSCC and how iCHT affects the tolerance to cCHRT. Of the 107 LA-HNSCC patients, 54 received cisplatin-based iCHT prior to cCHRT. The patients were clinically monitored at weekly intervals from the day before until the completion of the cCHRT. The 843 blood samples were collected and divided into two aliquots: for laboratory blood tests and for nuclear magnetic resonance (NMR) spectroscopy (a Bruker 400 MHz spectrometer). The NMR metabolites and the clinical parameters from the laboratory blood tests were analyzed using orthogonal partial least squares analysis (OPLS) and the Mann-Whitney U test (MWU). After iCHT, the patients begin cCHRT with significantly (MWU p-value < 0.05) elevated blood serum lipids, betaine, glycine, phosphocholine, and reticulocyte count, as well as significantly lowered NMR inflammatory markers, serine, hematocrit, neutrophile, monocyte, red blood cells, hemoglobin, and CRP. During cCHRT, a significant increase in albumin and psychological distress was observed, as well as a significant decrease in platelet, N-acetyl-cysteine, tyrosine, and phenylalanine, in patients who received iCHT. Importantly, all clinical symptoms (except the decreased platelets) and most metabolic alterations (except for betaine, serine, tyrosine, glucose, and phosphocholine) resolve until the completion of cCHRT. In conclusion, iCHT results in hematological toxicity, altered lipids, and one-carbon metabolism, as well as downregulated inflammation, as observed at the beginning and during cCHRT. However, these complications are temporary, and most of them resolve at the end of the treatment. This suggests that iCHT prior to cCHRT does not pose a significant burden and should be considered as a safe treatment option for LA-HNSCC.

Physical activity may be associated with cancer treatment toxicity, but generalizability to geriatric oncology is unclear. As many older adults have low levels of physical activity and technology use, this area needs further exploration. We evaluated the feasibility of daily step count monitoring and the association between step counts and treatment-emergent symptoms.
Adults aged 65+ starting treatment (chemotherapy, enzalutamide/abiraterone, or radium-223) for metastatic prostate cancer were enrolled in a prospective cohort study. Participants reported step counts (measured via smartphone) and symptoms (Edmonton Symptom Assessment Scale) daily for one treatment cycle (i.e., 3-4 weeks). Embedded semi-structured interviews were performed upon completion of the study. The feasibility of daily monitoring was evaluated with descriptive statistics and thematic analysis. The predictive validity of a decline in daily steps (compared to pre-treatment baseline) for the emergence of symptoms was examined using sensitivity and positive predictive value (PPV). Associations between a 15% decline in steps and the emergence of moderate (4-6/10) to severe (7-10/10) symptoms and pain in the next 24 h were assessed using logistic regression.
Of 90 participants, 47 engaged in step count monitoring (median age = 75, range = 65-88; 52.2% participation rate). Daily physical activity monitoring was found to be feasible (94% retention rate; 90.5% median response rate) with multiple patient-reported benefits including increased self-awareness and motivation to engage in physical activity. During the first treatment cycle, instances of a 15% decline in steps were common (n = 37, 78.7%), as was the emergence of moderate to severe symptoms overall (n = 40, 85.1%) and pain (n = 26, 55.3%). The predictive validity of a 15% decline in steps on the emergence of moderate to severe symptoms was good (sensitivity = 81.8%, 95% confidence interval [CI] = 68.7-95.0; PPV = 73.0%, 95% CI = 58.7-87.3), although the PPV for pain was poor (sensitivity = 77.8%, 95% CI = 58.6-97.0; PPV = 37.8%, 95% CI = 22.2-53.5). In the regression models, changes in daily physical activity were not associated with symptoms or pain.
Changes in physical activity had modest ability to predict moderate to severe symptoms overall. Although participation was suboptimal, daily activity monitoring in older adults with cancer appears feasible and may have other uses such as improving physical activity levels. Further studies are warranted.

OBJECTIVE: Adjuvant treatment with immune checkpoint inhibitors like PD1-antibodies (ICI) ± CTLA4-antibodies (cICI) or targeted therapy with BRAF/MEK inhibitors (TT) in high-risk melanoma patients demonstrate a significant improvement in disease-free survival (DFS). Due to specific side effects, the choice of treatment is very often driven by the risk for toxicity. This study addressed for the first time in a multicenter setting the attitudes and preferences of melanoma patients for adjuvant treatment with (c)ICI and TT.
METHODS: In this study (\"GERMELATOX-A\"), 136 low-risk melanoma patients from 11 skin cancer centers were asked to rate side effect scenarios typical for each (c)ICI and TT with mild-to-moderate or severe toxicity and melanoma recurrence leading to cancer death. We asked patients about the reduction in melanoma relapse and the survival increase at 5 years they would require to tolerate defined side-effects.
RESULTS: By VAS, patients on average valued melanoma relapse worse than all scenarios of side-effects during treatment with (c)ICI or TT. In case of severe side effects, patients required a 15% higher rate of DFS at 5 years for (c)ICI (80%) compared to TT (65%). For survival, patients required an increase of 5-10% for melanoma survival during (c)ICI (85%/80%) compared to TT (75%).
CONCLUSIONS: Our study demonstrated a pronounced variation of patient preferences for toxicity and outcomes and a clear preference for TT. As adjuvant melanoma treatment with (c)ICI and TT will be increasingly implemented in earlier stages, precise knowledge of the patient perspective can be helpful for decision making.

OBJECTIVE: Patients with multiple myeloma (MM) enrolled in randomized control trials (RCTs) discontinue treatment for various reasons; however, no prior study has analyzed reasons for discontinuation. We performed a systematic review of MM RCTs to investigate reasons for treatment discontinuation, imbalances between trial cohorts, and reporting practices.
METHODS: A comprehensive search for RCTs in MM from 2015 to 2021 identified 45 studies meeting inclusion criteria.
RESULTS: Of 21 236 randomized patients, 10 161 (47.8%) discontinued therapy by primary endpoint ascertainment. Causes of discontinuation included progression (n = 4790; 22.6% of randomized patients); toxicity (n = 2569; 12.1%); patient/physician withdrawal (n = 1200; 5.7%) and death (n = 495; 2.3%). Of randomized patients, 20 914 (98.5%) were included in the RCT analysis. Imbalances of attrition, defined as trials with greater than 5% absolute difference in discontinuation rate for reasons other than death, progression, and toxicity between intervention and control arms, were found in 11 (24.4%) studies.
CONCLUSIONS: Although progression is the most common reason for RCT treatment discontinuation in patients with MM, over 10% discontinued due to toxicity. Furthermore, 24.4% of trials showed substantial imbalances between trial cohorts; raising concern for informative censoring and emphasizes the importance of detailed characterization of withdrawal in MM RCTs.