Prediction of moderate and severe toxicities of chemotherapy in older patients with cancer: a propensity weighted analysis of ELCAPA cohort.

BACKGROUND: Currently available predictive models for chemotherapy-related toxicity are not sufficiently discriminative in older patients with cancer and do not consider moderate toxicities. The purpose of this study was to identify factors associated with moderate and severe chemotherapy toxicities in older patients with cancer. MATERIALS AND METHODS: Patients aged 70+ recruited in the prospective ELCAPA cohort were analyzed. A total of 837 patients with data on toxicities had received chemotherapy without other systemic treatment and were included between 2015 and 2022. To adjust for any imbalances in the distribution of covariates between patients receiving single-agent chemotherapy vs combination chemotherapy, we applied overlap weighting (a propensity-score-based technique). We used multinomial logistic regression. RESULTS: Median (interquartile range) age was 81 (77-84). Forty-one percent experienced moderate toxicity, and 33% experienced severe toxicity. Hematologic toxicities accounted for 53% of severe toxicities and 66% of moderate toxicities. Age <80 years, cancer type, metastatic status, Eastern Cooperative Oncology Group performance status (ECOG-PS) >1, no cognitive impairment were associated with combination chemotherapy decision. In a univariate analysis with overlap weighting, no factors were associated with moderate toxicity. Hemoglobin < 0 g/dL and a CIRS-G score >12 were associated with severe toxicity. In a multivariate analysis, only hemoglobin < 10 g/dL was independently associated with severe toxicity, adjusted OR 2.96 (95% CI, 1.20-7.29). CONCLUSION: By addressing indication bias for combination chemotherapy decision, only anemia and not cancer type, combination chemotherapy was predicting for severe chemotherapy-related toxicity in older patients with cancer. We did not find any predictors of moderate chemotherapy-related toxicity.

Sarcoidosis-Like Reaction After Chemotherapy Mimicking Metastasis in a Patient With Two Synchronous Tumors: A Case Report.

Sarcoidosis presents a diagnostic challenge due to its diverse clinical manifestations and potential to mimic malignancies. We report a clinical case involving a 46-year-old woman diagnosed with localized synchronous ovarian and endometrial carcinomas treated with surgery. Following adjuvant chemotherapy and radiotherapy, the patient developed suspicious pulmonary micronodules and lymphadenopathy observed in imaging studies, raising concerns about cancer recurrence. Histopathological analysis revealed chronic granulomatous inflammation without evidence of malignancy, leading to a diagnosis of a sarcoidosis-like reaction secondary to chemotherapy. Remarkably, these lesions resolved spontaneously without specific intervention. This case emphasizes the importance of a multidisciplinary approach in managing complex oncological presentations and underscores the significance of histopathological examination in distinguishing between malignancy and chemotherapy-induced sarcoidosis-like reactions.

Association of sarcopenia with severe chemotherapy toxicities and survival in patients with advanced gastric cancer.

BACKGROUND: Sarcopenia or skeletal muscle depletion is a poor prognostic factor for gastric cancer (GC). However, existing cutoff values of skeletal muscle index (SMI) for defining sarcopenia have been found to have limitations when clinically applied. This study aimed to determine the optimal cutoff for SMI to predict severe toxicities of chemotherapy and overall survival (OS) in patients with advanced GC. METHODS: Patients with metastatic gastric adenocarcinoma who received first-line palliative chemotherapy between January 2014 and December 2021 at Queen Mary Hospital, Hong Kong, were included in this study. The SMI was determined via a pre-chemotherapy computed tomography scan. Optimal cutoff points of SMI were identified by recursive partitioning analysis. Univariate and multivariate analyses evaluating risk factors of severe chemotherapy toxicities and OS were also performed. RESULTS: A total of 158 patients (male: 108 (68.4%), median age: 65.3) were included. The SMI cutoff to define low SMI was ≤33 cm2/m2 for males and ≤28 cm2/m2 for females; 30 patients (19.0%) had low SMI. Patients with low SMI had a higher incidence of hematological toxicities (63.3% vs 32.0%, P = .001) and non-hematological toxicities (66.7% vs 36.7%, P = .003). Multivariable analysis indicated that low SMI and low serum albumin (≤28 g/L) were independent predictive factors of hematological toxicity, while low SMI and neutrophil-lymphocyte ratio ≥5 were predictive factors of non-hematological toxicity. Moreover, patients with low SMI had a significantly shorter OS (P = .011), lower response rate to chemotherapy (P = .045), and lower utilization of subsequent lines of treatment (P < .001). CONCLUSIONS: Using pre-chemotherapy SMI cutoff (≤33 cm2/m2 for males and 28 cm2/m2 for females) one can identify individuals with a higher risk of severe chemotherapy toxicities and worse prognosis.

Exploring the High-Grade and Refractory Neurotoxicity of Teclistamab: An Underreported Entity.

T-cell re-directing bispecific antibodies targeting B-cell maturation antigens have recently entered real-world use in relapsed/refractory multiple myeloma. While no head-to-head comparison has been done, they have generally been observed to have lower-grade toxicities compared with their chimeric antigen receptor T-cell (CAR-T) counterparts. However, in our real-world, single-institution experience, we have encountered two patients receiving teclistamab who experienced high-grade and refractory immune effector cell-associated neurotoxicity syndrome (ICANS) that did not respond to traditional toxicity mitigation strategies of high-dose corticosteroids or other immunosuppressive therapies. As we increase our use of these novel and vital agents, caution must be warranted.

Biobehavioral Influences of Stress and Inflammation on Mucositis in Adolescents and Young Adults with Cancer: Results from a Pilot Study.

Purpose: Chemotherapy-induced mucositis is a prevalent and burdensome toxicity among adolescent and young adults (AYAs) with cancer and impedes the delivery of optimal therapy. Its development is not well understood, but baseline stress and inflammation may be contributory factors. This pilot study evaluates stress and inflammation as risk factors for mucositis, identifies effect size estimates, and evaluates the feasibility of a prospective study to investigate mucositis development. Methods: Thirty AYAs receiving chemotherapy with substantial risk of mucositis completed baseline stress measures, and serum was collected for inflammatory biomarker analysis. Regression and mediation analyses determined the relationship between stress/inflammation and mucositis. Results: Stress appears to be a significant risk factor for incidence of mucositis (odds ratio 1.13, p = 0.125) and predicts total mucositis score (ß = 0.281, p = 0.023) as well as peak incidence (ß = 0.052, p = 0.018). Baseline levels of interleukin (IL)-1a and epidermal growth factor (EGF) predicted mucositis development, and EGF and IL-8 may mediate the relationship between stress and mucositis. Findings suggest that stress-induced inflammation exacerbates symptom development. Conclusion: Results from this pilot study inform mucositis symptom models, suggesting that psychosocial and physiologic factors are involved in development. Importantly, this pilot study provides initial effect size estimates, including magnitude and direction of relationships, that are essential to informing larger, more robustly powered studies. High enrollment, low attrition, and minimal missing data in this study suggest this model is feasible for research in this population. Importantly, this work is a first step in identifying new risk factors for mucositis and targets for nurse-led interventions to prevent toxicity development.

Paclitaxel-Induced Cutaneous Lupus Erythematosus and Raynaud's Phenomenon.

Taxanes, in combination with platinum-based drugs, are considered the initial treatment option for certain types of cancer, including ovarian cancer. Here, we report the case of a 59-year-old woman who developed a malar rash on her face, a maculopapular rash on her forearms, and bluish discoloration on her fingers immediately following the end of the third cycle of chemotherapy. After discontinuing paclitaxel and using oral and topical steroids for rash and diltiazem and topical minoxidil for the treatment of Raynaud's phenomenon, the symptoms completely resolved. While taxanes are known to cause drug-induced lupus, there has never been any information on taxanes causing isolated Raynaud's phenomenon. This is the first case report that suggests paclitaxel-induced Raynaud's phenomenon along with paclitaxel-induced lupus.

A Retrospective Analysis of Metronomic Cyclophosphamide, Methotrexate, and Fluorouracil (CMF) Versus Docetaxel and Cyclophosphamide (TC) as Adjuvant Treatment in Early Stage, Hormone Receptor Positive, HER2 Negative Breast Cancer.

BACKGROUND: Anthracycline and taxane-based doublets have largely replaced cyclophosphamide, methotrexate, and fluorouracil (CMF) as preferred regimens in the adjuvant treatment of breast cancer. Metronomic CMF is associated with improved tolerability over anthracycline or taxane-based regimens. Previously, there have been no direct comparisons between taxane-based regimens and CMF. MATERIALS AND METHODS: We performed a retrospective review of 98 breast cancer patients treated at the Seattle Cancer Care Alliance from February 2015 through December 2018 that received either metronomic CMF or docetaxel and cyclophosphamide (TC) as adjuvant therapy for early-stage, hormone receptor-positive/human epidermal growth factor receptor-2 negative (HR+/HER2-) breast cancer. The primary outcome assessed was disease-free survival (DFS). Secondary outcomes included overall survival (OS), dose intensity, and adverse effects. RESULTS: With an average follow-up of 35.9 and 28.2 months for CMF and TC, respectively, there was no significant difference in DFS or OS between the chemotherapy regimens. DFS at 3 years was 96.7% vs. 94.3% and OS 96.7% vs. 100% for CMF and TC, respectively. There were more dose delays in the CMF group, but on average, patients receiving either regimen achieved a dose intensity ≥85%. There was a trend towards increased hospitalization or emergency department utilization (23.1% vs. 10.6%) and Grade 4 toxicities (9.6% vs. 4.3%) with TC vs. CMF. CONCLUSION: Metronomic CMF offers equivalent survival outcomes to TC and remains a viable option in the adjuvant treatment of HR+/HER2- breast cancer. There was a trend towards increased Grade 4 toxicities and hospitalizations with TC, suggesting that metronomic CMF may offer a more tolerable treatment option while maintaining excellent disease outcomes.

Retinoblastoma management in 13q deletion syndrome patients using super-selective chemotherapies and other cancer-directed interventions.

BACKGROUND: This study aimed to identify best practices for treating 13q deletion syndrome (13q-) patients with retinoblastoma in the era of super-selective ophthalmic artery chemosurgery (OAC) and intravitreal injection therapy (IVIT). METHODS: Retrospective study of 21 eyes from 14 patients with retinoblastoma and 13q- who were treated at Memorial Sloan Kettering Cancer Center (MSKCC) between May 2006 and May 2020, with a mean follow up of 3.7 years. Ocular survival, patient survival, and treatment toxicities were assessed. RESULTS: Nine of the 12 eyes that underwent OAC/IVIT at MSKCC have been progression free for at least 1 year since their last treatments. Fifteen out of 26 OAC cycles resulted in grade 3-4 hematologic toxicity. There was one death from sepsis in the setting of intravenous chemotherapy (IVC) for metastatic disease that occurred after OAC/IVIT therapy. The 2-year Kaplan-Meier ocular survival estimate for the whole cohort was 75% and for the eyes that received OAC or IVIT at MSKCC 83%. For OAC hematologic toxicities, one platelet transfusion and two filgrastim doses were administered, and one patient was hospitalized for neutropenic fevers. CONCLUSIONS: The majority of 13q- eyes treated with OAC/IVIT-based regimens can be cured, and there were no deaths related to complications from OAC or IVIT. 13q- Patients did have increased risk of systemic treatment complications, even from super-selective chemotherapies. Despite these toxicities, only one patient developed febrile neutropenia, one patient required a blood product transfusion, and two patients received filgrastim for both OAC and IVC complications. PRÉCIS: Children with 13q deletion syndrome with retinoblastoma managed with intra-arterial and intravitreal chemotherapy have excellent patient and ocular survival with acceptable toxicity.

Therapeutic Characteristics, Chemotherapy-Related Toxicities and Survivorship in Colorectal Cancer Patients.

BACKGROUND: Colorectal Cancer (CRC) is a major health problem around the globe. In Morocco, the disease ranks third after breast and lung cancers. This study is the first in Morocco to investigate epidemiological, clinical and therapeutic features while exhaustively describing toxic side-effects to chemotherapy of CRC and studying the 3-years survivorship. METHODS: This is a descriptive and analytical retrospective study of about 290 patients with CRC enrolled during the period of January-December 2013. Statistical analysis was performed to correlate clinicopathological data with chemotherapy toxicity and survivorship in patients, by Chi2 test. Overall Survival (OS) rate has been calculated by the Kaplan-Meier method and compared using Log-rank test. RESULTS: Fifty-five percent had a tumor localized in rectum, and 42,8% in colon. Mean age of these patients at diagnosis was 56,16 ± 14,6. incidence rate of adverse events (grade I to IV) was 85,6%. Diarrhea was the predominant toxicity (4.6%) occurring at a high grade (grade III-IV).The 3-years OS rate of patients with CRC was 71%. OS decreased by age, and patients with age subgroup between 40 to 59 years had a better OS than the other age subgroups (60 to 79 years and >80 years) with a p-value of 0.0001. Occurence of toxicity (all grades and types) was linked to a higher survival rates compared to the group who had no toxicity noticed (p-value of 0.001). CONCLUSION: Our study shows that patients who had a polychemotherapy had a better OS than those who had monotherapy (p-value of 0.002).

Oxaliplatin-induced neuropathy: the preventive effect of a new super-oxide dismutase modulator.

By using the differential in level of oxidative status between normal and cancer cells, SuperOxide Dismutase (SOD) mimetics can have anti-tumor efficacy and prevent oxaliplatin-induced peripheral neuropathy. Our objective was to evaluate the neuroprotective efficacy of MAG, a new SOD mimic. In vitro, the effects of MAG alone or with oxaliplatin were studied on colon cancer cells (HT29 and CT26) and on normal fibroblast cells (NIH3T3). The cell viability (by crystal violet) as well as the production of reactive forms of oxygen and glutathione (by spectrofluorimetric assay) was measured. In vivo, efficacy on tumor growth was assessed in mice grafted with CT26 colon cancer cells. The effects on induced neurotoxicity were measured by specific behavioral Von Frey nociception, cold-plate tests, specific functional neuromuscular assay and electron microscopy. In vitro, MAG induced a production of hydrogen peroxide in all cells. At 24 h-incubation, MAG exhibits a cytotoxic activity in all cell lines. A cytotoxic additive effect of MAG and oxaliplatin was observed through oxidative burst. In vivo, oxaliplatin-treated mice associated with MAG did not counteract oxaliplatin's antitumoral efficacy. After 4 weeks of treatment with oxaliplatin combined with MAG, behavioral and functional tests showed a decrease in peripheral neuropathy induced by oxaliplatin in vivo. Electron microscopy analyses on sciatic nerves revealed an oxaliplatin-induced demyelination which is prevented by the association of MAG to this chemotherapy. In conclusion, MAG prevents the appearance of sensitive axonal neuropathy and neuromuscular disorders induced by oxaliplatin without affecting its antitumor activity.

An imaging-based review of systemic therapies and associated toxicities in metastatic pancreatic cancer as per the 2018 ASCO guidelines: what every radiologist should know.

OBJECTIVE: To provide an overview of what radiologists should know about systemic agents utilized in the modern treatment of metastatic pancreatic cancer and their associated toxicities. RESULTS: The clinical landscape of metastatic pancreatic cancer has significantly evolved in recent years, with the advent of new first- and second-line systemic therapies. As these systemic treatment options continue to expand, knowledge of their clinically relevant features is becoming critical for radiologists. While the issues of surgical resectability and tumor response evaluation of advanced stages of pancreatic cancer have been thoroughly discussed in the radiology literature, the diagnostic importance of systemic therapies has tended to be less well appreciated. In this review, we provide a primer for radiologists outlining the radiologically pertinent features of modern systemic therapies used in the treatment of metastatic pancreatic ductal adenocarcinoma. These systemic agents are discussed from the standpoint of the newly updated 2018 ( https://doi.org/10.1007/s00261-019-01954-z ) guidelines for the treatment of metastatic pancreatic cancer from the American Society of Clinical Oncology (ASCO). Understanding the radiology relevance of these modern therapeutic agents is critical, especially with regard to treatment response and toxicity assessment. CONCLUSION: Knowledge of the modern systemic therapies utilized in the treatment of metastatic pancreatic cancer and their associated toxicity profiles is critical in diagnostic imaging interpretation.

Hospitalisations and emergency department visits in cancer patients receiving systemic therapy: Systematic review and meta-analysis.

Emergency department visits and hospitalisations (ED+H) during systemic therapy are undesirable for both patients and the health system. We undertook a systematic literature review and meta-analysis to evaluate the frequency of unplanned all-cause and treatment-related ED+H among adults receiving adjuvant or palliative-intent systemic therapy for all cancers. Randomised controlled trials (RCT) and observational studies (OS) reporting ED+H were identified from Medline and EMBASE from inception to June 2016. Quality was assessed using modified STROBE, CONSORT or PRISMA guidelines, depending on study type. A total of 112 OS (308,662 patients) and 26 RCTs (16,081 patients) met inclusion criteria. Most articles focused on palliative treatment (59%) delivered as first-line, in breast, lung and colorectal cancers. Only 20 articles reported ED frequency. Treatment-related and all-cause hospitalisations were more common in routine practice than in RCTs (29% vs. 16% and 42% vs. 28% respectively); frequency varied by treatment intent and tumour site. Methodological issues were common, particularly poor definition of the at-risk period. Hospitalisations are common, especially in unselected populations, but few articles report this and do so poorly. Routine, standardised reporting of ED+H during chemotherapy should be included in RCT reports and evaluated in routine care following adoption of new treatments.

[Impact of cancer muscle mass loss on anticancer treatment toxicities]. / Conséquences de la diminution de la masse musculaire sur la tolérance des traitements anticancéreux.

Administration of targeted therapies as a flat dose and administration of chemotherapy based on body surface area do not take into account several important sources of inter-individual variation. These variations could be responsible partially for the occurrence of toxicity. Furthermore, the availability of high-resolution CT images in the record of cancer patients, from which key body composition information may be derived, allows us to study the relationship between body composition and toxicity. If many studies have highlighted this relationship, the mechanisms are not completely understood. There are some arguments for a pharmacokinetic hypothesis: low muscle mass i.e. sarcopenia, is associated with high drug plasma concentration which in turn is associated with an increase in the incidence of toxicity. The other hypothesis is that sarcopenic patients have a higher susceptibility to medical events leading to an increase in chemotherapy toxicity. This concept of frailty was widely described in studies in the elderly. This body composition analysis opened a huge area of research and many questions still need to be resolved. Defining the cut-offs values for low muscle mass is important since in most of the studies, the cut-offs values used were defined using survival studies. What could be the physiological link between cut-off values defined by survival studies and chemotherapy toxicities? Authors also used the median values, the level which predicted the occurrence of toxicity most accurately and sometimes the measure of the psoas. The final and crucial question is the capacity of reducing toxicity by body composition based dosing.

Pharmacokinetics of high-dose methotrexate in infants aged less than 12 months treated for aggressive brain tumors.

PURPOSE: In infants aged less than 12 months, there are few data on pharmacokinetics of high-dose methotrexate (MTX) for brain tumors at the dose of 8 g/m(2). Consolidated knowledges are present only with the dose of 5 g/m(2) in acute lymphoblastic leukemia. METHODS: We collected data on 8 infants at the time of their first treatment with high-dose MTX, 8 g/m(2), to evaluate the pharmacokinetic profile. All children had a dose adjustment with a weight-based prescription (1 m(2) = 30 kg). RESULTS: The median age was 4.5 months (range 0-9). The median weight was 5.63 kg (range 3.12-9.0). The median steady-state MTX concentration at the end of 6-hr infusion was 486 µM/L (range 227-790). The median systemic MTX clearance was 4.14 L/h/m(2) (range 1.98-9.35). The median MTX concentration after 24 h from the beginning of infusion was 3.29 µM/L (range 1.14-100.44). Three (37.5 %) patients had a delayed elimination of MTX (delayed early, delayed late, or total delayed: one for each). These altered elimination occurred principally in children weighing less than 4 kg (p: 0.0179). Moreover, a systemic MTX clearance at the end of infusion minor than 3 L/h/m(2) can predict a delayed elimination (p: 0.0179). Patients with altered elimination underwent rescue measures (leucovorin supplement and/or exchange transfusion). CONCLUSIONS: Our data suggest that a higher dose of MTX for the treatment of aggressive brain tumors in early infants had an acceptable pharmacokinetic profile. Greater attention must be used in the treatment of children weighing less than 4 kg.

Comparison of toxicity profile and tolerability between two standard of care paclitaxel-based adjuvant chemotherapy regimens in breast cancer.

In breast cancer, there are two widely used paclitaxel-based adjuvant chemotherapies, either dose dense paclitaxel (ddP) or weekly paclitaxel (wP). To our knowledge, the comparisons of toxicity and tolerability between the two regimens have never been reported in the literature. This is a retrospective single-institution charts review of breast cancer patients who were treated with paclitaxel-based chemotherapy either ddP or wP. In total, 76 and 45 patients with breast cancer received adjuvant standard ddP and wP, respectively. Patient characteristics in both groups were comparable. Our results showed no statistical significant difference in toxicity profile and tolerability between the two regimens. Particularly, chemotherapy-induced peripheral neuropathy (CIPN) was equally observed in both schedules. Furthermore, grade 3 and 4 CIPN was observed in 17 and 18 %, respectively (p = 0.93). In terms of tolerability, both regimens resulted in similar rates of hospitalization and treatment discontinuation. Our data analysis indicates no significant difference in toxicity profile between the two standard paclitaxel regimens in breast cancer. However, this is a small sample-sized retrospective study and further prospective trial with a larger sample size is warranted.