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Background Early studies showed promise of combined anti-epidermal growth factor receptor (EGFR) plus anti–vascular endothelial growth factor (VEGF) antibodies for advanced colorectal cancer (CRC), yet this was later rejected as toxic and ineffective in studies not selected for RAS status. We studied advanced KRAS wild-type CRC, as second-line treatment, using irinotecan-cetuximab with or without the anti-VEGF receptor antibody ramucirumab. Methods Patients with 1 prior regimen including fluoropyrimidine, oxaliplatin, and bevacizumab, with KRAS wild-type tumors were stratified by Eastern Cooperative Oncology Group Performance Score, time since last chemotherapy, and progression on oxaliplatin to irinotecan-cetuximab (IC) (180 mg/m2 and 500 mg/m2 every 2 weeks) vs modified ICR (irinotecan-cetuximab with ramucirumab 150 mg/m2 and 400 mg/m2 plus 6 mg/kg, respectively). A total of 102 patients were compared for progression-free survival (PFS) as primary endpoint (85% power for 70% improvement in median PFS from 4.5 to 7.65 months). Results Of the 102 enrolled, 44 treated with irinotecan-cetuximab and 45 with modified ramucirumab were evaluable. Median PFS was 6.0 months vs 9.2 months, respectively (hazard ratio = 0.75, P = .07; statistically significant by study design for P  < .128). Response rate was 23% vs 36% (P = .27), and disease-control rate was 52% vs 73% (P  = .05). Grade 3 or higher toxicity was equivalent. Overall survival was not significantly different at approximately 19 months. Conclusion Previous phase 3 trials without RAS genotyping rejected combining anti-epidermal growth factor receptor and anti-VEGF drugs. In this randomized multicenter phase 2 study for KRAS wild-type CRC (all previously bevacizumab treated), the addition of ramucirumab to irinotecan and cetuximab improved PFS and disease control rate, showing the combination is feasible and effective. Further, phase 3 trials with appropriate patient-selection are required. (NCT01079780) [ABSTRACT FROM AUTHOR]

Background The association of body composition with epithelial ovarian carcinoma (EOC) mortality is poorly understood. To date, evidence suggests that high adiposity is associated with decreased mortality (an obesity paradox), but the impact of muscle on this association has not been investigated. Herein, we define associations of muscle and adiposity joint-exposure body composition phenotypes with EOC mortality. Methods Body composition from 500 women in the Body Composition and Epithelial Ovarian Cancer Survival Study was dichotomized as normal or low skeletal muscle index (SMI), a proxy for sarcopenia, and high or low adiposity. Four phenotypes were classified as fit (normal SMI and low adiposity; reference; 16.2%), overweight or obese (normal SMI and high adiposity; 51.2%), sarcopenia and overweight or obese (low SMI and high adiposity; 15.6%), and sarcopenia or cachexia (low SMI and low adiposity; 17%). We used multivariable Cox models to estimate associations of each phenotype with mortality for EOC overall and high-grade serous ovarian carcinoma (HGSOC). Results Overweight or obesity was associated with up to 51% and 104% increased mortality in EOC and HGSOC [Hazard Ratio (HR)] = 1.51, 95% CI = 1.05 to 2.19 and HR = 2.04, 95% CI = 1.29 to 3.21). Sarcopenia and overweight or obesity was associated with up to 66% and 67% increased mortality in EOC and HGSOC (HR = 1.66, 95% CI = 1.13 to 2.45 and HR = 1.67, 95% CI = 1.05 to 2.68). Sarcopenia or cachexia was associated with up to 73% and 109% increased mortality in EOC and HGSOC (HR = 1.73, 95% CI = 1.14 to 2.63 and HR = 2.09, 95% CI = 1.25 to 3.50). Conclusions Overweight or obesity, sarcopenia and overweight or obesity, and sarcopenia or cachexia phenotypes were each associated with increased mortality in EOC and HGSOC. Exercise and dietary interventions could be leveraged as ancillary treatment strategies for improving outcomes in the most fatal gynecological malignancy with no previously established modifiable prognostic factors. [ABSTRACT FROM AUTHOR]

Several reports of concurrent MYC , BCL2 , BCL6 , and CCND1 rearrangements in high-grade B-cell lymphoma (HGBL) have been recently described. Herein, we aimed to delineate the scope of this entity through a review of HGBL with a "quadruple-hit" genetic profile identified at our institution. We performed a retrospective review (2015-2023) at our institution of B-cell lymphoma (BCL) cases that were evaluated with concurrent MYC , BCL2 , and BCL6 break-apart and IGH::MYC and IGH::CCND1 dual-color dual-fusion fluorescence in situ hybridization studies. Of 203 cases meeting inclusion criteria, 2 (1%) with a quadruple-hit genetic profile were identified. Case 1 represented a 59-year-old female with widespread lymphadenopathy and a diagnosis of HGBL who exhibited primary refractoriness to dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) chemotherapy. Case 2 represented a 58-year-old male with mediastinal and abdominal lymphadenopathy and a diagnosis of large BCL who died from disease after 1 cycle of DA-EPOCH-R chemotherapy. Similarly, a literature review of 7 previously reported cases of HGBL with a quadruple-hit profile also demonstrated aggressive disease behavior. Our study adds 2 new cases to the rarely encountered quadruple-hit HGBL, and a brief meta-analysis of the 9 available cases indicates aggressive disease behavior conferred by this constellation of genetic events. [ABSTRACT FROM AUTHOR]

Objectives To determine the role of keratin 17 (K17) as a predictive biomarker for response to chemotherapy by defining thresholds of K17 expression based on immunohistochemical tests that could be used to optimize therapeutic intervention for patients with pancreatic ductal adenocarcinoma (PDAC). Methods We profiled K17 expression, a hallmark of the basal molecular subtype of PDAC, by immunohistochemistry in 2 cohorts of formalin-fixed, paraffin-embedded PDACs (n = 305). We determined a K17 threshold of expression to optimize prognostic stratification according to the lowest Akaike information criterion and explored the potential relationship between K17 and chemoresistance by multivariate predictive analyses. Results Patients with advanced-stage, low K17 PDACs treated using 5-fluorouracil (5-FU)–based chemotherapeutic regimens had 3-fold longer survival than corresponding cases treated with gemcitabine-based chemotherapy. By contrast, PDACs with high K17 did not respond to either regimen. The predictive value of K17 was independent of tumor mutation status and other clinicopathologic variables. Conclusions The detection of K17 in 10% or greater of PDAC cells identified patients with shortest survival. Among patients with low K17 PDACs, 5-FU–based treatment was more likely than gemcitabine-based therapies to extend survival. [ABSTRACT FROM AUTHOR]

Background The decline of physical function during chemotherapy predicts poor quality of life and premature death. It is unknown if resistance training prevents physical function decline during chemotherapy in colon cancer survivors. Methods This multicenter trial randomly assigned 181 colon cancer survivors receiving postoperative chemotherapy to home-based resistance training or usual care control. Physical function outcomes included the short physical performance battery, isometric handgrip strength, and the physical function subscale of the Medical Outcomes Short-Form 36-item questionnaire. Mixed models for repeated measures quantified estimated treatment differences. Results At baseline, participants had a mean (SD) age of 55.2 (12.8) years; 67 (37%) were 60 years or older, and 29 (16%) had a composite short physical performance battery score of no more than 9. Compared with usual care control, resistance training did not improve the composite short physical performance battery score (estimated treatment difference = −0.01, 95% confidence interval [CI] = −0.32 to 0.31; P  = .98) or the short physical performance battery scores for balance (estimated treatment difference = 0.01, 95% CI = −0.10 to 0.11; P  = .93), gait speed (estimated treatment difference = 0.08, 95% CI = −0.06 to 0.22; P  = .28), and sit-to-stand (estimated treatment difference = −0.08, 95% CI = −0.29 to 0.13; P  = .46). Compared with usual care control, resistance training did not improve isometric handgrip strength (estimated treatment difference = 1.50 kg, 95% CI = −1.06 to 4.05; P  = .25) or self-reported physical function (estimated treatment difference = −3.55, 95% CI = −10.03 to 2.94); P  = .28). The baseline short physical performance battery balance score (r  =   0.21, 95% CI = 0.07 to 0.35) and handgrip strength (r  =   0.23, 95% CI = 0.09 to 0.36) correlated with chemotherapy relative dose intensity. Conclusion Among colon cancer survivors with relatively high physical functioning, random assignment to home-based resistance training did not prevent physical function decline during chemotherapy. Clinical Trial Registration NCT03291951. [ABSTRACT FROM AUTHOR]

Background We evaluated whether the addition of docetaxel (D) to a combination comprising 5-fluorouracil/leucovorin (5-FU/LV) or capecitabine (C) plus oxaliplatin (O) (DOF/DOX) improved overall survival (OS) compared with 6 months of 5-fluorouracil (5-FU) or capecitabine in combination with oxaliplatin (FOLFOX/CAPOX) alone in advanced HER2-negative gastroesophageal junction and gastric adenocarcinomas (G/GEJ). Methods This study was an investigator-initiated, open-label, multi-institutional, randomized phase III trial in adult patients with HER2-negative advanced G/GEJs. The primary endpoint of the study was a comparison of median OS by Kaplan-Meier method. Next-generation sequencing was performed on tissue. Results Of the 324 patients randomly assigned between July 2020 and November 2022, 305 patients were evaluable for analysis (FOLFOX/CAPOX: 156; DOF/DOX: 149). With a median follow-up time of 19.2 months (95% Confidence Interval [CI] = 16.5 months to 21.9 months) for the entire cohort, the median OS was 10.1 months (95% CI = 9.2 to 10.9) for FOLFOX/CAPOX and 8.9 months (95% CI = 7.3 to 10.5) for DOF/DOX, and this difference was not statistically significant (P  = .70). An increased proportion of grade 3 or grade 4 neutropenia (21% vs 3%; P  < .001) and grade 2/3 neuropathy (17% vs 7%; P  = .005) was seen in patients receiving DOF/DOX. Genomic profiling revealed a low incidence of microsatellite instability (1%) and a high incidence of BRCA1 (8.4%) and BRCA2 (7.5%) somatic alterations. Conclusion FOLFOX or CAPOX chemotherapy for 6 months remains one of the standards of care in advanced HER2-negative gastroesophageal junction and gastric adenocarcinomas, with no additional survival benefit seen with the addition of docetaxel. Genomic profiling of patients revealed a higher than previously known incidence of somatic BRCA alterations, which requires further evaluation. CTRI (Clinical Trial Registry of India: CTRI/2020/03/023944). [ABSTRACT FROM AUTHOR]

Innovative strategies to increase clinical trial accessibility and equity are needed. We conducted a retrospective review of a phase II investigator-initiated trial to determine whether the modification of clinical trial design to decentralize study treatment can improve trial accessibility among underrepresented groups. Sociodemographic characteristics, including area deprivation indices, as well as study site travel distance, time, and costs were compared between enrolled participants who received chemotherapy locally and participants who did not. Participants who received chemotherapy locally lived substantially farther from the study site (median = 95.90 vs 25.20 miles, P  = .004), faced a greater time burden traveling to the study site (median = 115.00 vs 34.00 minutes, P  = .002), and had higher travel-related costs for a single trip to the study site (median = $62.81 vs $16.51, P  = .004). This study highlights opportunities for alleviating financial and time burdens associated with clinical trial participation, promoting equity in clinical research. Trial Registration: ClinicalTrials.gov identifier: NCT04380337. [ABSTRACT FROM AUTHOR]

Background and purpose: With the aging population, the number of elderly patients with colorectal cancer (CRC) is increasing. To date, elderly patients with stage Ⅱ CRC often receive a weakened chemotherapy regimen or even no chemotherapy after radical surgery, and It is still unclear whether this will lead to adverse oncological outcomes. This study aimed to explore the prognostic impact of advanced age on stage Ⅱ CRC patients after removing bias through a multivariate COX regression approach. Methods: We retrospectively collected data of 3314 colorectal cancer patients with postoperative pathology of stage Ⅱ, no history of previous tumors, no secondary primary tumors within 5 years after surgery and no preoperative neoadjuvant therapy. This study was reviewed by the medical ethics committee of Fudan University Shanghai Cancer Center (ethics number: 050432-4-2108*). The optimal threshold for calculating age relative to survival using survminer package of R software (version 3.0) (surv_cutpoint algorithm) was 73 years. We compared the clinical and pathological characteristics, overall survival (OS) and disease-free survival (DFS) between the older group (age>73 years) and the younger group (age≤73 years). The alignment diagram prediction model was drawn using the survival package and RMS package. Results: The elderly and non-elderly groups were evenly comparable in terms of gender, tumor location, differentiation, vascular invasion, perineural invasion and pT stage. Multivariate COX regression showed that advanced age was an independent prognostic risk factor for OS [hazard ratio (HR)=3.725 (3.051-4.549), P

Introduction This study investigated the efficacy and safety of neoadjuvant chemotherapy for locally advance penile squamous cell carcinoma for which current evidence is lacking. Methods Included patients had locally advanced penile squamous cell carcinoma with clinical lymph node metastasis treated with at least 1 dose of neoadjuvant chemotherapy prior to planned consolidative lymphadenectomy. Objective response rates were assessed using Response Evaluation Criteria in Solid Tumors v1.1. The primary and secondary outcomes were overall survival and progression-free survival, estimated by the Kaplan–Meier method. Treatment-related adverse events were graded per the Common Terminology Criteria for Adverse Events v5.0. Results A total of 209 patients received neoadjuvant chemotherapy for locally advanced and clinically node-positive penile squamous cell carcinoma. The study population consisted of 7% of patients with stage II disease, 48% with stage III, and 45% with stage IV. Grade 2 treatment-related adverse events occurred in 35 (17%) patients, and no treatment-related mortality was observed. Of the patients, 201 (97%) completed planned consolidative lymphadenectomy. During follow-up, 106 (52.7%) patients expired, with a median overall survival of 37.0 months (95% confidence interval [CI] = 23.8 to 50.1 months) and median progression-free survival of 26.0 months (95% CI = 11.7 to 40.2 months). Objective response rate was 57.2%, with 87 (43.2%) having partial response and 28 (13.9%) having a complete response. Patients with objective response to neoadjuvant chemotherapy had a longer median overall survival (73.0 vs 17.0 months, P  < .01) compared with those who did not. The lymph node pathologic complete response rate was 24.8% in the cohort. Conclusion Neoadjuvant chemotherapy with lymphadenectomy for locally advanced penile squamous cell carcinoma is well tolerated and active to reduce the disease burden and improve long-term survival outcomes. [ABSTRACT FROM AUTHOR]

Background Inequities in guideline-concordant treatment receipt contribute to worse survival in Black patients with breast cancer. Inequity-reduction interventions (eg, navigation, bias training, tracking dashboards) can close such treatment gaps. We simulated the population-level impact of statewide implementation of inequity-reduction interventions on racial breast cancer inequities in North Carolina. Methods Using registry-linked multipayer claims data, we calculated inequities between Black and White patients receiving endocrine therapy (n = 12 033) and chemotherapy (n = 1819). We then built cohort-stratified (endocrine therapy and chemotherapy) and race-stratified Markov models to simulate the potential increase in the proportion of patients receiving endocrine therapy or chemotherapy and subsequent improvements in breast cancer outcomes if inequity-reducing intervention were implemented statewide. We report uncertainty bounds representing 95% of simulation results. Results In total, 75.6% and 72.1% of Black patients received endocrine therapy and chemotherapy, respectively, over the 2006-2015 and 2004-2015 periods (vs 79.3% and 78.9% of White patients, respectively). Inequity-reduction interventions could increase endocrine therapy and chemotherapy receipt among Black patients to 89.9% (85.3%, 94.6%) and 85.7% (80.7%, 90.9%). Such interventions could also decrease 5-year and 10-year breast cancer mortality gaps from 3.4 to 3.2 (3.0, 3.3) and from 6.7 to 6.1 (5.9, 6.4) percentage points in the endocrine therapy cohorts and from 8.6 to 8.1 (7.7, 8.4) and from 8.2 to 7.8 (7.3, 8.1) percentage points in the chemotherapy cohorts. Conclusions Inequity-focused interventions could improve cancer outcomes for Black patients, but they would not fully close the racial breast cancer mortality gap. Addressing other inequities along the cancer continuum (eg, screening, pre- and postdiagnosis risk factors) is required to achieve full equity in breast cancer outcomes. [ABSTRACT FROM AUTHOR]

Intradural spinal metastases significantly impair neurological function and quality of life, necessitating multimodal, palliative management to preserve mobility and alleviate pain. The effectiveness of systemic chemotherapy and radiotherapy is limited due to the blood-spinal cord barrier and the tumours' radioresistance, respectively. This highlights the urgency for alternative treatments given the rapid neurological decline. Surgical intervention becomes crucial, focusing on maximum tumour debulking to enhance disease control, restore ambulation, and palliate symptoms without compromising neurological function. Achieving this involves meticulous preoperative planning and aggressive intraoperative neuromonitoring. Combining surgery with adjuvant therapies may improve local control and potentially delay recurrence. This case-based review emphasizes the surgical considerations and outcomes in two cases of intradural spinal metastases, underscoring the value of surgery in multimodal therapy. [ABSTRACT FROM AUTHOR]

Tumors of the inferior vena cava (IVC) are rare and usually malignant and they can be primary and secondary. The most common primary tumor of the IVC is primary leiomyosarcoma. The first case of primary IVC leiomyosarcoma has been described in 1871 [ 1 ].The total number of 218 cases has collected until 1996 [ 2 ]. After that, three large single center series of these tumors emerged [ 3 – 5 ]. Present a series of five cases of these tumors. All the patients underwent a wide complete resection of tumors and the reconstruction with Dacron grafts. One patient died 19 months after the surgery, while the remaining ones survived without a local and system disease relapse. Although a surgical resection combined with the chemotherapy is often not curative, it can achieve a significant long-term survival. For this reason, we recommend the aggressive surgical management using the modern vascular surgical and oncology techniques. [ABSTRACT FROM AUTHOR]

Background In KEYNOTE-355 (NCT02819518), the addition of pembrolizumab to chemotherapy led to statistically significant improvements in progression-free survival and overall survival in patients with advanced triple-negative breast cancer with tumor programmed cell death ligand 1 (PD-L1) combined positive score of at least 10. We report patient-reported outcomes from KEYNOTE-355. Methods Patients were randomly assigned 2:1 to pembrolizumab 200 mg or placebo every 3 weeks for up to 35 cycles plus investigator's choice chemotherapy (nab-paclitaxel, paclitaxel, or gemcitabine plus carboplatin). The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Core 30 (QLQ-C30), Breast Cancer–Specific Quality of Life Questionnaire, and EuroQol 5-Dimension questionnaire visual analog scale were prespecified. Patient-reported outcomes were analyzed for patients who received at least 1 dose of study treatment and completed at least 1 patient-reported outcome assessment. Changes in patient-reported outcome scores from baseline were assessed at week 15 (latest time point at which completion and compliance rates were at least 60% and at least 80%, respectively). Time to deterioration in patient-reported outcomes was defined as time to first onset of at least a 10-point worsening in score from baseline. Results Patient-reported outcome analyses included 317 patients with tumor PD-L1 combined positive score of at least 10 (pembrolizumab plus chemotherapy: n = 217; placebo plus chemotherapy: n = 100). There were no between-group differences in change from baseline to week 15 in QLQ-C30 global health status/quality of life (QOL; least-squares mean difference = −1.81, 95% confidence interval [CI] = −6.92 to 3.30), emotional functioning (least-squares mean difference = −1.43, 95% CI = −7.03 to 4.16), physical functioning (least-squares mean difference = −1.05, 95% CI = −6.59 to 4.50), or EuroQol 5-Dimension questionnaire visual analog scale (least-squares mean difference = 0.18, 95% CI = −5.04 to 5.39) and no between-group difference in time to deterioration in QLQ-C30 global health status/QOL, emotional functioning, or physical functioning. Conclusions Together with the efficacy and safety findings, patient-reported outcome results from KEYNOTE-355 support pembrolizumab plus chemotherapy as a standard of care for patients with advanced triple-negative breast cancer with tumor PD-L1 expression (combined positive score ≥10). [ABSTRACT FROM AUTHOR]

Primary thyroid lymphoma is a rare thyroid cancer, comprising ˂5% of thyroid neoplasms. Most cases are diffuse large B-cell lymphoma (DLBCL). Coexistence with papillary thyroid cancer (PTC) is extremely rare. This study presents a case of a 55-year-old woman with DLBCL and micropapillary thyroid cancer who underwent lobectomy, chemotherapy, and radiotherapy. Additionally, we performed a systematic review of 10 cases, including the reported case. The risk of bias in case reports varied. DLBCL diagnoses were mainly made after surgery, with total thyroidectomy being the most common surgical procedure. Chemotherapy was administered in most cases, and radiotherapy was used in some cases. Long-term outcomes indicated a low recurrence rate. While some debate the role of surgery in thyroid lymphoma, this study suggests that surgery should be considered in selected cases. Further research is needed to determine optimal treatment strategies for DLBCL with PTC. [ABSTRACT FROM AUTHOR]

Background and purpose: With the aging population, the number of elderly patients with colorectal cancer (CRC) is increasing. To date, elderly patients with stage II CRC often receive a weakened chemotherapy regimen or even no chemotherapy after radical surgery, and It is still unclear whether this will lead to adverse oncological outcomes. This study aimed to explore the prognostic impact of advanced age on stage II CRC patients after removing bias through a multivariate COX regression approach. Methods: We retrospectively collected data of 3314 colorectal cancer patients with postoperative pathology of stage II, no history of previous tumors, no secondary primary tumors within 5 years after surgery and no preoperative neoadjuvant therapy. This study was reviewed by the medical ethics committee of Fudan University Shanghai Cancer Center (ethics number: 050432-4-2108*). The optimal threshold for calculating age relative to survival using survminer package of R software (version 3.0) (surv_cutpoint algorithm) was 73 years. We compared the clinical and pathological characteristics, overall survival (OS) and disease-free survival (DFS) between the older group (age-73 years) and the younger group (age≤73 years). The alignment diagram prediction model was drawn using the survival package and RMS package. Results: The elderly and non-elderly groups were evenly comparable in terms of gender, tumor location, differentiation, vascular invasion, perineural invasion and pT stage. Multivariate COX regression showed that advanced age was an independent prognostic risk factor for OS -hazard ratio (HR)=3.725 (3.051-4.549), P<0.001 and DFS HR=2.431 (2.029-2.912), P0.001. The nomogram (alignment diagram) prediction model constructed based on multivariate COX regression could effectively evaluate the prognosis of stage CRC patients and provide guidance for practical clinical work. Conclusion: In stage CRC patients, older age is associated with shorter OS and DFS. Adequate intensity of adjuvant chemotherapy may be necessary. Treatment decisions can be adjusted based on the predicted model scores of the patient's alignment diagram. [ABSTRACT FROM AUTHOR]

Background No study has quantified the impact of pain and other adverse health outcomes on global physical and mental health in long-term US testicular cancer survivors or evaluated patient-reported functional impairment due to pain. Methods Testicular cancer survivors given cisplatin-based chemotherapy completed validated surveys, including Patient-Reported Outcomes Measurement Information System v1.2 global physical and mental health, Patient-Reported Outcomes Measurement Information System pain questionnaires, and others. Multivariable linear regression examined relationships between 25 adverse health outcomes with global physical and mental health and pain-interference scores. Adverse health outcomes with a β ^  of more than 2 are clinically important and reported below. Results Among 358 testicular cancer survivors (median age = 46 years, interquartile range [IQR] = 38–53 years; median time since chemotherapy = 10.7 years, IQR = 7.2–16.0 years), median adverse health outcomes number was 5 (IQR = 3–7). A total of 12% testicular cancer survivors had 10 or more adverse health outcomes, and 19% reported chemotherapy-induced neuropathic pain. Increasing adverse health outcome numbers were associated with decreases in physical and mental health (P  <  .0001 each). In multivariable analyses, chemotherapy-induced neuropathic pain (⁠ β ^ = −3.72; P  =  .001), diabetes (⁠ β ^ = −4.41; P  =  .037), obesity (⁠ β ^ = −2.01; P  =  .036), and fatigue (⁠ β ^ = −8.58; P  <  .0001) were associated with worse global mental health, while being married or living as married benefited global mental health (⁠ β ^  = 3.63; P  =  .0006). Risk factors for pain-related functional impairment included lower extremity location (⁠ β ^  = 2.15; P  =  .04) and concomitant peripheral artery disease (⁠ β ^  = 4.68; P  <  .001). Global physical health score reductions were associated with diabetes (⁠ β ^ = −3.81; P  =  .012), balance or equilibrium problems (⁠ β ^ = −3.82; P  =  .003), cognitive dysfunction (⁠ β ^ = −4.43; P  <  .0001), obesity (⁠ β ^ = −3.09; P  <  .0001), peripheral neuropathy score (⁠ β ^ = −2.12; P  <  .0001), and depression (⁠ β ^ = −3.17; P  <  .0001). Conclusions Testicular cancer survivors suffer adverse health outcomes that negatively impact long-term global mental health, global physical health, and pain-related functional status. Clinically important factors associated with worse physical and mental health identify testicular cancer survivors requiring closer monitoring, counseling, and interventions. Chemotherapy-induced neuropathic pain must be addressed, given its detrimental impact on patient-reported functional status and mental health 10 or more years after treatment. [ABSTRACT FROM AUTHOR]

Background The Surgery in Early Metastatic Seminoma (SEMS) trial examined retroperitoneal lymph node dissection as first-line treatment for patients with isolated 1-3 cm retroperitoneal lymphadenopathy. To date, the standard of care for these patients has been either chemotherapy or radiotherapy. Herein, we evaluated the relative cost-effectiveness of these management strategies. Methods A microsimulation model assessed the cost-effectiveness of retroperitoneal lymph node dissection, chemotherapy, and radiotherapy for stage IIA seminoma. Sensitivity analyses were performed to evaluate model robustness. Retroperitoneal lymph node dissection recurrence probabilities were obtained from the SEMS trial. All other probability and utility values were obtained from published literature. Primary outcomes included costs from a commercial insurer's perspective, effectiveness (quality adjusted life-years [QALYs]), and incremental cost-effectiveness ratios using a willingness-to-pay threshold of $100 000/QALY. Results At a lifetime horizon, the mean costs per patient for retroperitoneal lymph node dissection, radiotherapy, and chemotherapy were $58 469, $98 783, and $104 096, and the mean QALYs were 40.61, 40.70, and 39.15, respectively. Retroperitoneal lymph node dissection was found to be the most cost-effective approach because of high costs and accrued disutility of chronic toxicities associated with radiotherapy (cost-effectiveness ratios = $433 845/QALY) and chemotherapy (dominated). On 1-way sensitivity analyses, retroperitoneal lymph node dissection was no longer cost-effective if the probabilities of infertility and cardiovascular toxicity after radiotherapy were less than 13% and 16%, respectively, or if the 2-year probability of progression after retroperitoneal lymph node dissection was more than 26%. Conclusions Retroperitoneal lymph node dissection was the most cost-effective treatment approach for stage IIA seminoma. These findings support clinical guideline consideration of including retroperitoneal lymph node dissection as a treatment option for well-selected patients with stage IIA seminoma. [ABSTRACT FROM AUTHOR]

Progress in the development of effective chemotherapy is producing a growing population of patients with acute and chronic painful chemotherapy-induced peripheral neuropathy (CIPN), a serious treatment-limiting side effect for which there is currently no US Food and Drug Administration-approved treatment. CIPNs induced by diverse classes of chemotherapy drugs have remarkably similar clinical presentations, leading to the suggestion they share underlying mechanisms. Sensory neurons share with immune cells the ability to detect damage associated molecular patterns (DAMPs), molecules produced by diverse cell types in response to cellular stress and injury, including by chemotherapy drugs. DAMPs, in turn, are ligands for pattern recognition receptors (PRRs), several of which are found on sensory neurons, as well as satellite cells, and cells of the immune system. In the present experiments, we evaluated the role of two PRRs, TLR4 and RAGE, present in dorsal root ganglion (DRG), in CIPN. Antisense (AS)-oligodeoxynucleotides (ODN) against TLR4 and RAGE mRNA were administered intrathecally before ('prevention protocol') or 3 days after ('reversal protocol') the last administration of each of three chemotherapy drugs that treat cancer by different mechanisms (oxaliplatin, paclitaxel and bortezomib). TLR4 and RAGE AS-ODN prevented the development of CIPN induced by all three chemotherapy drugs. In the reversal protocol, however, while TLR4 AS-ODN completely reversed oxaliplatin- and paclitaxel-induced CIPN, in rats with bortezomib-induced CIPN it only produced a temporary attenuation. RAGE AS-ODN, in contrast, reversed CIPN induced by all three chemotherapy drugs. When a TLR4 antagonist was administered intradermally to the peripheral nociceptor terminal, it did not affect CIPN induced by any of the chemotherapy drugs. However, when administered intrathecally, to the central terminal, it attenuated hyperalgesia induced by all three chemotherapy drugs, compatible with a role of TLR4 in neurotransmission at the central terminal but not sensory transduction at the peripheral terminal. Finally, since it has been established that cultured DRG neurons can be used to study direct effects of chemotherapy on nociceptors, we also evaluated the role of TLR4 in CIPN at the cellular level, using patch-clamp electrophysiology in DRG neurons cultured from control and chemotherapy-treated rats. We found that increased excitability of small-diameter DRG neurons induced by in vivo and in vitro exposure to oxaliplatin is TLR4-dependent. Our findings suggest that in addition to the established contribution of PRR-dependent neuroimmune mechanisms, PRRs in DRG cells also have an important role in CIPN. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide OBJECTIVES The goal of this project was to evaluate the effect of surgical treatment and the long-term survival of patients with staged IE/IIE pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma. METHODS From January 2004 to December 2018, we retrospectively analysed 96 patients diagnosed with low-stage primary pulmonary MALT lymphoma according to the modified Ann Arbor staging system (IE/IIE). We compared the outcomes of different treatment modalities for staged IE/IIE MALT lymphoma. Progression-free survival (PFS) and overall survival were estimated using Kaplan-Meier curves, and the differences were compared using the log-rank test. The Cox proportional hazards model was used in this study. RESULTS The median PFS time of low-staged MALT lymphomas was 118 months. The overall survival and PFS of the radical surgery group and the biopsy + chemotherapy group suggested no significant difference (P  =   0.63, P  =   0.65). Patients positive for Blc-2 and Ki-67 suffered from a compromised PFS (P  =   0.023, P  =   0.006). The Cox adjusted proportional hazards model analysis suggested that surgical procedures were not protective factors for patients with low-staged (IE/IIE) pulmonary MALT lymphoma, whereas being positive for Blc-2 and Ki-67 was a risk factor for patients with low-staged pulmonary MALT lymphoma (hazard ratio: 9.567; P =  0.044; hazard ratio: 6.042, P =  0.049). CONCLUSIONS Our findings suggested that for staged IE/IIE pulmonary MALT lymphoma, radical surgical resection did not provide a survival benefit compared with chemotherapy after biopsy. Thus, radical surgery may be avoided unless biopsy is necessary for a diagnosis that requires sublobar resection. For those lesions that were Blc-2- or Ki-67-positive, compromised survival may be suggested. [ABSTRACT FROM AUTHOR]

The prognosis of recurrent gastric cancer is generally poor, and aggressive surgical treatment is rarely performed. Herein, we present the case of a patient who underwent resection of cerebellar and adrenal gland metastases from gastric cancer. The patient was treated for gastric cancer with distal gastrectomy at 23 years and for remnant gastric cancer with completion gastrectomy at 48 years. At 59 years old, she experienced vertigo and nausea and was diagnosed with cerebellar and left adrenal gland tumours. First, the cerebellar tumours were resected and diagnosed as metastases of gastric cancer. After 1 month, the adrenal gland tumour was resected and diagnosed as metastatic. She underwent whole-brain radiotherapy and subsequent chemotherapy with S-1. One year after the surgery, the patient died of meningitis carcinomatosa. There are few reports on long-term survival after the resection of brain metastases. Herein, we report our experience along with a review of the literature. [ABSTRACT FROM AUTHOR]

Opinion statement: In our clinical practice, we have shifted away from the use of adjuvant normothermic intraperitoneal (IP) chemotherapy, particularly following the publication of GOG 252. Our decision is rooted in the accumulating evidence indicating a lack of demonstrable superiority, alongside the recognized toxicities and logistical challenges associated with its administration. This strategic departure is also influenced by the rising utilization of maintenance therapies such as bevacizumab and PARP inhibitors, which present viable alternatives for improving patient outcomes. Our utilization of hyperthermic IP chemotherapy (HIPEC) is currently reserved for a specific cohort of patients, mirroring the patient population studied in the OVHIPEC-1 trial. Specifically, our HIPEC protocol applies to patients presenting with newly diagnosed stage IIIC high-grade epithelial ovarian cancer who are deemed ineligible for primary debulking surgery. Patients must exhibit at least stable disease with neoadjuvant platinum-based chemotherapy, maintain a favorable performance status (ECOG score 0–1), possess good nutritional reserves (with no evidence of protein-calorie malnutrition and an albumin level exceeding 3.5), and not have chronic kidney disease. When HIPEC is planned, it is administered at the time of interval debulking surgery, contingent upon the attainment of optimal surgical outcomes (< 1 cm of residual disease). Our HIPEC protocol adheres to the original OVHIPEC-1 trial guidelines, employing cisplatin at a dosage of 100 mg/m2. We administer at least two antiemetics, antihistamines, and sodium thiosulfate to mitigate known side effects. Postoperatively, patients are admitted to the general surgical floor, reserving the intensive care unit for those in critical condition. We follow Enhanced Recovery After Surgery principles, incorporating early ambulation and feeding into our postoperative care strategy. We have encountered encouraging results with this approach, with most patients having largely uncomplicated postoperative courses and resuming adjuvant chemotherapy within 3 to 4 weeks of surgery. [ABSTRACT FROM AUTHOR]

Introduction The addition of taxanes to anthracycline-based chemotherapy is considered standard of care in the treatment of breast cancer. However, there are insufficient data regarding the safety of taxanes during pregnancy. The aim of this study was to describe the incidence of obstetric and neonatal adverse events associated with the use of taxane-containing chemotherapy regimens for the treatment of breast cancer during pregnancy. Methods This is a multicenter, international cohort study of breast cancer patients treated with taxanes during pregnancy. A descriptive analysis was undertaken to synthetize available data. Results A total of 103 patients were included, most of whom were treated with paclitaxel and anthracyclines given in sequence during gestation (90.1%). The median gestational age at taxane initiation was 28 weeks (range = 12-37 weeks). Grade 3-4 adverse events were reported in 7 of 103 (6.8%) patients. The most common reported obstetric complications were intrauterine growth restriction (n = 8 of 94, 8.5%) and preterm premature rupture of membranes (n = 5 of 94, 5.3%). The live birth rate was 92 of 94 (97.9%), and the median gestational age at delivery was 37 weeks (range = 32-40 weeks). Admission to an intensive care unit was reported in 14 of 88 (15.9%) neonates, and 17 of 70 (24.3%) live births resulted in small for gestational age neonates. Congenital malformations were reported in 2 of 93 (2.2%). Conclusion Obstetric and neonatal outcomes after taxane exposure during pregnancy were generally favorable and did not seem to differ from those reported in the literature with standard anthracycline-based regimens. This study supports the use of taxanes during gestation when clinically indicated. [ABSTRACT FROM AUTHOR]

Background Treatment of childhood glioma has evolved to reduce radiotherapy exposure with the goal of limiting late toxicity. However, the associations between treatment changes and neurocognition, and the contribution of neurocognition and chronic health conditions to attainment of adult independence, remain unknown. Methods Adult survivors of childhood glioma diagnosed in 1970-1999 in the Childhood Cancer Survivor Study (n = 1284; median [minimum-maximum] 30 [18-51] years of age at assessment; 22 [15-34] years from diagnosis) self-reported neurocognitive impairment and chronic health conditions. Multivariable models evaluated associations between changes in treatment exposures (surgery only, chemotherapy [with or without surgery], cranial radiation [with or without chemotherapy and/or surgery]), and neurocognitive impairment. Latent class analysis with 5 indicators (employment, independent living, assistance with routine and/or personal care needs, driver's license, marital or partner status) identified classes of functional independence. Path analysis tested associations among treatment exposures, neurocognitive impairment, chronic health conditions, and functional independence. Statistical tests were 2-sided. Results Cranial radiation exposure decreased over time (51%, 1970s; 46%, 1980s; 27%, 1990s]. However, compared with siblings, survivors with any treatment exposure were at elevated risk for neurocognitive impairment, including surgery only (eg, memory: relative risk = 2.22; task efficiency: relative risk = 1.88; both P  < .001). Three classes of functional independence were identified: independent (58%), moderately independent (20%), and nonindependent (22%). Cranial radiation was associated with nonindependence through impaired task efficiency (β = 0.06), sensorimotor (β = 0.06), and endocrine (β = 0.10) chronic health conditions and through the associations between these conditions and task efficiency (each β = 0.04). Sensorimotor and endocrine chronic health conditions were associated with nonindependence through memory. Conclusion Most long-term glioma survivors achieve adult independence. However, functional nonindependence is associated with treatment-related neurocognitive impairment and chronic health conditions. [ABSTRACT FROM AUTHOR]

Background High tumour budding has been indicated as a risk factor of poor survival in colorectal cancer. This study aimed to investigate the impact of tumour budding grades and the use of adjuvant chemotherapy on prognosis in patients with colorectal cancer. Methods This study included consecutive colorectal cancer patients who underwent radical surgery for primary colorectal adenocarcinoma at The Sixth Hospital of Sun Yat-sen University between 2009 and 2019. Tumour budding was assessed based on the recommendations of the International Tumor Budding Consensus Conference using haematoxylin and eosin (H&E)-stained slides with tumour samples. The primary outcome of interest was to correlate tumour budding with disease-free survival and overall survival; the secondary outcome was investigation of the impact of adjuvant therapy on different tumour budding grades. In addition, a subgroup analysis was performed for the effects of lymphocytic infiltration on adjuvant chemotherapy in patients with Bd3. Results Of 709 eligible patients, 412 with colorectal cancer were included. According to the International Tumor Budding Consensus Conference, 210 (50.9 per cent), 127 (30.8 per cent) and 75 (18.2 per cent) were classified as low budding (Bd1), intermediate budding (Bd2) and high budding (Bd3) respectively. Patients with Bd1, Bd2 and Bd3 had 5-year disease-free survival rates of 82.9 per cent, 70.1 per cent and 49.3 per cent respectively, and 5-year overall survival rates of 90 per cent, 79.5 per cent and 62.7 per cent respectively (P <0.001). Adjuvant chemotherapy yielded a significant survival benefit in patients with Bd3 (5-year disease-free survival, 65 per cent versus 31.4 per cent, P <0.001; 5-year overall survival, 84.4 per cent versus 63.1 per cent, P <0.001), but not in those with Bd1 or Bd2. In patients with Bd3, the benefit of adjuvant chemotherapy was maintained in those with low, but not high lymphocytic infiltration. Conclusion High grade of tumour budding was strongly correlated with poorer survival outcomes in colorectal cancer. Patients with Bd3 benefited from adjuvant chemotherapy, with the exclusion of patients with high lymphocytic infiltration. [ABSTRACT FROM AUTHOR]

Background The Patient Cloud ePRO app was adopted by the National Cancer Institute National Clinical Trials Network (NCTN) to facilitate capturing electronic patient-reported (ePRO) outcome data, but use has been low. The study objectives were to test whether a patient-targeted ePRO educational resource (ePRO-E) would increase ePRO intent (number of users) and improve data quality (high quality: ≥80% of the required surveys submitted) within an ongoing NCTN study. Methods The ePRO-E intervention, a patient-targeted educational resource (written material and 6-minute animated YouTube video), was designed to address ePRO barriers. ePRO intent and data quality were compared between 2 groups (N  =   69): a historical control group and a prospectively recruited intervention group exposed to ePRO-E. Covariates included technology attitudes, age, sex, education, socioeconomic status, and comorbidity. Results Intervention group ePRO intent (78.8%) was statistically significantly higher than historical control group intent (47.1%) (P  =  .03). Patients choosing ePRO versus paper surveys had more positive and higher technology attitudes scores (P  =  .03). The odds of choosing ePRO were 4.7 times higher (95% Confidence Interval [CI] = 1.2 to 17.8) (P  =  .02) among intervention group patients and 5.2 times higher (95% CI = 1.3 to 21.6) (P = .02) among patients with high technology attitudes scores, after controlling for covariates. However, the 80% submission rate (percentage submitting ≥80% of required surveys) in the ePRO group (30.6%) was statistically significantly lower than in the paper group (57.9%) (P  =  .05). Conclusions ePRO-E exposure increased ePRO intent. High technology attitudes scores were associated with ePRO selection. Since the ePRO survey submission rate was low, additional strategies are needed to promote high-quality data submission. [ABSTRACT FROM AUTHOR]

Background Many women diagnosed with cancer as adolescents and young adults (AYAs, age 15-39 years) want biological children after cancer but lack information on the potential impact of their cancer history on future reproductive outcomes. We investigated the risk of adverse birth outcomes among AYA cancer survivors. Methods We identified insured women diagnosed with AYA breast cancer, thyroid cancer, gynecologic cancers, lymphoma, or melanoma from 2003 to 2016 in the state of North Carolina or the Kaiser Permanente health care systems in northern and southern California. Post-diagnosis births to cancer survivors were each matched with up to 5 births to women without cancer. Risk ratios for preterm birth (<37 completed weeks), very preterm birth (<34 completed weeks), low birth weight (<2500 g), and small for gestational age (SGA, <10th percentile of weight for gestational age) were estimated using modified Poisson regression. Results Analyses included 1648 births to 1268 AYA cancer survivors and 7879 births to 6066 women without cancer. Overall, risk of preterm birth, very preterm birth, low birth weight, and SGA did not significantly differ between births to women with and without cancer. However, births to women with gynecologic cancers had a significantly increased risk of low birth weight (risk ratio = 1.82; 95% confidence interval: 1.03 to 3.21) and suggested increased risk of preterm birth (risk ratio = 1.59; 95% confidence interval: 0.99 to 2.54). Chemotherapy exposure was not associated with increased risk of adverse birth outcomes. Conclusions Women with gynecologic cancers, but not other cancers, had an increased risk of adverse birth outcomes compared to women without cancer. [ABSTRACT FROM AUTHOR]

Primary hepatic rhabdomyosarcoma is an exceedingly rare type of sarcomas. A 15-year-old boy was admitted to the hospital with abdominal pain. Serial investigation showed a giant heterogeneous mass, with a diameter of 15 cm, located in the right lobe of the liver (segment 4a, 4b, 5, 6, 7, 8), with clear margins, non-homogeneous density in computerized tomography and the Positron Emission Tomography Scan Multi Slice revealed a peripherally slightly metabolically active hepatic mass (205 × 134 × 208 mm). Histopathological examination and the Immunohistochemical showed embryonal rhabdomyosarcoma. The management strategy involved multiple cycles of ifosfamide and doxorubicin and monitoring the tumor size, until the tumor size was suitable for the surgery. The management of hepatic rhabdomyosarcoma is a surgical challenge due to the late onset of symptoms, a limited number of reported cases, and poor prognosis. Surgical excision is the treatment of choice for primary hepatic rhabdomyosarcoma and combination between chemotherapy, surgery showed good results. [ABSTRACT FROM AUTHOR]

A 52-year-old gentleman presented with symptoms of breathlessness and type 1 respiratory failure. His CT pulmonary angiogram showed a heterogenous, oval-shaped lesion between the heart and diaphragm with a right atrial (RA) filling defect, pericardial thickening and pulmonary metastasis. An RA debulking salvage operation confirmed this to be a pericardial tumour and further cytology and immunohistochemistry testing confirmed a primary synovial sarcoma. After 12 days in intensive care for ventilation, the patient was successfully discharged on warfarin and underwent oncology follow-up for chemotherapy. Following a 15-month follow-up, no mortality was observed despite the aggressive nature of the tumour. [ABSTRACT FROM AUTHOR]

A female in her 60s with vague abdominal symptoms was found to have a pancreatic mass in her CT scan. A core needle biopsy done endoscopically demonstrated a poorly differentiated adenocarcinoma. The patient completed nine cycles of neoadjuvant systemic mFOLFIRINOX. Repeat staging demonstrated a partial radiographic response. She underwent an open pylorus-preserving pancreatoduodenectomy with segmental superior mesenteric vein resection with primary reconstruction (ISGPS Type 3). The final pathology demonstrated a poorly differentiated adenosquamous carcinoma, R1 margin status. The case report demonstrates the effect of mFOLFIRINOX on pancreatic adenosquamous (PASC) carcinoma with a review of the microscopic pictures following the neoadjuvant therapy. It can be postulated that glandular component being the major component in a PASC has a good response to mFOLFIRINOX like that seen in pancreatic ductal adenocarcinoma with some presumed effect on the squamous component as well. From the above case report, we are proposing that mFOLFIRINOX can be an effective chemotherapy regime in the management of PASC. [ABSTRACT FROM AUTHOR]

A 41-year-old male presented with a swelling in the right flank present since 2 years. Initially, it was small in size but increased in size for the past 6 months. Examination revealed a large swelling in the right flank that was soft in consistency and attached to the deeper muscle. CT scan revealed a heterogenous complex swelling with attachment to the underlying muscle. Core biopsy of the lesion was reported as undifferentiated sarcoma. After immunohistochemistry markers, the diagnosis was revised to a malignancy of a lymphomatous origin. Gene sequencing studies and extensive higher marker studies were done and a final diagnosis of plasmacytic infiltrate of uncertain clinical significance was reported. With no further diagnostic options available, the case still remains to be a diagnostic challenge as the choice of treatment between surgical resection and nonsurgical treatment with chemotherapy and/or radiation cannot be decided upon. [ABSTRACT FROM AUTHOR]

The recurrence rate following thymoma surgery has been reported to be as high as 29%. In cases of localized recurrence, complete resection can result in prolonged patient survival. However, surgery is rarely considered in cases of invasive recurrent thymomas with high disease burden. Here, we present the case of a woman with type B2 thymoma (Masaoka–Koga stage IVa) treated with surgery, chemotherapy, and radiotherapy. The disease recurred 6 years later, with invasion of the left lung and the 12th thoracic vertebra, as well as extension into the retroperitoneum. Due to the development of chemotherapy-associated toxicity, she underwent surgery with complete tumor resection and has remained free of disease at a 12-months follow-up. Radical surgery for recurrent invasive thymoma extending through the diaphragm is a feasible and safe therapeutic option in highly selected patients who are not eligible for systemic treatments. [ABSTRACT FROM AUTHOR]

In the context of colorectal cancer, splenic and ovarian metastases are rare outside of widely disseminated disease. Growing evidence suggests that 'oligometastatic' or limited metastatic disease can be treated surgically with good oncological outcomes. Splenic and ovarian metastases are not well represented in studies of oligometastatic colorectal cancer, resulting in uncertainty in the best management for these patients. We present the case of a 78-year-old woman diagnosed with oligometastatic colorectal cancer to bilateral ovaries and spleen, 5 years after resection of a primary colon cancer. The patient was treated with a bilateral salpingo-oopherectomy and subsequent open splenectomy. We discuss the role of surgery and peri-operative chemotherapy in the management of oligometastatic colorectal cancer involving atypical sites. [ABSTRACT FROM AUTHOR]

Objectives Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is historically associated with Helicobacter pylori (HP) infections in more than 80% of patients. However, the incidence of HP-negative MALT lymphoma has been increasing. The clinicopathologic features have not been well studied, and optimal management strategies remain unclear. Methods The pathology database was searched for primary gastric MALT lymphomas diagnosed from 2000 to 2017. The clinical data and the slides were reviewed. The cases were divided for analysis into those with a background of chronic gastritis with HP, chronic gastritis without HP, and without either a background of chronic gastritis or HP. Results Of 70 gastric MALT lymphoma cases identified, 26 (37% of total) had chronic gastritis and were positive for HP histologically (n = 23) or were HP positive by additional laboratory testing (n = 3). The remaining 44 (63% of total) cases were HP negative by histology. Within the HP-negative cases, 5 (11% of HP-negative cases) showed histologic gastritis while 39 (89% of HP-negative cases) did not have sufficient evidence of gastritis through review of slides (n = 18) or based on available pathology reports (n = 21). The HP-negative cases without gastritis had higher propensities to show a mass lesion on endoscopy compared with HP-positive cases (37.5% vs 11.1%, P =.02) at the initial diagnosis. The immunophenotype and rate of positive B-cell gene rearrangement were not significantly different between the 2 groups. While all HP-positive patients received antibiotics for HP eradication, treatment in the HP-negative group varied among antibiotics, radiation, rituximab, or chemotherapy. Among HP-negative patients with available follow-up, 13 (39%) showed disease recurrence, similar to the recurrence rate in HP-positive patients; however, no individual from either group has died of the disease thus far. Conclusions The incidence of HP-negative MALT lymphoma is increasing, and in our practice, it is currently more common than HP-associated MALT lymphomas. The pathophysiology of HP-negative MALT lymphoma without chronic gastritis remains unclear. Follow-up data in our study suggest that the prognosis of these cases is excellent despite varied management modalities. [ABSTRACT FROM AUTHOR]

Primary sarcomas of the breast are extremely rare and heterogenous malignancies; they should be differentiated from phyllodes tumors. They are characterized by their high rate of recurrence, rapid growth and aggressive coarse. We present a case of a 41-year-old Palestinian female who presented with a recurrent breast mass. Biopsy showed primary sarcoma and imaging confirmed metastasis to axillary lymph nodes. The patient received six cycles of ifosfamide–adriamycin protocol resulting in complete pathological response. She underwent left sided modified radical mastectomy followed by radiation and six more cycles of the same protocol as adjuvant. Primary breast sarcomas are rare neoplasms that require multidisciplinary discussion to guide treatment. The approach to these tumors is chemotherapy followed by surgical resection when operable, in addition to local control via radiotherapy and adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Background The UK National Health Service's Predict is a clinical tool widely used to estimate the prognosis of early-stage breast cancer. The performance of Predict for a second primary breast cancer is unknown. Methods Women 18 years of age or older diagnosed with a first or second invasive breast cancer between 2000 and 2013 and followed for at least 5 years were identified from the US Surveillance, Epidemiology, and End Results (SEER) database. Model calibration of Predict was evaluated by comparing predicted and observed 5-year breast cancer–specific mortality separately by estrogen receptor status for first vs second breast cancer. Receiver operating characteristic curves and areas under the curve were used to assess model discrimination. Model performance was also evaluated for various races and ethnicities. Results The study population included 6729 women diagnosed with a second breast cancer and 357 204 women with a first breast cancer. Overall, Predict demonstrated good discrimination for first and second breast cancers (areas under the curve ranging from 0.73 to 0.82). Predict statistically significantly underestimated 5-year breast cancer mortality for second estrogen receptor–positive breast cancers (predicted-observed = ‒6.24%, 95% CI = ‒6.96% to ‒5.49%). Among women with a first estrogen receptor–positive cancer, model calibration was good (predicted-observed = ‒0.22%, 95% CI = ‒0.29% to ‒0.15%), except in non-Hispanic Black women (predicted-observed = ‒2.33%, 95% CI = ‒2.65% to ‒2.01%) and women 80 years of age or older (predicted-observed = ‒3.75%, 95% CI = ‒4.12% to ‒3.41%). Predict performed well for second estrogen receptor–negative cancers overall (predicted-observed = ‒1.69%, 95% CI = ‒3.99% to 0.16%) but underestimated mortality among those who had previously received chemotherapy or had a first cancer with more aggressive tumor characteristics. In contrast, Predict overestimated mortality for first estrogen receptor–negative cancers (predicted-observed = 4.54%, 95% CI = 4.27% to 4.86%). Conclusion The Predict tool underestimated 5-year mortality after a second estrogen receptor–positive breast cancer and in certain subgroups of women with a second estrogen receptor–negative breast cancer. [ABSTRACT FROM AUTHOR]

Background Little is known about the microbiology and outcomes of chemotherapy-associated febrile illness among patients in sub-Saharan Africa. Understanding the microbiology of febrile illness could improve antibiotic selection and infection-related outcomes. Methods From September 2019 through June 2022, we prospectively enrolled adult inpatients at the Uganda Cancer Institute who had solid tumors and developed fever within 30 days of receiving chemotherapy. Evaluation included blood cultures, malaria rapid diagnostic tests, and urinary lipoarabinomannan testing for tuberculosis. Serum cryptococcal antigen was evaluated in participants with human immunodeficiency virus (HIV). The primary outcome was the mortality rate 40 days after fever onset, which we estimated using Cox proportional hazards models. Results A total of 104 febrile episodes occurred among 99 participants. Thirty febrile episodes (29%) had ≥1 positive microbiologic result. The most frequently identified causes of infection were tuberculosis (19%) and bacteremia (12%). The prevalence of tuberculosis did not differ by HIV status. The 40-day case fatality ratio was 25%. There was no difference in all-cause mortality based on HIV serostatus, presence of neutropenia, or positive microbiologic results. A universal vital assessment score of >4 was associated with all-cause mortality (hazard ratio, 14.5 [95% confidence interval, 5–42.7]). Conclusions The 40-day mortality rate among Ugandan patients with solid tumors who developed chemotherapy-associated febrile illness was high, and few had an identified source of infection. Tuberculosis and bacterial bloodstream infections were the leading diagnoses associated with fever. Tuberculosis should be included in the differential diagnosis for patients who develop fever after receiving chemotherapy in tuberculosis-endemic settings, regardless of HIV serostatus. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is the most common malignancy among women worldwide. Previous studies have shown factors influencing breast cancer patients' survival, including histopathological grading, stage, histopathological type, hormone receptors, and the number of mitotic images. This study aimed to determine the survival rate in breast cancer patients based on neoadjuvant chemotherapy (NAC) response and regimen. Methods: This was an observational analytic study with a retrospective design. The population was breast cancer patients at our institution who had undergone NAC. Kaplan–Meier analysis using the log-rank method was used to determine the level of survivability (overall survival [OS] and disease-free survival [DFS]) of patients based on chemotherapy response and regimen. Results: The NAC overall response rate of breast cancer patients was 93.17 %, whereas the non-response rate was 6.83 %. Significant differences existed in the DFS of patients by chemotherapy response (p = 0.010). Patients with a complete response had a mean survival of 71.37 ± 2.92 months, those with progressive disease had a mean survival of 64.80 ± 15.58 months, and overall patients had a mean survival of 68.56 ± 10.452 months. Patients with a complete response had a mean recurrence time of 69.54 ± 7.48 months; this was 57.53 ± 19.06 months in those with progressive disease, for an overall time of 65.41 ± 13.81 months. No significant difference existed between the NAC regimens in OS and DFS (p = 0.901 and p = 0.798, respectively). Conclusion: Generally, the response to NAC in breast cancer was very good. The DFS rates were significantly different from the chemotherapy response but not from the NAC regimen.

Cutaneous metastasis of urothelial carcinoma after radical cystectomy is extremely rare. We present the case of a 57-year-old man who underwent a radical cystectomy with ileal conduit for the presence of a bladder tumor. He developed a cheek lesion after 2 months, which was diagnosed as a metastatic nodule along with bone metastases from high-grade bladder urothelial carcinoma. This nodule was treated with surgical removal with subsequent chemotherapy, but he succumbed after 10 months due to widespread metastatic disease. [ABSTRACT FROM AUTHOR]

Simple Summary: To our knowledge, this is the first study that presents a machine learning setup incorporating genetics and clinical factors to predict hearing loss in a large and fairly unique cohort of testicular cancer patients, with follow-up data examining long-range side effects of chemotherapy. Genetic variants in SOD2 and MGST3 are proposed as mechanistically associated with cisplatin-induced hearing loss. Further, the models in this study focus on individual patient benefit and incorporation of quality of life measures to identify hearing loss impact. To study short- and long-term effects of chemotherapy, testicular cancer is ideal as a model disease for other cancers, as patients are young with long life-expectancy and without significant comorbidity. With small adjustments, the model can likely be applied in the treatment of other cancers where cisplatin is used, thus helping with choice of treatment without risking a trade-off in efficacy, standing to influence clinical practice. Testicular cancer is predominantly curable, but the long-term side effects of chemotherapy have a severe impact on life quality. In this research study, we focus on hearing loss as a part of overall chemotherapy-induced ototoxicity. This is a unique approach where we combine clinical data from the acclaimed nationwide Danish Testicular Cancer (DaTeCa)-Late database. Clinical and genetic data on 433 patients were collected from hospital files in October 2014. Hearing loss was classified according to the FACT/GOG-Ntx-11 version 4 self-reported Ntx6. Machine learning models combining a genome-wide association study within a nested cross-validated logistic regression were applied to identify patients at high risk of hearing loss. The model comprising clinical and genetic data identified 67% of the patients with hearing loss; however, this was with a false discovery rate of 49%. For the non-affected patients, the model identified 66% of the patients with a false omission rate of 19%. An area under the receiver operating characteristic (ROC-AUC) curve of 0.73 (95% CI, 0.71–0.74) was obtained, and the model suggests genes SOD2 and MGST3 as important in improving prediction over the clinical-only model with a ROC-AUC of 0.66 (95% CI, 0.65–0.66). Such prediction models may be used to allow earlier detection and prevention of hearing loss. We suggest a possible biological mechanism for cisplatin-induced hearing loss development. On confirmation in larger studies, such models can help balance treatment in clinical practice. [ABSTRACT FROM AUTHOR]

Gastric cancer is the fifth most prevalent cancer worldwide and the third leading cause of cancer- related mortality. Peritoneal carcinomatosis can develop in patients with a primary gastric tumor in a substantial proportion of patients, with estimates ranging from 14% to 43%. For patients with peritoneal carcinomatosis from gastric cancer, therapeutic options are limited. Intraperitoneal chemotherapy, combined with hyperthermia (HIPEC), provides regional dose intensification within the peritoneal cavity, effectively targeting peritoneal carcinomatosis with minimal systemic exposure. We report a case of gastroesophageal junction adenocarcinoma with peritoneal metastasis successfully treated with of cytoreductive surgery and HIPEC, and followed by surgery and systemic chemotherapy, highlighting HIPEC as one of the viable options and the importance of a multimodal approach for the treatment of this case. [ABSTRACT FROM AUTHOR]

Background: Since numerous chemotherapy regimens for the treatment of patients suffering from acute lymphoid leukemia (ALL) have been recently developed, having basic information about the previous results of using the Hyper-CVAD regimen in order to compare with other common chemotherapy regimens is essential. The aim of this study was to evaluate demographic, clinical and outcome of ALL patients receiving Hyper-CVAD regimen. Methods: In this retrospective study, nighty eligible ALL patients treated with the Hyper-CVAD chemotherapy regimen in Omid Hospital, Isfahan, Iran during April 2016 till April 2019 were considered. We evaluated the demographic variables, pathological data and other clinical factors by an information sheet designed by main investigator. The main purpose of this study was to evaluate overall survival, progression-free survival, and overall response rate of patients along with patients’ clinical characteristics and other relevant factors using Kaplan-Meier or Cox-regression and other statistical analyses. Results: The mean overall survival and the median survival of patients were 44.8±2.93 and 36.7±7.47 months; respectively. Also the mean progression free survival of patients was 44.44±3.30 months. More than 84.4% of patients encountered complete remission (CR) after receiving Hyper-CVAD regimen. Reaching to CR had positive significant effects on patients’ overall survival and median survival. However, the bone marrow transplantation variable alone did not affect the patients’ overall survival. The variables such as being B/T Cell ALL, Philadelphia, myeloid marker, and central nervous system involvement did not affect the overall survival of patients but the relapse index indicated the significant effects. The median survival time is higher in patients with no relapse episode. None of the initial lab data had any significant effects on patients’ overall survival. Conclusion: For the first time in Iran, we have obtained the mean survival outcome of ALL patients after applying the Hyper-CVAD regimen. According to the results, the mean overall survival, progression free survival and other survival items in Iranian patients suffering from ALL and receiving Hyper-CVAD regimen were in consistent with previous studies in the world.

Background: This study analyzed data from two consecutive protocols for children newly diagnosed with acute lymphoblastic leukemia (ALL) to determine the clinical impact of minimal/measurable residual disease (MRD) and recently identified tumor genetic subtypes. Methods: Genetic subtypes were determined by sequential approaches including DNA indexing, reverse transcriptase–polymerase chain reaction, multiplex ligation‐dependent probe amplification, and RNA‐sequencing. MRD was assessed by flow cytometry. The Taiwan Pediatric Oncology Group TPOG‐ALL‐2013 study enrolled patients who received MRD‐directed therapy. Results: The 5‐year event‐free survival (EFS) and overall survival rates in the 2013 cohort were 77.8% and 86.9% compared to those of the 2002 cohort, which were 62.4% and 76.5%. Among patients treated with MRD‐guided therapy, those with ETV6‐RUNX1 fusion and high hyperdiploidy had the highest 5‐year EFS (91.4% and 89.6%, respectively). The addition of dasatinib improved outcomes in patients with BCR‐ABL1 ALL. Recently identified subtypes like DUX4‐rearranged, ZNF384‐rearranged, MEF2D‐rearranged, and PAX5alt subtypes were frequently positive for MRD after remission induction, and these patients consequently received intensified chemotherapy. Treatment intensification according to the MRD improved the outcomes of patients presenting DUX4 rearrangements. In high‐risk or very‐high‐risk subtypes, the TPOG‐ALL‐2013 regimen did not confer significant improvements compared to TPOG‐ALL‐2002, and the outcomes of BCR‐ABL1‐like, MEF2D‐rearranged, and KMT2A‐rearranged ALL subtypes (in addition to those of T‐cell ALL) were not sufficiently good. Novel agents or approaches are needed to improve the outcomes for these patients. Conclusions: The TPOG‐ALL‐2013 study yielded outcomes superior to those of patients treated in the preceding TPOG‐ALL‐2002 study. This study provides important data to inform the design of future clinical trials in Taiwan. Plain language summary: MRD‐directed therapy improved the outcomes for pediatric ALL, especially standard‐risk patients.Genomic analyses and MRD might be used together for risk‐directed therapy of childhood ALL.Our work provides important data to inform the design of future clinical trials in Taiwan Genomic analyses and minimal/measurable residual disease together might be the best fit for risk‐directed therapy of childhood acute lymphoblastic leukemia to improve outcomes. [ABSTRACT FROM AUTHOR]

Background: Since numerous chemotherapy regimens for the treatment of patients suffering from acute lymphoid leukemia (ALL) have been recently developed, having basic information about the previous results of using the Hyper-CVAD regimen in order to compare with other common chemotherapy regimens is essential. The aim of this study was to evaluate demographic, clinical and outcome of ALL patients receiving Hyper-CVAD regimen. Methods: In this retrospective study, nighty eligible ALL patients treated with the Hyper-CVAD chemotherapy regimen in Omid Hospital, Isfahan, Iran during April 2016 till April 2019 were considered. We evaluated the demographic variables, pathological data and other clinical factors by an information sheet designed by main investigator. The main purpose of this study was to evaluate overall survival, progression-free survival, and overall response rate of patients along with patients’ clinical characteristics and other relevant factors using Kaplan-Meier or Cox-regression and other statistical analyses. Results: The mean overall survival and the median survival of patients were 44.8±2.93 and 36.7±7.47 months; respectively. Also the mean progression free survival of patients was 44.44±3.30 months. More than 84.4% of patients encountered complete remission (CR) after receiving Hyper-CVAD regimen. Reaching to CR had positive significant effects on patients’ overall survival and median survival. However, the bone marrow transplantation variable alone did not affect the patients’ overall survival. The variables such as being B/T Cell ALL, Philadelphia, myeloid marker, and central nervous system involvement did not affect the overall survival of patients but the relapse index indicated the significant effects. The median survival time is higher in patients with no relapse episode. None of the initial lab data had any significant effects on patients’ overall survival. Conclusion: For the first time in Iran, we have obtained the mean survival outcome of ALL patients after applying the Hyper-CVAD regimen. According to the results, the mean overall survival, progression free survival and other survival items in Iranian patients suffering from ALL and receiving Hyper-CVAD regimen were in consistent with previous studies in the world. [ABSTRACT FROM AUTHOR]

Background and aim: Given the paucity of evidence-based treatment recommendations, the most appropriate first-line regimen for adult Burkitt lymphoma is currently undefined. We aimed to identify the optimal treatment regimen containing rituximab for adult Burkitt lymphoma patients. Methods: The PubMed, Embase, Web of Science, and Cochrane databases were searched in December 2021 (10). We included all studies for the treatment of Burkitt lymphoma including rituximab. We excluded studies of patients aged ≤14 years old and those with sample numbers ≤10 patients. Random-effects models were used to compare different chemotherapy regimens regarding estimated 2-year overall survival (OS) rate, 2-year progression-free survival (PFS) rate, and overall response rate (ORR). Results: A total of 17 studies were included in this meta-analysis and divided into four groups: CODOX-M/IVAC, DA-EPOCH, GMALL-B-ALL/NHL2002, and Hyper-CVAD. DA-EPOCH was associated with a significantly higher 2-year OS rate [0.95, 95% confidence interval (CI) 0.86-1.00]. There was no significant difference in the 2-year PFS rates (0.81, 95% CI 0.76-0.85) and ORR (0.90, 95% CI 0.87-0.94) between these four treatment regimens. Conclusions: The meta-analysis indicates that DA-EPOCH could be more effective in providing curative treatment for adult Burkitt lymphoma patients, especially without CNS and BM involvement considering OS time. Due to the types of studies and the limited number of included studies, bias should be acknowledged and a randomized controlled trial (RCT) needs to be performed to further identify the optimal treatment regimen for such patients. [ABSTRACT FROM AUTHOR]

Hematologic toxicity (HT) during concurrent chemoradiotherapy (CCRT) for cervical cancer can lead to treatment breaks and compromise efficacy. To evaluate the association between severe hematologic toxicity (HT) and clinical factors and pelvic apparent diffusion coefficient (ADC) during CCRT of cervical cancer patients. Data from 120 patients with cervical cancer who were treated with CCRT from January 2016 and December 2018 were retrospectively analyzed. The clinical data (age, menopausal status, clinical stage, body mass index, chemotherapy regimen and chemotherapy cycle) of the patients were collected, and the cohort were divided into two groups based on the HT grade: HT3+ group (HT grade ≥ 3; 66 patients) and HT3- group (HT grade<3; 54 patients). All patients performed MRI before CCRT, and pelvic (ilium, pubis, ischium) ADC value was measured on ADC map. The correlation between severe HT and clinical parameters and pelvic ADC value were analyzed by univariate analysis, and the diagnostic performance was further assessed by receiver operating characteristic (ROC) analysis. In univariate analysis, the menopausal status (p = 0.012) and chemotherapy regimen (p = 0.011) were significantly correlated with severe HT in overall patients, and menopausal patients or patients receiving paclitaxel plus cisplatin (TP) regimen were more likely to develop severe HT. HT3+ group showed a significantly lower pelvic ADC value than HT3- group. The ADC value cut-offs derived from our study for predicting severe HT was 0.317 × 10−3 mm2/s in overall patients. Neither clinical parameters nor pelvic ADCs were associated with severe HT in menopausal patients when analyzed separately (p > 0.05). Severe HT was significantly associated with menopausal status and chemotherapy regimen in patients with cervical cancer treated with CCRT, and HT3+ group showed a lower pelvic ADC value. • Severe HT was associated with menopausal status, chemotherapy regimen and pelvic ADC value in cervical cancer patients. • Patients treated with TP regimen were more likely to develop severe HT. • Menopausal patients with a lower pelvic ADC value were more likely to develop severe HT. [ABSTRACT FROM AUTHOR]

Neoadjuvant chemotherapy (NAC) has shown promising results in patients with locally advanced penile cancer. However, no consensus exists on its applications for locally advanced penile cancer. Thus, it is unclear which kind of chemotherapy regimen is the best choice. Consequently, a systematic search of PubMed, Web of Science, and EMBASE was performed in March 2021 to assess the efficacy and safety of NAC for the treatment of patients with locally advanced penile cancer. The Newcastle–Ottawa Scale was used to assess the risk of bias in each study. This study synthesized 14 published studies. The study revealed that patients who achieved an objective response to NAC obtained a better survival outcome compared with those who did not achieve an objective response. In addition, the objective response rates (ORRs) and pathological complete response (pCR) rates were 0.57 and 0.11, respectively. The incidence of grade ≥3 toxicity was 0.36. Subgroup analysis found that the ORR and pCR of the taxane–platinum (TP) regimen group performed better than those of the nontaxane–platinum (NTP) regimen group (0.57 vs 0.54 and 0.14 vs 0.07, respectively). Moreover, the TP regimen group had more frequent toxicity than the NTP regimen group (0.41 vs 0.26). However, further studies were warranted to confirm the findings.

Testicular cancer is predominantly curable, but the long-term side effects of chemotherapy have a severe impact on life quality. In this research study, we focus on hearing loss as a part of overall chemotherapy-induced ototoxicity. This is a unique approach where we combine clinical data from the acclaimed nationwide Danish Testicular Cancer (DaTeCa)-Late database. Clinical and genetic data on 433 patients were collected from hospital files in October 2014. Hearing loss was classified according to the FACT/GOG-Ntx-11 version 4 self-reported Ntx6. Machine learning models combining a genome-wide association study within a nested cross-validated logistic regression were applied to identify patients at high risk of hearing loss. The model comprising clinical and genetic data identified 67% of the patients with hearing loss; however, this was with a false discovery rate of 49%. For the non-affected patients, the model identified 66% of the patients with a false omission rate of 19%. An area under the receiver operating characteristic (ROC-AUC) curve of 0.73 (95% CI, 0.71–0.74) was obtained, and the model suggests genes SOD2 and MGST3 as important in improving prediction over the clinical-only model with a ROC-AUC of 0.66 (95% CI, 0.65–0.66). Such prediction models may be used to allow earlier detection and prevention of hearing loss. We suggest a possible biological mechanism for cisplatin-induced hearing loss development. On confirmation in larger studies, such models can help balance treatment in clinical practice.

Abstract Relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) has a very poor prognosis with a median overall survival of four to nine months. Achieving a complete molecular response is most often required to obtain a sustained leukemia-free survival after allogeneic hematopoietic stem cell transplantation. Immunotherapies targeting CD19, CD20, or CD22 are very efficient in achieving this goal. However, in the absence of the expression of these immunotherapeutic targets by lymphoblasts, treatment options are extremely scarce. We report the successful treatment of a 26-year-old man who suffered R/R, CD19, CD20, and CD22 negative B-ALL targeting Bcl-2 and CD38 by combining venetoclax and daratumumab with chemotherapy.

Background: Breast cancer (BC) is the second leading cause of tumor-related mortality after lung cancer. Chemotherapy resistance remains a major challenge to progress in BC treatment, warranting further exploration of feasible and effective alternative therapies., Aim: To analyzed the quality of life (QoL) and survival of patients with BC treated with integrated traditional Chinese and Western medicine (TCM-WM)., Methods: This study included 226 patients with BC admitted to the First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine between February 2018 and February 2023, including 100 who received conventional Western medicine treatment (control group) and 126 who received TCM-WM treatment (research group). The total effective rate, side effects (alopecia, nausea and vomiting, hepatorenal toxicity, and myelosuppression), QoL assessed using the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30), 1-year overall survival (OS), recurrence and metastasis rates, and serum inflammatory factors [interleukin (IL)-6, IL-10, and tumor necrosis factor alpha] were comparatively analyzed., Results: The research group showed statistically better overall efficacy, EORTC QoL-C30 scores, and 1-year OS than the control group, with markedly lower side effects and 1-year recurrence and metastasis rates. Moreover, the posttreatment levels of serum inflammatory in the research group were significantly lower than the baseline and those in the control group., Conclusion: Overall, TCM-WM demonstrated significantly improved therapeutic efficacy while ensuring drug safety in BC, which not only improved patients' QoL and prolonged survival, but also significantly inhibited the inflammatory response., Competing Interests: Conflict-of-interest statement: There is no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)