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Background: Multimodal therapies, such as perioperative chemotherapy and neoadjuvant chemoradiotherapy together with surgical advances, have improved the outcomes of patients with resectableesophageal cancer (EC).However, the 5-year survival of these patients remains below 50%. The advent of immunotherapy has resulted in novel approaches to advanced or metastatic disease, but the role of immunotherapy in the neoadjuvant settings has not yet to be established. In this single-arm study, the efficacy and safetyofneoadjuvant pembrolizumab plus chemotherapy were evaluatedin patients with resectableesophageal squamous cell carcinoma (ESCC).Methods: This study was conducted at 2 hospitals(in Xi'an and Tianjin)and included patients with ESCC of clinical stage II–IVAwho underwent surgery within 4 to 6 weeks after completing treatment withpembrolizumab(200mg) combined with a conventional chemotherapy regimen (3 cycles). The efficacy and safety of this combination treatment were evaluated as primary endpointsof the study. This study was retrospectively registered (Registration number: ChiCTR2100048917).Results:A total of 22 patients (including 18 men) were enrolled, of whom 17 patients progressed to surgery,4 patients refused surgery due to tumor regression and symptomatic relief, and 1 patient had progressive disease. As determinedby the Response Evaluation Criteria in Solid Tumors(RECIST,version 1.1), 7 patients (31.8%) had a partial response and 4 (18.2%) patients hada complete response, which translated to an objective response rate of 50%. The symptom remission rate was 90.9% according to the Stooler classification. Five patients (22.7%) experienced serious treatment-related adverse events of grade 3–4 (including anorexia, vomiting, fatigue, alopecia and hypoadrenalism). Postoperative pathology revealed a major pathological response in 14 cases (82.3%) and a complete pathological response in 8 cases (47.1%). Programmed death-ligand 1expression in pretreatment specimens was not significantly associated with the percentage of residual viable tumor (RVT)(r=-0.55, p=0.08). Changes in counts of CD68+ macrophage between pre- and post-treatment specimens wereweakly correlated with RVT(r=0.71; p=0.07), while a positive correlation was observed between postoperative Foxp3+T cells/CD4+Tcellsratios and RVT(r=0.84, p=0.03).Conclusion: The combination of neoadjuvantimmunotherapy and chemotherapy for ESCC is associated with a high pathological response and immunologic effects in the tumor microenvironment. It has acceptable toxicity and great efficacy, suggesting a strong rationale for its further evaluation in randomized clinical trials.Trial registration: ChiCTR, ChiCTR2100048917. Registered 19 July 2021 - Retrospectively registered, https://www.chictr.org.cn/edit.aspx?pid=130073&htm=4

Background: Neoadjuvant chemoradiation (NeoCRT) is standard of care for the treatment of locally advanced rectal cancer (LARC). Contemporary radiation techniques and pre-treatment imaging may impact toxicities and pathologic response (PR). Herein we compare intensity modulated radiotherapy (IMRT) and advanced pre-treatment imaging in the neoadjuvant treatment of LARC and resulting impact on toxicities and pathologic outcomes relative to 3 dimensional conformal radiotherapy (3DCRT). Methods: LARC patients treated at 4 large academic centers in the US from 2007–2016 were reviewed. Patients received 5-FU-based NeoCRT concurrently with IMRT or 3DCRT. PR was recorded as none, partial, or complete. Common terminology for adverse events version 4 was used to grade toxicities. Toxicity rates were compared using Chi-square analysis. Multivariable models were fit adjusting for age, gender, pre-tx CT to identify independent predictors of PR and toxicity. Results: A total of 128 patients were analyzed: 60.1% male and 39.8% female, median age 57.7 years (range, 31–85 years). Clinical characteristics were similar across RT groups. The outcome of partial and complete PR was similar for IMRT and 3DCRT (48.1%, 23.1% vs. 31.7%, 23.3%), respectively. After adjusting for gender, age, and pre-RT chemotherapy type, IMRT and pretreatment PET and/or MRI imaging was significantly associated with increased odds for complete and partial response (OR =2.95, 95% CI: 1.21–7.25, P=0.018; OR =14.70, 95% CI: 3.69–58.78, P

To identify clinical parameters that are prognostic for improved overall survival (OS) after yttrium-90 radioembolization (RE) in patients with liver metastases from colorectal cancer (CRC).A total of 131 patients who underwent RE for liver metastases from CRC, treated at 2 academic centers, were reviewed. Twenty-one baseline pretreatment clinical factors were analyzed in relation to OS by the Kaplan-Meier method along with log-rank tests and univariate and multivariate Cox regression analyses.The median OS from first RE procedure was 10.7 months (95% confidence interval [CI], 9.4-12.7 months). Several pretreatment factors, including lower carcinoembryonic antigen (CEA; ≤20 ng/mL), lower aspartate transaminase (AST; ≤40 IU/L), neutrophil-lymphocyte ratio (NLR)5, and absence of extrahepatic disease at baseline were associated with significantly improved OS after RE, compared with high CEA (20 ng/mL), high AST (40 IU/L), NLR ≥5, and extrahepatic metastases (P values of.001,.001, .0001, and .04, respectively). On multivariate analysis, higher CEA, higher AST, NLR ≥5, extrahepatic disease, and larger volume of liver metastases remained independently associated with risk of death (hazard ratios of 1.63, 2.06, 2.22, 1.48, and 1.02, respectively).The prognosis of patients with metastases from CRC is impacted by a complex set of clinical parameters. This analysis of pretreatment factors identified lower AST, lower CEA, lower NLR, and lower tumor burden (intra- or extrahepatic) to be independently associated with higher survival after hepatic RE. Optimal selection of patients with CRC liver metastases may improve survival rates after administration of yttrium-90.

Background: This study seeks to quantify and compare bone marrow tolerance during postoperative chemotherapy therapy between rectal cancer vs. colon cancer patients. During rectal cancer treatment, patients receive neoadjuvant chemoradiation (CRT) irradiation which can exacerbate the hematologic toxicity (HT) via incidental irradiation of the pelvic bone marrow (PBM) during myelosuppressive postoperative chemotherapy. In contrast, colon cancer patients receive the same postoperative myelosuppressive chemotherapy but do not routinely receive preoperative chemoradiation therapy. This comparison will help elucidate the lasting myelosuppressive effects of incidental pelvic bone marrow (PBM) irradiation on rectal cancer patients during neoadjuvant preoperative chemoradiation therapy. Methods: Rectal cancer patients treated with preoperative CRT followed by postoperative 5-Fluorouracil and oxaliplatin (OxF) chemotherapy (n=35) were compared to colon cancer patients who received only postoperative OxF chemotherapy (n=42). End points were ≥ grade 3 hematologic toxicity (HT3) or hematologic event (HE) defined as ≥ grade 2 HT and a dose reduction in OxF. Wilcoxon rank sum test tested continuous variables and Chi-squared test measured differences in categorical variables. HT3 and HE probability during postoperative chemotherapy was estimated with Kaplan-Meier curves and Cox regression analysis. Results: During OxF chemotherapy, 40.0% (n=14) of rectal cancer patients experienced HT3 compared to 26.1% (n=11) of colon cancer patients (P=0.4). HE was experienced by 48% (n=17) of rectal cancer patients compared to 36% (n=15) of colon cancer patients (P=0.36). Rectal cancer patients were likelier to experience HT3 on multivariable cox regression analysis, controlling for several clinical covariates, with a hazard ratio (HR) of 2.49, [(95% CI: 1.02–6.02), P=0.045] than colon cancer patients. While rectal cancer patients were more likely to experience HE than colon cancer patients on multivariable Cox regression analysis with a HR of 1.8 (95% CI: 0.95–3.75), this only trended in statistical significance, P=0.07. Conclusions: Rectal cancer patients are more likely than colon cancer patients to experience hematologic toxicities impacting the tolerance of standard of care chemotherapeutics during adjuvant therapy. Focused PBM sparing during radiation therapy for rectal cancer patients may improve tolerance of myelosuppressive chemotherapeutic agents delivered in the postoperative setting.

Background Hepatocellular carcinoma (HCC) in non-cirrhotic livers is an uncommon finding and can present insidiously in patients. Another uncommon finding in HCC, and one of poor prognosis, is the presence of paraneoplastic diseases such as hypercalcemia. We report a case of a 66-year-old previous healthy Filipina woman who after routine laboratory evaluation was discovered to have hypercalcemia as the first sign of an advanced HCC without underlying cirrhosis. Because of the patient's relative lack of symptoms, healthy liver function, lack of classical HCC risk factors, and unexpected hypercalcemia, the diagnosis of a paraneoplastic syndrome caused by a noncirrhotic HCC was unanticipated. Methods Case Analysis with Pubmed literature review. Results It is unknown how often hypercalcemia is found in association with HCC in a non-cirrhotic liver. However, paraneoplastic manifestations of HCC, particularly hypercalcemia, can be correlated with poor prognosis. For this patient, initial management included attempts to lower calcium levels via zoledronate, which wasn't completely effective. Tumor resection was then attempted however the patient expired due to complications from advanced tumor size. Conclusions Hypercalcemia of malignancy can be found in association with non-cirrhotic HCC and should be considered on the differential diagnosis during clinical work-up.

Multiple myeloma (MM) rarely presents with a primary neurological dysfunction, and if it does it is usually due to a plasmacytoma. This is the first case to discuss hypoglossal nerve dysfunction as the first sign of MM progression secondary to severe pathophysiologic bone lysis. A PubMed-based literature search was completed on April 17, 2016 for the terms “multiple myeloma” and “hypoglossal nerve neuropathy”. A 73-year-old woman with known MM who received little treatment for several years, presented secondary to dysarthria and at first was thought to have hyperviscosity syndrome. On further examination, it was found she had light chain disease and her symptoms were secondary to severe disease progression. Imaging revealed multiple lytic lesions in the skull on skeletal survey and brain MRI revealed boney lysis near the occipital condyle and clivus likely interfering with the coursing of the hypoglossal nerve. Advanced progressing MM can cause severe boney destruction which can interfere with cranial nerve canals and cause neuropathy as a presenting symptom.

Background In the present study, we assessed the effect of prostate gland size on patient-assessed genitourinary and gastrointestinal (GI) quality of life (QOL) after definitive treatment of prostate adenocarcinoma with proton beam therapy. Patients and Methods As a part of a prospective outcome tracking protocol, 81 patients treated at a single center between with proton beam therapy completed the Expanded Prostate Cancer Index Composite (EPIC) questionnaire before treatment and at the follow-up examinations. We reviewed the dosimetric data, reported as V x (volume of organ receiving x Gy), and patient-reported QOL at 6 months. Genitourinary QOL was assessed using the American Urological Association symptom score and EPIC urinary domain score. GI QOL was assessed using the EPIC GI domain score. Results Larger prostate glands were associated with greater bladder V 70 ( P 70 ( P 70 was 95%) maintained. Patients with larger prostates did not have a greater change in their American Urological Association symptom index scores ( 3 , +2.3; 30-49 cm 3 , +3.2; ≥ 50 cm 3 , 0.2; P = .06) or urinary domain score ( 3 , −3.6; 30-49 cm 3 , −3.1; ≥ 50 cm 3 , +3.8; P = .76) at 6 months after treatment. Also, prostate size was not associated with a change in the EPIC GI domain score at 6 months after treatment ( 3 , −3.7; 30-49 cm 3 , −1.1; ≥ 50 cm 3 , −0.55; P = .67). Conclusion Definitive proton beam therapy for prostate cancer to a dose of 79.2 Gy resulted in excellent patient-reported urinary and GI QOL, independently of the baseline prostate size. This single-institution finding should be tested further in a multi-institutional study to confirm the potential limited role of androgen deprivation therapy.

Purpose/Objective(s) To quantify ensuing bone marrow (BM) suppression during postoperative chemotherapy resulting from preoperative chemoradiation (CRT) therapy for rectal cancer. Methods and Materials We retrospectively evaluated 35 patients treated with preoperative CRT followed by postoperative 5-Fluorouracil and oxaliplatin (OxF) chemotherapy for locally advanced rectal cancer. The pelvic bone marrow (PBM) was divided into ilium (IBM), lower pelvis (LPBM), and lumbosacrum (LSBM). Dose volume histograms (DVH) measured the mean doses and percentage of BM volume receiving between 5-40 Gy (i.e.: PBM-V5, LPBM-V5). The Wilcoxon signed rank tests evaluated the differences in absolute hematologic nadirs during neoadjuvant vs. adjuvant treatment. Logistic regressions evaluated the association between dosimetric parameters and ≥ grade 3 hematologic toxicity (HT3) and hematologic event (HE) defined as ≥ grade 2 HT and a dose reduction in OxF. Receiver Operator Characteristic (ROC) curves were constructed to determine optimal threshold values leading to HT3. Results During OxF chemotherapy, 40.0% (n=14) and 48% (n=17) of rectal cancer patients experienced HT3 and HE, respectively. On multivariable logistic regression, increasing pelvic mean dose (PMD) and lower pelvis mean dose (LPMD) along with increasing PBM-V (25-40), LPBM-V25, and LPBM-V40 were significantly associated with HT3 and/or HE during postoperative chemotherapy. Exceeding ≥36.6 Gy to the PMD and ≥32.6 Gy to the LPMD strongly correlated with causing HT3 during postoperative chemotherapy. Conclusions Neoadjuvant RT for rectal cancer has lasting effects on the pelvic BM, which are demonstrable during adjuvant OxF. Sparing of the BM during preoperative CRT can aid in reducing significant hematologic adverse events and aid in tolerance of postoperative chemotherapy.

Capgras delusion (CD) has multiple etiologies including neurodegenerative disorders and can be associated with violent behavior. CD is a common complication of Alzheimer dementia (AD); however, CD with violent behavior is uncommon in AD. We report escalating violent behavior by a patient with advanced AD and CD who presented to the emergency department (ED) and required admission to an academic medical center.Case analysis with PubMed literature review.A 75-year-old male with a 13-year history of progressive AD, asymptomatic bipolar disorder, chronic kidney disease, hypertension, hyperlipidemia, and benign prostatic hypertrophy presented to the ED with recurrent/escalating violence toward his wife, whom he considered an impostor. His psychotropic regimen included potentially inappropriate medications (PIMs) for geriatric/AD patients-topiramate/amitriptyline/chlordiazepoxide/olanzapine-that are associated with delirium, cognitive decline, dementia, and mortality. Renal dosing for topiramate, reduction in PIMs/anticholinergic burden, and substituting haloperidol for olanzapine resolved his violent behavior and CD.CD in AD is a risk factor for violent behavior. As the geriatric population in the United States grows, CD in patients with AD may present more frequently in the ED, requiring proper treatment. Pharmacovigilance is necessary to minimize PIMs in geriatric/AD patients. Clinicians and other caregivers require further education to appropriately address CD in AD.