Long-Term Survival of Patients With Cancer, Sepsis, and Vasopressor Requirements Based on Lactate Levels.

A prospective cohort study was conducted to evaluate the 1-year survival of cancer patients with sepsis and vasopressor requirements. Eligible patients were admitted a Comprehensive Cancer Center's ICU and were compared based on their admission lactate levels. Of the 132 included patients, 87 (66%) had high lactate (HL; > 2.0 mmol/L), and 45 (34%) had normal lactate (NL; ≤ 2.0 mmol/L). The 1-year survival rates of the two groups were similar (HL 16% vs. NL 18%; p = 0.0921). After adjustment for ICU baseline characteristics, HL was not significantly associated with a 1-year survival (Hazards ratio, 1.39; 95% CI, 0.94-2.05). Critically ill cancer patients with sepsis and vasopressor requirements, regardless of the lactate level, had 1-year survival of less than 20%. Large multicenter cancer registries would enable to confirm our findings and better understand the long-term trajectories of sepsis in this vulnerable population.

Biochemical Safety of SBRT to Multiple Intrahepatic Lesions for Hepatocellular Carcinoma.

Background: We aim to better characterize stereotactic body radiation therapy (SBRT)-related hepatic biochemical toxicity in patients with multiple intrahepatic lesions from hepatocellular carcinoma (HCC). Methods: We conducted a retrospective analysis of patients with HCC who underwent SBRT for 2 or more synchronous or metachronous liver lesions. We collected patient characteristics and dosimetric data (mean liver dose [MLD], cumulative effective volume [Veff], cumulative volume of liver receiving 15 Gy [V15Gy], and cumulative planning target volume [PTV]) along with liver-related toxicity (measured by albumin-bilirubin [ALBI] and Child-Pugh [CP] scores). A linear mixed-effects model was used to assess the effect of multi-target SBRT on changes in ALBI. Results: There were 25 patients and 56 lesions with median follow-up of 29 months. Eleven patients had synchronous lesions, and 14 had recurrent lesions treated with separate SBRT courses. Among those receiving multiple SBRT courses, there were 7 lesions with overlap of V15Gy (median V15Gy overlap: 35 mL, range: 0.5-388 mL). There was no association between cumulative MLD, Veff, V15Gy, or PTV and change in ALBI. Four of 25 patients experienced non-classic radiation-induced liver disease (RILD), due to an increase of CP score by ≥2 points 3 to 6 months after SBRT. Sixteen of 25 patients experienced an increase in ALBI grade by 1 or more points 3 to 6 months after SBRT. Comparing the groups that received SBRT in a single course versus multiple courses revealed no statistically significant differences in liver toxicity. Conclusion: Liver SBRT for multiple lesions in a single or in separate courses is feasible and with acceptable risk of hepatotoxicity. Prospective studies with a larger cohort are needed to better characterize safety in this population.

Prospective Characterization of Circulating Tumor Cell Kinetics in Patients With Oligometastatic Disease Receiving Definitive Intent Radiation Therapy.

PURPOSE: There are currently no predictive molecular biomarkers to identify patients with oligometastatic disease (OMD) who will benefit from definitive-intent radiation therapy (RT). We prospectively characterized circulating tumor cell (CTC) kinetics in patients with OMD undergoing definitive-intent RT. METHODS: This prospective correlative biomarker study included patients with any solid malignancy ≤5 metastatic sites in ≤3 anatomic organ systems undergoing definitive-intent RT to all disease sites. Circulating tumor cells (CTCs) were captured and enumerated using a biomimetic cell rolling and nanotechnology-based assay functionalized with antibodies against epithelial cell adhesion molecule, against human epidermal growth factor receptor 2, and against epidermal growth factor receptor before and during RT and at follow-up visits up to 2 years post-RT. RESULTS: We enrolled 43 patients with a median follow-up of 14.3 months. The pretreatment CTC level (cells captured/mL) was not associated with the number of disease sites (median one metastatic site/patient, range 1-5) or metastasis location (bone, brain, visceral) on Wilcoxon signed-rank test, P > .05. Post-RT, 56% of patients received systemic therapy, and 72% of patients experienced subsequent local or systemic progression. For 90% of patients, a CTC level <15 within 130 days post-RT corresponded to a durable control of irradiated lesions. Patients with a favorable versus an unfavorable clearance profile experienced significantly longer progression-free survival after RT (median 13 v 4 months, log-rank test, P = .0011). On logistic regression, CTC level >15 at a given time point was associated with clinical disease progression within the subsequent 6 months (odds ratio 3.31, P = .007). In 26% of patients with disease progression, a CTC level >15 preceded radiographic or clinical progression. CONCLUSION: CTCs may serve as a biomarker for disease control in OMD and may predict disease progression before standard assessments for patients receiving diverse cancer-directed therapies.

Changes in serum prealbumin as a marker for nitrogen balance in surgical oncology patients.

BACKGROUND: Serum prealbumin has long been used as a marker of nutritional status. However, prealbumin is a negative acute phase reactant influenced by several non-nutritional-related factors including surgery, infection, and cancer. An increasing prealbumin has been correlated with a positive nitrogen balance in general surgery patients receiving parenteral nutrition (PN) with 88% specificity and 70% sensitivity. To date, no trial has evaluated the effect of concurrent cancer and surgery on the value of prealbumin in predicting nitrogen balance. METHODS: This study is a concurrent retrospective design of post-operative patients (≥ 19 years of age) identified by the nutrition support service who received PN for ≥ 5 days, had a baseline and follow-up serum prealbumin and C-reactive Protein (CRP) measured, as well as a 24-h urinary urea nitrogen (UUN) performed between days 5-10 of PN. Exclusion criteria include anuric renal failure, Child-Pugh Class C liver failure, pregnancy, and corticosteroid use. Prealbumin was correlated to nitrogen balance, measuring sensitivity, specificity, and negative and positive predictive values. Information was collected regarding patient demographics and presence or absence of metastatic cancer. RESULTS: Thirty patients were identified and evaluated for this study from December 1st, 2010 to July 15th, 2011. Patients included in the study had a mean age of 57 years old (range 20-82), 53% male, with a mean weight of 84 kg (range 42-140) and body mass index (BMI) of 29 kg/m2 (range 14.9-56.8). The mean daily caloric dose of PN per actual body weight was 21 kcal/kg (range 10-34) and the mean daily protein dose was 1.4 g/kg (range 1-2). Forty seven percent of patients were obese (BMI > 30 kg/m2) and were prescribed high-protein hypocaloric PN. The most common indication for PN was post-operative ileus (23/30 patients). 24-h urine collection for UUN was performed on average of day 8 after PN initiation (range 5-10 days). Nitrogen balance as calculated from 24-h UUN was positive in 17/30 patients. A positive prealbumin change of greater than 2.8 mg/dL was found to have a statistically significant association with positive nitrogen balance (p = 0.02). At the cut off level of positive 2.8 mg/dL, the likelihood of a positive nitrogen balance had a sensitivity of 82% (95% confidence interval (CI) 64-100%); specificity of 62% (95% CI 35-88%); positive predictive value of 74% (95% CI 54-93%); negative predictive value of 73% (95% CI 46-99%). No absolute value for prealbumin level (e.g., > 20  mg/dL) was found to be a significant predictor of positive nitrogen balance. CRP levels at initiation of PN were significantly elevated with a mean level of 147 mg/dL. CONCLUSION: These results indicate a positive change in serum prealbumin (> 2.8 mg/dL) has sufficient sensitivity (82%) to predict positive changes in nitrogen balance in the surgical oncology population. However, the low specificity (62%) makes it less useful in predicting a negative nitrogen balance. Absolute prealbumin levels were greatly affected by inflammation, as evidenced by CRP levels, and single values were not useful in predicting positive nitrogen balance. CLINICAL RELEVANCY: Positive changes in serum prealbumin levels have previously been associated with a positive nitrogen balance (NB) in surgical patients receiving parenteral nutrition (PN); however, it is unclear if this is true in oncologic surgery patients. This study highlights how changing levels of serum prealbumin and C-reactive protein correlates to NB for cancer patients in the post-operative period requiring PN. Changes in prealbumin levels from baseline showed sufficient sensitivity, but not specificity to utilize routinely for predicting NB in this population.

Factors associated with radiation necrosis and intracranial control in patients treated with immune checkpoint inhibitors and stereotactic radiotherapy.

BACKGROUND AND PURPOSE: Emerging data suggest immune checkpoint inhibitors (ICI) and stereotactic radiosurgery (SRS) or radiotherapy (SRT) may work synergistically, potentially increasing both efficacy and toxicity. This manuscript characterizes factors associated with intracranial control and radiation necrosis in this group. MATERIALS AND METHODS: All patients had non-small cell lung cancer, renal cell carcinoma, or melanoma and were treated from 2013 to 2021 at two institutions with ICI and SRS/SRT. Univariate and multivariate analysis were used to analyze factors associated with local failure (LF) and grade 2+ (G2 + ) radiation necrosis. RESULTS: There were 179 patients with 549 metastases. The median follow up from SRS/SRT was 14.7 months and the median tumor size was 7 mm (46 tumors ≥ 20 mm). Rates of LF and G2 + radiation necrosis per metastasis were 5.8% (32/549) and 6.9% (38/549), respectively. LF rates for ICI +/- 1 month from time of radiation versus not were 3% (8/264) and 8% (24/285) (p = 0.01), respectively. G2 + radiation necrosis rates for PD-L1 ≥ 50% versus < 50% were 17% (11/65) and 3% (5/203) (p=<0.001), respectively. PD-L1 ≥ 50% remained significantly associated with G2 + radiation necrosis on multivariate analysis (p = 0.03). Rates of intracranial failure were 54% (80/147) and 17% (4/23) (p = 0.001) for those without and with G2 + radiation necrosis, respectively. CONCLUSIONS: PD-L1 expression (≥50%) may be associated with higher rates of G2 + radiation necrosis, and there may be improved intracranial control following the development of radiation necrosis. Administration of ICIs with SRS/SRT is overall safe, and there may be some local control benefit to delivering these concurrently.

Outcomes of surgical resection and intraoperative electron radiotherapy for patients with para-aortic recurrences of gastrointestinal and gynecologic malignancies.

BACKGROUND: Para-aortic lymph node (PALN) metastases from primary pelvic malignancies are often treated with resection, but recurrence is common. We report toxicity and oncologic outcomes for patients with PALN metastases from gastrointestinal and gynecologic malignancies treated with resection and intraoperative electron radiotherapy (IORT). METHODS: We retrospectively identified patients with recurrent PALN metastases who underwent resection with IORT. All patients were included in the local recurrence (LR) and toxicity analyses. Only patients with primary colorectal tumors were included in the survival analysis. RESULTS: There were 26 patients with a median follow up of 10.4 months. The rate of para-aortic local control (LC) was 77% (20/26 patients) and the rate of any cancer recurrence was 58% (15/26 patients). Median time from surgery and IORT to any recurrence was 7 months. The LR rate for those with positive/close margins was 58% (7/12 patients) versus 7% (1/14 patients) for those with negative margins (p = 0.009). 15% (4/26 patients) developed surgical wound and/or infectious complications, 8% (2/26 patients) developed lower extremity edema, 8% (2/26 patients) experienced diarrhea, and 19% (5/26 patients) developed an acute kidney injury. There were no reported nerve injuries, bowel perforations, or bowel obstructions. For patients with primary colorectal tumors (n = 19), the median survival (OS) was 23 months. CONCLUSIONS: We report favorable LC and acceptable toxicity for patients receiving surgical resection and IORT for a population that has historically poor outcomes. Our data show disease control rates similar to literature comparisons for patients with strong risk factors for LR, such as positive/close margins.

A Diagnostic Dilemma: Atypical Systemic Pyoderma Gangrenosum.

Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis that classically presents with chronic ulcerations with raised, violaceous, and undermined borders commonly found on the lower extremities. Less common presentations include tender nodules, pustules, or bullae that may occur on other sites of the body. In rarer circumstances, PG can lead to a systemic inflammatory response syndrome with extensive pulmonary infiltrates but ultimately cause and etiology of the disease are still uncertain. Unfortunately, there is no laboratory test or histopathologic finding that is specific to PG, which makes the diagnosis even more elusive.

Illusory Responses across the Lewy Body Disease Spectrum.

OBJECTIVE: This study was undertaken to study pareidolias, or perceived meaningful objects in a meaningless stimulus, in patients across the Lewy body (LB) disease spectrum, where most do not report hallucinations or delusions. METHODS: We studied illusory responses on the Noise Pareidolia Task in 300 participants (38 cognitively impaired LB, 65 cognitively unimpaired LB, 51 Alzheimer disease spectrum [AD-s], 146 controls). Pairwise between-group comparisons examined how diagnosis impacts the number of illusory responses. Ordinal regression analysis compared the number of illusory responses across diagnosis groups, adjusting for age, sex, and education. Analyses were repeated after removing participants with reported hallucinations or delusions. RESULTS: Cognitively impaired LB participants were 12.3, 4.9, and 4.6 times more likely than control, cognitively unimpaired LB, and AD-s participants, respectively, to endorse illusory responses. After adjusting for age, sex, and education, the probability of endorsing 1 or more illusory responses was 61% in the cognitively impaired LB group, compared to 26% in AD-s, 25% in cognitively unimpaired LB, and 12% in control participants. All results were similar after repeated analysis only in participants without hallucinations or delusions. In LB without hallucinations or delusions, 52% with mild cognitive impairment and 66.7% with dementia endorsed at least 1 illusory response. INTERPRETATION: We found illusory responses are common in cognitively impaired LB patients, including those without any reported psychosis. Our data suggest that, prior to the onset of hallucinations and delusions, the Noise Pareidolia Task can easily be used to screen for unobtrusive pareidolias in all LB patients. ANN NEUROL 2023;93:702-714.

Malignant myopericytoma: Case report and review of the literature.

A 29-year-old male presented with a two-week history of a tender lesion on his right thigh. The lesion was a 1.5 cm erythematous nodule with overlying hemorrhagic crust. Histopathologic examination of a biopsy specimen revealed a highly cellular neoplasm with irregular vesicular nuclei, prominent nucleoli, and scattered mitotic figures. The cells within the lesion were rounded, ovoid and spindle shaped cells with perivascular growth. The architecture and staining pattern of the lesion were most consistent with a diagnosis of malignant myopericytoma, an exceedingly rare malignancy.

Treatment of Localized Amyloid Light Chain Amyloidosis With External Beam Radiation Therapy.

PURPOSE: Localized amyloidosis is a condition characterized by deposits of fibrillary proteins confined to a single organ. The most common subtype is amyloid light chain amyloidosis, which is caused by secretion of amyloidogenic light chain by a monoclonal population of plasma cells. We present a review and discussion of the literature in the context of a case presentation of localized amyloid light chain amyloidosis of the nasopharynx treated with radiation alone. METHODS AND MATERIALS: We reviewed literature relevant to this topic from 1970 to the present. Relevant studies, reports, and articles were summarized in table form. RESULTS: Surgical resection has historically been the primary therapeutic modality for these patients, with radiation being reserved for recurrent lesions or for those unfit for surgery. Although the data are limited to small retrospective series, radiation has been shown to provide good control with mild toxicity that is as good as or better than surgery. Doses range from 20 to 45 Gy, conventionally fractionated. There is no known risk of progression to systemic disease without local therapy. CONCLUSIONS: We recommend local therapy for symptomatic patients after systemic disease has been excluded. We generally recommend radiation in the setting of recurrent lesions, unacceptable toxicity with surgery, poor surgical candidates, and as the initial modality in select patients (elderly individuals with bothersome but nonobstructive lesions).

Integrating de novo and inherited variants in 42,607 autism cases identifies mutations in new moderate-risk genes.

To capture the full spectrum of genetic risk for autism, we performed a two-stage analysis of rare de novo and inherited coding variants in 42,607 autism cases, including 35,130 new cases recruited online by SPARK. We identified 60 genes with exome-wide significance (P < 2.5 × 10-6), including five new risk genes (NAV3, ITSN1, MARK2, SCAF1 and HNRNPUL2). The association of NAV3 with autism risk is primarily driven by rare inherited loss-of-function (LoF) variants, with an estimated relative risk of 4, consistent with moderate effect. Autistic individuals with LoF variants in the four moderate-risk genes (NAV3, ITSN1, SCAF1 and HNRNPUL2; n = 95) have less cognitive impairment than 129 autistic individuals with LoF variants in highly penetrant genes (CHD8, SCN2A, ADNP, FOXP1 and SHANK3) (59% vs 88%, P = 1.9 × 10-6). Power calculations suggest that much larger numbers of autism cases are needed to identify additional moderate-risk genes.

Transarterial Chemoembolization with LC Bead LUMI followed by Stereotactic Body Radiation Therapy in Treatment of Hepatocellular Carcinoma.

PURPOSE: Transarterial chemoembolization (TACE) in combination with stereotactic body radiation therapy (SBRT) is a promising therapy for patients with hepatocellular carcinoma (HCC). A radiopaque drug-eluting embolic bead used during TACE, called LC Bead LUMI (Boston Scientific), was developed to allow improved visualization during TACE. The purpose of this case series is to assess the visibility of LUMI after TACE and discuss its potential use as an alignment tool for SBRT. METHODS: Fourteen patients with HCC (median age 69) received TACE using LUMI immediately followed by SBRT to 50 Gy in 5 fractions (13 patients) or 40 Gy in 5 fractions (1). Computed tomography (CT) simulation and cone beam CT (CBCT) images taken before each fraction were compared with immediate post-TACE imaging. Success of the LUMI bead opacification was graded from excellent to poor visualization. Patients were followed to assess target lesion response, disease control, survival, and the long-term visibility of LUMI beads. RESULTS: CBCT immediately after TACE with LUMI displayed excellent tumor visibility for 6 of 13 patients (46.2%), moderate tumor visibility for 4 patients (30.8%), and poor tumor visibility for 3 patients (23.1%). When comparing CBCTs used for SBRT image verification to post-TACE CBCT, 53.8% remained unchanged and 46.2% deteriorated from excellent to moderate or moderate to poor, but none deteriorated from excellent to poor visualization. Median follow-up was 13 months (range 2-35). On average, LUMI beads were visible on noncontrast CT up to 20 months after SBRT. CONCLUSIONS: LC Bead LUMI has the ability to provide liver tumor demarcation on noncontrast and cone beam CT weeks to months following TACE. It can serve as an alignment tool and could improve the therapeutic ratio in liver SBRT by allowing for tumor margin reduction with a potential decrease in the risk of toxicity when treating HCC in facilities without magnetic resonance imaging-linear accelerator.

Confirming Pathogenicity of the F386L PSEN1 Variant in a South Asian Family With Early-Onset Alzheimer Disease.

OBJECTIVES: The F386L PSEN1 variant has been reported in 1 Japanese family with limited clinical information. We aimed to prove that F386L is pathogenic by demonstrating that it segregates with early-onset Alzheimer disease (AD). METHODS: Eight individuals in a South Asian family provided DNA for genetic testing and underwent a neurologic examination. RESULTS: The female proband was diagnosed with AD at age 45 years and died at age 49 years. She had a CSF biomarker profile consistent with AD, and her florbetaben PET scan was amyloid positive with high uptake in the striatum. Her MRI showed no prominent white matter disease. Her affected relatives had an age at onset range of 38-57 years and had imaging and biomarker profiles similar to hers. DISCUSSION: The results presented here, in conjunction with the prior report, confirm the pathogenicity of F386L. Furthermore, our study highlights the importance of studying families from underrepresented populations to identify or confirm the pathogenicity of rare variants that may be specific to certain genetic ancestries.

Dosimetric and Clinical Factors Associated With Breast Reconstruction Complications in Patients Receiving Postmastectomy Radiation.

PURPOSE: Approximately 30% of women who receive postmastectomy radiation therapy in the setting of breast reconstruction suffer from reconstruction complications. This study aims to assess clinical and dosimetric factors associated with the risk of reconstruction complications after postmastectomy radiation therapy, with the ultimate goal of identifying a dosimetric constraint that can be used clinically to limit this risk. METHODS AND MATERIALS: We retrospectively identified 41 patients who underwent a modified radical or total mastectomy, followed by immediate or delayed reconstruction (autologous or implant-based) and radiation at a single institution between 2014 and 2020. Reconstruction complications were defined as a flap or implant failure, necrosis, capsular contracture, cellulitis/infection, implant rupture, implant malposition, leakage/rupture, unplanned operation, and hematoma/seroma. Clinical and dosimetric variables associated with complications were assessed with univariate analyses. RESULTS: Twelve patients (29%) suffered reconstruction complications, which led to a flap or implant failure in 5 patients. The median time to complication after reconstruction was 8 months. Thirty-two percent of patients with immediate and 20% with delayed reconstruction suffered a complication, respectively. There were no local failures. Smoking (P = .02), use of bolus (P = .03), and the percentage of the chest wall/reconstructed breast target volume that received ≥107% of the prescribed radiation dose (V107) > 11% (P = .03) were associated with increased complication rates. The complication rates were 42% when V107 > 11% versus 12% when V107 < 11%; 58% in smokers versus 17% in nonsmokers; and 42% with versus 7% without bolus. CONCLUSIONS: Plan heterogeneity appears to be associated with the risk of reconstruction complications. Pending further validation, V107 < 11% may serve as a reasonable guide to limit this risk. Further consideration should be given to the selective use of bolus in this setting and optimization of clinical factors, such as smoking cessation.