Stage IIB Research Articles

Tumor tissue modified viral (TTMV)-HPV DNA as a biomarker of treatment efficacy for definitive chemoradiation in anal squamous cell carcinoma: A step towards truly personalized therapy.

10 Background: Cell-free circulating tumor tissue modified viral DNA (ctDNA) has been used as a biomarker to detect recurrence for anal squamous cell carcinoma (ASCC). However, its value in informing treatment modification during definitive chemoradiation (CRT) has yet to be explored. We evaluated ctDNA response during and at completion of definitive CRT to establish patterns of disease response and inform future studies to personalize treatment. Methods: From 11/2022 to 6/2024, 13 consecutive patients with biopsy proven, non-metastatic ASCC received definitive CRT and had ctDNA testing using a commercially available droplet digital quantitative PCR assay. ctDNA testing was done at baseline (pre-CRT), week 4 of CRT, and/or end of CRT, 1-3 months post-CRT, and every 6 months thereafter. CRT included concurrent 5FU/MMC (or capecitabine/MMC) and radiotherapy according to RTOG 0529. Treatment response assessment included: physical exam, anoscopy, and imaging with PET/CT, CT C/A/P +/- MRI abdomen and pelvis. Results: 13 patients had ctDNA testing and 11 patients had HPV-positive ASCC and tested positive for ctDNA. The 11 patients with detectable baseline ctDNA were included in this analysis. The median age at diagnosis was 63 years old. Staging included: 1- Stage IIA, 7- Stage IIB, 1- Stage IIIA, 2- Stage IIIC. 1 patient was cN0, while 11 were cN1. With a median follow-up from completion of CRT of 13 months, 4 patients have persistent or recurrent disease: 2 with distant metastases, 1 with persistent local disease (1 month post-CRT), and 1 with local and distant recurrence. Baseline value of ctDNA did not correlate to stage at diagnosis, rate of clearance during CRT, or likelihood of recurrence. 5 of 11 patients cleared ctDNA by week 4 of CRT. Of 5 patients who cleared ctDNA by week 4 of CRT, 4 remain NED and 1 developed distant metastases. Of 6 patients with persistent ctDNA at week 4 of CRT, 3 have persistent or recurrent disease- 1 local persistence 1 month post-CRT, 1 local and distant recurrence 6 months post-CRT, and 1 with distant recurrence 12 months post- CRT. Among 6 patients who cleared ctDNA by the final week of CRT, 1 patient developed recurrent disease. Among the 4 patients in the series with residual/recurrent disease, 3 of them had not cleared ctDNA by the end of CRT. Of 10 patients with ctDNA testing at 1 month post-CRT, 8 had no detectable ctDNA. 2 patients with persistent (1) or recurrent (1) ctDNA at 1 month post-CRT developed disease recurrence- 1 with distant recurrence and 1 with local and distant recurrence. Conclusions: ctDNA assessment during CRT may provide insight into disease response that can predict patterns of failure and facilitate personalized therapy- treatment intensification, deintensification, or additional testing to detect early metastatic disease. Larger studies and clinical validation are needed.

Adjuvant Pembrolizumab in Stage II Melanoma: Outcomes by Primary Tumor Location in the Randomized, Double-Blind, Phase III KEYNOTE-716 Trial.

Previous results from the KEYNOTE-716 trial demonstrated significantly improved recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) with adjuvant pembrolizumab versus placebo in patients with resected stage IIB or IIC melanoma. We present a posthoc analysis of efficacy according to primary tumor location. KEYNOTE-716 (NCT03553836) is a randomized, multicenter, double-blind, phase III study. Patients aged ≥ 12 years with newly diagnosed, resected stage IIB or IIC melanoma (sentinel node-negative) were randomly assigned (1:1) to pembrolizumab 200 mg every 3 weeks (2 mg/kg up to 200 mg for pediatric patients) or placebo. This post hoc analysis evaluated RFS and DMFS by primary tumor location of the head/neck, trunk, or extremities. Overall, 976 patients were assigned to pembrolizumab (n=487) or placebo (n=489). Median follow-up was 39.4 months (range 26.0-51.4). The hazard ratios {HRs (95% confidence interval [CI])} for RFS were 0.60 (0.38-0.93) for the head/neck subgroup, 0.57 (0.38-0.84) for the trunk subgroup, and 0.69 (0.47-1.02) for the extremities subgroup. The HRs (95% CI) for DMFS were 0.65 (0.37-1.14) for the head/neck subgroup, 0.59 (0.38-0.92) for the trunk subgroup, and 0.53 (0.31-0.90) for the extremities subgroup. RFS and DMFS consistently favored adjuvant pembrolizumab over placebo in most subgroups analyzed in this posthoc analysis from the KEYNOTE-716 trial. These results support the benefit of adjuvant pembrolizumab on RFS and DMFS in patients with resected high-risk stage II melanoma, irrespective of primary tumor location.

Updated results of ALTER-H006: A phase II study of benmelstobart (PD-L1 inhibitor) plus anlotinib as adjuvant therapy in hepatocellular carcinoma (HCC) with high risk of recurrence after radical resection.

601 Background: Although radical resection offers one of the most favorable prognosis for hepatocellular carcinoma (HCC), the rate of postoperative recurrence remains high, which is the primary cause of mortality in HCC patients. The optimal adjuvant treatment strategy for patients is still under active investigation. Herein we evaluated the efficacy and safety of the anti-angiogenic tyrosine kinase inhibitor, anlotinib, plus benmelstobart, a novel programmed death-ligand 1 (PD-L1) inhibitor as an adjuvant treatment for HCC with high risk of recurrence after radical resection. Methods: This study enrolled patients diagnosed with HCC confirmed through histological or cytological examination, whose age was 18-75, with ECOG 0-1, Child-Pugh class A, 4~8 weeks after R0 resection with any of the following high-risk factors for recurrence: a) tumor nodules ≥4; b) portal vein tumor thrombus (PVTT): vp1 or vp2; c) hepatic vein tumor thrombus (HVTT): vv1 or vv2. Enrolled patients received anlotinib (12 mg, p.o., qd, d1-14, q3w) plus benmelstobart (1200 mg, i.v., d1, q3w) until disease recurrence or unacceptable toxicity or up to 18 cycles (~1 year), whichever occurred first. Tumor assessment was performed at the end of the second cycle and every four cycles thereafter, according to RECIST v1.1. The predefined sample size was 37. The primary endpoint was 1-year recurrence-free survival (RFS) rate. Secondary endpoints included RFS, 1-year overall survival (OS) rate, and safety. Results: As the cutoff date of September 13,2024, a total of 38 patients (pts) were enrolled and 35 pts included in per-protocol set analysis. The majority of the 38 pts were male (94.7%, n = 36), and the median age was 56.5 years (range: 33-75). 18 pts (47.3%) had CNLC Stage IIb and 20 (52.6%) had CNLC Stage IIIa HCC. Among them, 35 pts received at least once tumor assessment. According to RECIST 1.1, of the 35 pts, 18 had no recurrence, 15 experienced relapse, 1 dropped out and 1 discontinued due to serious adverse events. The 1-year RFS rate was 59.97% (95%CI: 39.12-79.68) and the primary median RFS was 16.89m(95%CI: 6.82-26.96). The 1-year OS rate was 91.47% (95%CI: 69.23-97.86). 34 of 38 pts (89.5%) experienced treatment-related adverse events (TRAEs). The most common grade 3 TRAEs occurred in 17 pts (44.7%) including hypertension (32%) and neutropenia(5.3%). No grade 4 or 5 TRAEs were observed. Conclusions: The present study indicated that anlotinib plus benmelstobart as adjuvant treatment for HCC with high risk of recurrence after radical resection exhibited promising efficacy and tolerable safety profile. The conclusion should be validated in more participants included subsequently. Clinical trial information: NCT05111366 .

NRG-GI008: Colon adjuvant chemotherapy based on evaluation of residual disease (CIRCULATE-North America).

TPS310 Background: Currently, there are no biomarkers validated prospectively in randomized studies for resected colon cancer (CC) to determine need for adjuvant chemotherapy (AC). However, circulating tumor DNA (ctDNA) represents a highly specific and sensitive approach (especially with serial monitoring) for identifying minimal/molecular residual disease (MRD) post-surgery in CC patients (pts), and may outperform traditional clinical and pathological features in prognosticating risk for recurrence. CC pts who do not have detectable ctDNA (ctDNA-) are at a much lower risk of recurrence and may be spared the toxicities associated with AC. Furthermore, for CC pts with detectable ctDNA (ctDNA+) who are at a very high risk of recurrence, the optimal AC regimen has not been established. We hypothesize that for pts whose CC has been resected, ctDNA status may be used to risk-stratify for making decisions about AC. Methods: In this prospective phase II/III trial, up to 1,912 pts with resected stage IIB, IIC, and III CC will be enrolled. Based on the post-operative ctDNA status using personalized and tumor-informed assay (Signatera, bespoke assay), those who are ctDNA- (Cohort A) will be randomized to immediate AC with fluoropyrimidine (FP)+oxaliplatin (Ox) for 3-6 mos per established guidelines v serial ctDNA monitoring. Patients who are ctDNA+ post-operatively, or with serial monitoring (Cohort B), will be randomized to FP+Ox v more intensive AC with addition of irinotecan (I) for 6 mos. One cycle of chemotherapy is allowed while awaiting ctDNA testing results for cohort assignment. The primary endpoints for Cohort A are time to ctDNA+ status (phase II) and disease-free survival (DFS) (phase III) in the immediate v delayed AC arms. The primary endpoint for Cohort B is DFS in the FP+Ox v FP+Ox+I arms for both phase II and phase III portions of the trial. Secondary endpoints include prevalence of detectable ctDNA post-operatively, time-to-event outcomes (overall survival and time to recurrence) by ctDNA status, and the assessment of compliance to adjuvant therapy. Biospecimens including archival tumor tissue, as well as post-operative plus serial matched/normal blood samples, will be collected for exploratory correlative research. Active enrollment across the NCTN started in June 2022 with CCTG sites joining in August 2023. Current accrual (as of 9-20-2024): 500/1,912. Clinical trial information: NCT05174169 .

Cutaneous Metastasis of Endometrial Adenocarcinoma: An Unusual and Dramatic Presentation of two Cases

Skin metastases from endometrial adenocarcinoma, particularly cutaneous lymphangitis carcinomatosis, are rare. We present two cases of endometrial adenocarcinoma that recurred as lymphangitic carcinomatosis after presumed complete resection. Case 1 is a 71-year-old woman with a history of breast adenocarcinoma, who developed painful erythematous lesions and a verrucous plaque in the pubic area three months after surgery for endometrial adenocarcinoma. A skin biopsy confirmed carcinomatous lymphangitis, and she died four months later. Case 2 is a 56-year-old woman with stage IIB endometrioid adenocarcinoma, who developed erythematous plaques and lymphedema on the left thigh a year after treatment. A biopsy confirmed cutaneous lymphangitis carcinomatosis, and she died five months later. Cutaneous lymphangitis carcinomatosis is an uncommon form of skin metastasis, typically seen in breast cancer but rarely in endometrial adenocarcinoma. Early recognition is essential, as it can mimic benign dermatologic conditions. The prognosis is poor, with treatment often being palliative and ineffective. These cases highlight the importance of considering skin metastasis in patients with a history of gynecological cancer presenting with new cutaneous lesions

Thermal ocular burns and evaluation of associated limbal stem cell deficiency in the light of global consensus.

The aim of the present study is to examine the demographic data and clinical features of ocular surface injuries due to thermal burns and to evaluate LSCD in the light of global consensus. Thirty-three eyes of 20 cases with ocular surface injury due to thermal burn who attended to the clinic between 2012 and 2023 were included in the study. LSCD severity was staged according to the global consensus which was published in 2019. The mean age of 20 cases was 45.8 ± 13.362 (19-78) and female/male ratio was 4/16. The causes of thermal burns were exposure to fire in 10 (50%), molten metal in 5 (25%), pressure cooker explosion in 3 (15%), and hot water in 2 (10%) cases. The number of cases who recovered without sequelae was 15. The observed sequelaes were LSCD (21.2%), symblepharon (6.06%), and corneal opacity (9.09%). Considering the distribution of LSCD, 28.57% of the eyes were Stage Ia, 14.28% were Stage Ib, 28.57% were Stage IIb, 28.57% were Stage III. The symblepharon was Stage IIa in 2 patients. Surgery was performed in 4 patients with sequelae (penetrating keratoplasty in 1, corneal debridement in 1, limbal autograft in 1, amniotic membrane transplantation + symblepharon excision + limbal autograft in 1 eyes). Most of the thermal injuries heal without sequelae. If a sequela takes place, the most common one is severe LSCD-half of which are severe.

A Study on the Response of Concurrent Chemoradiation with Gemcitabine Versus Cisplatin in Patients with Locally Advanced Cervical Carcinoma

Introduction Cervical cancer is the most common cause of cancer death in women. Currently, platinum-based concurrent chemoradiation therapy is the standard of care for locally advanced cervical cancer but treatment results are disappointing, particularly for women with bulky tumors. Several non-platinum-based agents with concurrent chemoradiation have been evolved to improve this result. Objective To compare the response between concurrent chemoradiation with gemcitabine and cisplatin followed by intracavitary radiotherapy in patients with locally advanced cervical carcinoma. Material and methods This was a quasi-experimental study, where 66 patients with untreated invasive squamous cell carcinoma of the cervix of stage IIB to stage IVA were enrolled from the Radiation Oncology Department of Rajshahi Medical College Hospital from April 2019 to March 2020. The duration of the study was 2 years. In each arm 33 patients were assigned to receive 150 mg/m² of gemcitabine (arm A) or received 40mg/m2 of cisplatin (arm B) weekly along with external beam radiation therapy (EBRT). EBRT dose was 50 Gy in 25 daily fractions followed by intracavitary radiotherapy (ICRT) of 21 Gy in 3 fractions. Results The mean age was 45.4 years & 47.3 years in arm A & B respectively. Most patients were in the stage IIB group (59.1% patients) and most were moderately differentiated (62.1% patients) in both arms. After 3 months of treatment, the complete response was found in 81.8% &72.7% of patients and partial response was seen in 12.1% & 18.2% of patients in arm A & B respectively (p=0.678). The grade 2 and 3 hematological toxicities (anemia, neutropenia, thrombocytopenia) were more common in arm A compared to arm B (p<0.05). The grade 2 and 3 proctitis & skin toxicity were higher in arm A & renal toxicity was higher in arm B (p=0.163). Conclusion Concurrent chemoradiation with gemcitabine can be used as an alternative to cisplatin when cisplatin is contraindicated. However, further large, randomized study is needed to reach any form of conclusion.

Re-evaluating prognostic factors for cervical cancer with lymph node metastasis: a Japanese multicenter cohort study based on FIGO 2018.

In 2018, the International Federation of Gynecology and Obstetrics (FIGO) revised its cervical cancer staging system to enhance clinical relevance, notably by categorizing lymph node metastases (LNM) as an independent stage IIIC. This multicenter study evaluates the prognostic implications of the FIGO 2018 classification within a Japanese cohort. This study included 1468 patients with cervical cancer. Initial FIGO 2009 stages were restaged under FIGO 2018. Stage IIIC was further compared based on the location of LNM (pelvic or para-aortic, i.e., IIIC1 and IIIC2, respectively), local tumor stage, and histology. A total of 345 cases (27.4%) were upstaged to stage IIIC, which exhibited a poorer prognosis compared to stage II (HR, 2.12; 95% CI 1.29 - 3.48; p = 0.004) and better than stage IIIAB (HR, 0.46; 95% CI 0.27 - 0.78; p = 0.004). Notably, stage IIIC2 showed a significantly worse prognosis than IIIC1 (HR, 2.32; 95% CI 1.37 - 3.93; p = 0.003). Subdivisions of stage IIIC1 (T1, T2, and T3AB) displayed significantly varied prognoses, with the prognosis for IIIC1-T3AB similar to that of stage IIIAB. In contrast, all subdivisions of IIIC2 showed uniformly poor outcomes. Multivariate analysis of stage IIIC patients revealed that para-aortic LNM, adenocarcinoma and adenosquamous carcinoma histology, and local T3AB tumor remained significant. The classification of para-aortic LNM as stage IIIC2 has proven to be of critical relevance in the Japanese cohort. However, the prognostic impact of stage IIIC1 remains influenced by local tumor factors and histological subtypes.

Early diagnosis of lung cancer using a sensor gas analysis complex: case report

Background. Currently, low-dose computed tomography (LDCT) is the only screening test that reduces the risk of death from lung cancer. However, there are a number of disadvantages, such as lack of widespread use, high cost, high false-positive rate and the need to conduct studies only in high-risk groups, which significantly limit mass screening. exhaled breath analysis, which uses sensitive breath sensors, is a promising method to improve early diagnosis of lung cancer. Cancer Research Institute of Tomsk National Research Medical Center together with Tomsk State University and Tomsk Polytechnic Research Institute has developed a gas analysis complex capable of analyzing the gas composition of exhaled air with remote sampling from bags. during the study, data obtained by digitizing signals from gas analysis system sensors and patient metadata are recorded in a database for subsequent automated processing and analysis using a neural network. Case description. A 48-year-old female patient with a long history of smoking came to the clinic of the Cancer Research Institute for consultation with suspected pathological infiltration around the celiac trunk detected by abdominal CT. As a clinical trial of the developed gas analytical complex for cancer detection, a sample of exhaled air was taken, and the comparison of the composition of volatile organic compounds (VOCs) with that in the control group (healthy individuals) revealed abnormalities characteristic of lung cancer. the patient underwent a chest CT scan, which revealed stage IIB peripheral cancer of the lower lobe of the left lung. the original sensor gas analysis complex, which has no analogues in Russia, was used for the first time in the detection of lung cancer. the data obtained allowed us to suspect the presence of lung tumor in the patient and perform radical surgical treatment. the composition of VOCs in exhaled air was assessed on day 10 after surgery, and no significant changes in the composition of exhaled air were observed. Conclusion. Machine learning algorithms are actively used to diagnose socially significant diseases. the platforms being developed based on arrays of chemical sensors with data analysis using a neural network are promising candidates for implementation in screening activities.

Comparative genomic analysis unveiling the mutational landscape associated with premalignant lesions and early-stage gastric cardia cancer.

This study enrolled 10 patients diagnosed with premalignant lesions and early-stage gastric cardia adenocarcinoma (GCA), confirmed through endoscopic examination. These patients were subjected to next-generation sequencing (NGS) using a customized 1123-gene panel to identify genetic alterations and signaling pathways. The results were compared to stage IIB to IV GCA samples from the cancer genome atlas (TCGA) and a cohort of Hong Kong patients. The study provides insights into the molecular drivers of GCA progression, with potential therapeutic implications. A total of 10 patients diagnosed with premalignant and early-stage GCA were subjected to NGS targeted 1123-panal testing. Genetic alterations characteristics and signaling pathways were defined and analyzed. These findings were compared with the mutation features of stage IIB to IV GCA samples from the TCGA and another GCA cohort of HongKong patients (HK cohort). Additionally, therapeutic implications were also evaluated. In premalignant lesions and early-stage GCA, driver genes, such as TP53, ARIDA and LRP1B were found to have high mutation rates and showed no significantly different in driver gene mutation and tumor mutational burden with stage IIB to IV GCA in both the HK and TCGA-GCA cohorts. However, EPHA2 showed a significantly higher mutation rate in premalignant and early-stage GCA compared to IIB to IV GCA. The majority of 10 cancer-related signaling pathways were found to be activated in premalignant and early-stage GCA. Furthermore, 80% patients had corresponding potential therapeutic inhibitors based on molecular mutation results in our cohort. Certain mutational characteristics involved in the occurrence and progression of GCA are already present in premalignant lesions and early-stage GCA, which can be assessed and prevented through early molecular testing. Additionally, EPHA2 mutations are more common in premalignant lesions and early-stage GCA, which provided potential biomarkers for the diagnosis and detection of premalignant lesions and early-stage GCA.

Adjuvant Immunotherapy After Resected Melanoma: Survival Outcomes, Prognostic Factors and Patterns of Relapse.

Anti-PD-1-based immunotherapy has improved outcomes in stage IIB to IV resected melanoma patients in clinical trials. However, little is known about real-world outcomes, prognostic factors and patterns of relapse. This is a retrospective multicenter observational study including patients with resected melanoma treated with subsequent anti-PD-1-based adjuvant immunotherapy. Data on clinical and demographic characteristics, delivered treatment, prognostic factors, time and pattern of relapse were collected. We included 245 patients from eight centers; 4% of patients were at stage IIB-C, 80% at stage IIIA-D and 16% at stage IV. Recurrence-free survival (RFS) rates at 18 and 36 months were 60% and 48%, respectively, with a median RFS of 33.7 months. Prognostic factors associated with recurrence were melanoma primary site (HR 2.64, 95% CI 1.15-6.01) and starting adjuvant therapy more than 12 weeks after the last resection (HR 1.68, 95% CI 1.13-2.5); presence of serious immune-related adverse events was associated with better RFS (HR 0.4, 95% CI 0.19-0.87). Early relapses accounted for 63% of the total recurrences, with a higher number of metastatic sites (18%); in contrast, late relapses presented more frequently with brain metastases (20%). In our patients with resected melanoma who underwent anti-PD-1-based adjuvant immunotherapy, survival outcomes were worse than those reported in clinical trials. Primary melanoma site and time interval between the last resection and the start of adjuvant therapy were associated with survival.

Comparative evaluation of TNM staging systems (eighth vs. ninth edition) for the non-surgical treatment of localized and locally advanced anal squamous cell carcinoma: Prognostic significance of T classification and lymph node status.

This study aims to compare the survival discrimination of the Tumor-Node-Metastasis (TNM) eighth and ninth editions for patients with localized and locally advanced (LLA) anal squamous cell carcinoma (ASCC) treated non-surgically and to evaluate the prognostic impact of T classification and lymph node (LN) status with data from the Surveillance, Epidemiology, and End Results database. We retrospectively included 6,876 patients in the comparison. We observed the inversion of survival outcomes for stages IIB and IIIA diseases in the TNM eighth edition [median overall survival (OS): 112 months for stage IIB vs. not reached for stage IIIA]. By contrast, it demonstrated improvement in the TNM ninth edition (median OS: not reached for IIB disease vs. 120 months for IIIA disease, P<0.001). In the correlation analysis, we observed an increased correlation between T classification and TNM staging systems (r value increased from 0.78 to 0.93) and a decreased correlation for the LN status (r value decreased from 0.83 to 0.59). For OS, variable importance analysis demonstrated more weight of importance for the T classification than the LN status (0.0871 vs. 0.0048). Additionally, decision curve analysis and time-dependent receiver operating characteristic analysis confirmed the prognostic accuracy of T classification rather than the LN status. In conclusion, TNM ninth edition is a better prognostic indicator than the eighth edition for patients with LLA ASCC treated non-surgically. T classification plays a more important prognostic role than the LN status and warrants further validation.

Paraneoplastic limbic encephalitis in a patient with small cell lung cancer. Case report

Paraneoplastic limbic encephalitis (PLE) is a rare autoimmune neurological syndrome caused by selective involvement of the limbic system with the development of neuropsychiatric symptoms and cognitive impairment. PLE is associated with malignancies. We observed PLE in a patient with small cell lung cancer (SCLC). Patient B. complained of severe weakness, headache attacks, irritability, memory loss, and cramps in the muscles of the limbs for 2 months. Contrast-enhanced magnetic resonance imaging of the brain showed signs of PLE. Anti-neuronal antibodies were detected in the blood serum: anti-Hu, anti-CV2 and anti-Ma2, anti-amphiphysin. In the cerebrospinal fluid, anti-Hu antibodies, lymphocytosis of 88%, and increased protein of 0.6 g/L were found. The patient was consulted by a neurologist and diagnosed with PLE. No treatment was administered. After 2 months, the patient reported a significant deterioration. Memory impairment progressed, convulsive seizures with short-term loss of consciousness became more frequent, and the patient became aggressive and withdrawn. Positron emission tomography combined with computed tomography with 18F-fluorodeoxyglucose was performed. There was an excessive radiopharmaceutical uptake in a limited area of the medial parts of the left temporal lobe. A tumor was detected in the upper lobe of the right lung. A bronchoscopy with biopsy was performed. Histological examination showed SCLC. Clinical diagnosis: SCLC of the right lung, stage IIb cT2bN1M0; PLE. Cytotoxic and immunotherapy were administered. The case shows that PLE is a rare neurological syndrome associated in most cases with SCLC, usually in the early stages of the malignancy. Neuropsychiatric and cognitive disorders and seizures are predominant in clinical presentation. PLE neuroimaging is performed using contrast-enhanced magnetic resonance imaging and positron emission tomography combined with computed tomography with 18F-fluorodeoxyglucose, the latter being the method of choice. The presence of antineuronal antibodies in serum and cerebrospinal fluid confirms the autoimmune (paraneoplastic) nature of the process.

Role of preoperative transarterial chemoembolization (TACE) in intermediate-stage hepatocellular carcinoma (Hong Kong liver cancer stage IIB).

Transarterial chemoembolization (TACE) has an established role in advanced HCC. The present study evaluates the role of TACE as a neoadjuvant modality in the management of intermediate HCC [Hong Kong Liver Cancer (HKLC) stage IIB]. A retrospective analysis of HCC patients treated between January 2010 and August 2022 was performed. Patients belonging to intermediate-stage HCC (HKLC IIB) were divided into two groups, upfront surgery (UPS) and post-TACE (pTACE). Propensity score matching was done, and the primary endpoint of the study was overall survival (OS). A total of 247 patients of HKLC IIB were identified during this period. Of these, 77 patients in each group were considered for analysis after propensity matching. The median follow-up was 36.4months (0.46-144.26). In the propensity matched population (n=154), on an intention-to-treat analysis, the median OS of the UPS group and the pTACE group was 30.06 and 39.26months, respectively (p value=0.77). In patients who underwent curative resection, the median OS of the UPS group was 30.68 versus 90.97months in the pTACE group (p value=0.006) and median DFS was 13.56months for the UPS group versus 44.02months in the pTACE group, respectively (p value=0.013). In intermediate-stage hepatocellular carcinoma (HKLC IIB), pTACE can be used to better select patients with borderline resectability. Survival was significantly improved in patients who received pTACE and were able to undergo surgical resection.

Comparison between The Efficacy of Concurrent Chemo-Radiation with Gemcitabine Followed by Intracavitary Radiotherapy in Patients with Locally Advanced Cervical Carcinoma

Introduction: Commonest threatening cancer in our Asian round is Cervical cancer. Currently, platinum-based concurrent chemo-radiation therapy is the standard of care for locally advanced cervical cancer but treatment results are disappointing, particularly for women with bulky tumors. To improve this result, several non-platinum-based agents with concurrent chemo-radiation have been evolved. Material and Methods: This was a quasi-experimental study, where 33 patients with untreated invasive squamous cell carcinoma of the cervix of stage IIB to stage IVA were enrolled in the study from the Radiation Oncology Department of Rajshahi Medical College Hospital from April 2019 to March 2020. Duration of the study was 2 years. All patients received 150 mg/m² of Gemcitabine weekly along with external beam radiation therapy (EBRT). EBRT dose was 50 Gy in 25 daily fractions followed by intracavitary radiotherapy (ICRT) of 21 Gy in 3 fractions. Results: The mean patient age was 45.4 years. Most patients were in stage IIB (59.1%) with moderately differentiated tumors (62.1%). After three months of treatment, 81.8% showed complete response, 12.1% partial response, and 6.1% disease progression. Grade 2 and 3 hematological toxicities were common, including anemia (60.6% grade 2; 24.2% grade 3) and neutropenia (24.2% grade 2; 6.1% grade 3). Other side effects included diarrhea (42.4%), proctitis (36.4%), skin toxicity (45.5%), mild renal toxicity (3%), and grade 2 cystitis (9.1%). Conclusion: Gemcitabine-based concurrent chemo-radiation is a potential alternative for patients contraindicated for Cisplatin. However, larger randomized studies are needed to confirm its safety and efficacy.

Is core decompression and bone marrow concentrate with demineralized bone matrix and platelet-rich fibrin suitable for treating femoral head osteonecrosis?

The aim of this article is to determine the safety and efficacy of core decompression (CD) combined with injection of autologous bone marrow concentrate (BMC), demineralized bone matrix (DBM), and platelet-rich fibrin (PRF) for treating femoral head osteonecrosis. Seventy-seven patients (53 males and 24 females) for a total of 87 hips were treated for hip osteonecrosis with CD combined with injection of autologous BMC, DBM, and PRF at Rizzoli Orthopedic Institute from September 2008 to December 2019. Patients were assessed at baseline, at 45 days, and at 3, 6, 12, 24, and 36 months postoperatively. The primary outcome was the survival rate of hips not converted to total hip arthroplasty (THA). The secondary outcomes were (I) radiographic positive evolution assessed by X-ray films and magnetic resonance imaging and (II) the clinical symptoms evaluated with the Harris Hip Score (HHS). Eighty-seven hips from 77 patients with femoral head osteonecrosis (FHON), 60 males and 27 females, with a median age of 34 years (range 15-55) were included. The cause of necrosis was steroid treatment in 30 patients (17 of these for hematological malignancies, 2 for lupus, 1 for Churg-Strauss syndrome, and the remaining for other causes), 1 was alcohol-related, 4 followed hip injury, while 15 patients had idiopathic causes. THA was carried out in 20 hips (40%). These patients had lesions classified as IIa on the Ficat stage in four cases, six were IIb, nine were III, and one was 4. No CD-related complications were found during THA surgery or at the last follow-up in these cohorts of patients. Radiographic progression of the FHON was found in 14 hips (28%), with a higher percentage on Ficat's stage IIb. There were procedure-related complications in two hips, including one femoral neck fracture and one deep infection. Nineteen hips with successful treatment had good to excellent functional results at a 3-year follow-up or more (HHS ≥ 80). The long-term outcomes of treatment with CD and injection with BMC combined with DBM and PRF are promising to prevent femoral head collapse in patients with FHON. Moreover, CD does not influence the outcome in cases of THA.

The Added Role of Diffusion-Weighted Magnetic Resonance Imaging in Staging Uterine Cervical Cancer.

Cervical cancer is considered one of the most common gynecological malignancies with an increased incidence in developing countries. Magnetic resonance imaging (MRI) plays a valuable role in staging cervical cancer and providing valuable information necessary for selecting the appropriate treatment plan, while closely correlating with the prognosis of the patient. The aim of this study is to assess the diagnostic value of diffusion-weighted imaging (DWI) in the preoperative loco-regional staging of cervical carcinoma. Our purpose is to establish apparent diffusion coefficient (ADC) values of cervical carcinoma compared with normal cervical tissue and their variability based on different pathological characteristics of the lesions. It is a retrospective analysis of 57 patients diagnosed with cervical cancer, who underwent MRI examinations. The study evaluated the aspect of the lesions on T2-weighted imaging, DWI, ADC maps, and pre- and post-contrast T1-weighted imaging with fat saturation. The ADC mean values ranged between 0.63 × 10-3 mm2/second and 0.99 × 10-3 mm2/second (mean 0.79) for tumoral tissue and 1.33 × 10-3 mm2/second and 1.74 × 10-3 mm2/second (mean 1.59) for surrounding non-affected cervical tissue. The ADC mapping showed a decreasing trend with the increased sizes of the tumors (p<0.001). The ADC mean showed lower values with increased International Federation of Gynecology and Obstetrics (FIGO) stage of the tumors. The ADC mean value for cases that had spread to other organs (IVA+IVB) was significantly lower than that of the early stages (IB1 + IB2 + IIA2), stage IIB, and stages IIIA+IIIC1+IIIC2 (p<0.001). The ADC mean value of stage III disease was significantly lower than that of stage IIB, respectively early stages (p<0.001). The ADC mean value of the stage IIB tumor was significantly lower than that of the early stages (p<0.001). The differences in ADC mean values based on the histopathological type and differentiation grade were not statistically significant. The ADC mean value of the cases with positive pelvic lymph nodes was significantly lower than in those with negative lymph nodes (p<0.001). ADC mean values of cervical carcinoma are significantly lower than those from unaffected uterine tissue and they also correlate with the severity of the disease. The advancements and additional capabilities DWI can bring are the elements of interest in this article. Using DWI means a more accurate capability in diagnosing cervical cancer, providing a compelling argument for its integration into standard clinical practice. This study discusses the quantitative imaging parameters of DWI such as ADC values, which can provide objective measurements for tumor evaluation. These parameters can be standardized and used across different institutions, enhancing the reproducibility and reliability of imaging findings.

Catheter-Directed Arterial Thrombolysis with a Low-Dose Recombinant Tissue Plasminogen Activator Regimen for Acute Lower Limb Ischemia-Results of the First Regional Registry of Acute Limb Ischemia in Romania.

Acute limb ischemia is a limb-threatening condition that is associated with a high degree of mortality and morbidity, with the latter related to acute kidney injury and rhabdomyolysis that can rapidly lead to multiple organ failure. The aim of this study was to assess the efficacy and safety of catheter-directed arterial thrombolysis in acute lower limb ischemia in the Department of Vascular Surgery, Timișoara, Romania. A total of 158 patients (114 males-72.15% and 44 females-27.85%) with symptoms of acute lower limb ischemia were admitted and treated with catheter-directed arterial thrombolysis following our protocol. The amputation-free survival rate at 1 month after the thrombolysis was 82.3%, and at 6 months it was 77.85%. The performance of additional procedures to obtain distal perfusion was predictive of an improved outcome at 30 days. The estimated survival rate at 6 months was 84.81% (SE 0.02). The mean survival time was 158.74 days. We recommend the usage of a thrombolytic regimen in patients with a life expectancy of more than 6 months, even in Rutherford stage IIb patients, if there is no major impairment in the sensorial and mobility function of the ischemic leg.

In a prospective, multicenter study, the 31-GEP identified patients at increased risk of tumor recurrence and added significant prognostic value to AJCC staging

Cutaneous melanoma (CM) guidelines base management decisions on a patient’s American Joint Committee on Cancer (AJCC) tumor stage. However, limitations in staging accuracy suggest additional tools could improve risk-aligned patient management decisions. The 31-gene expression profile (GEP) test identifies patients with CM with low (Class 1A), intermediate (Class 1B/2A), or high (Class 2B) risk for sentinel lymph node (SLN) positivity, recurrence, metastasis, and death. In this multicenter, prospective study, we validated the 31-GEP for risk of recurrence and demonstrated the added value of 31-GEP to AJCC staging. Patients were included in the prospective CONNECTION study if they were tested with the 31-GEP from 2018 to the present (n=876). Survival was estimated using Kaplan-Meier analysis and 31-GEP stratification tested with the log-rank test. Cox regression was performed to identify predictors of recurrence. ANOVA was used to compare Cox models for the most accurate recurrence prediction. Patients with a Class 1A result had significantly higher 3-year recurrence-free survival than those with a Class 1B/2A or Class 2B result (98.5% vs. 80.8% vs. 63.0%, p&lt;0.001). The 31-GEP had higher sensitivity (75.0% vs. 37.5%) and negative predictive value (98.6% vs. 96.9%) than AJCC staging. Multivariable analysis demonstrated that Class 1B/2A (hazard ratio, HR=3.12, p=0.037) and Class 2B (HR=5.91, p=0.002) were significant predictors of recurrence in addition to stage IB (HR=4.02, p=0.02), IIA (HR=6.06, p=0.006), IIC (HR=17.14, p&lt;0.001), and III (HR=8.84, p&lt;0.001). Stage IIB (HR=4.63, p=0.057) was not significant. Comparing a staging-only model to a 31-GEP+staging model showed that adding 31-GEP to staging significantly improved prediction accuracy over staging alone (ANOVA: c2=10.58, p=0.005). In this prospective study, the 31-GEP stratified risk of recurrence, was a significant predictor of recurrence, and added significant predictive value to AJCC staging. The 31-GEP identifies patients at high risk of recurrence who should be managed more intensely, and adding 31-GEP to staging allows better risk-aligned care decisions, which can lead to improved patient outcomes.

The correlation of Alkaline Phosphatase, lactate dehydrogenase, C-Reactive protein, erythrocyte sedimentation rate, and apparent diffusion coefficient values with Enneking staging and osteosarcoma subtypes

Apparent diffusion coefficient (ADC) values obtained from Magnetic Resonance Imaging (MRI) have shown potential as predictors of osteosarcoma staging and subtype, along with laboratory results for alkaline phosphatase (ALP), lactate dehydrogenase (LDH), c-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). However, studies investigating this correlation are still relatively limited. These tests may be an alternative for osteosarcoma staging and subtyping, especially in low-resource settings. This study aims to investigate the correlation between the ADC value and laboratory findings with the staging and subtype of osteosarcoma. This retrospective study analyzed data from osteosarcoma patients from August 2021 to August 2023, including serum levels of ALP, LDH, CRP, ESR, and ADC values from MRI. A study of 39 osteosarcoma patients found that most were male (61.5%), with an average age of 19. The distal femur was the most common tumor location (33.3%), and osteosarcoma chondroblast type was the predominant subtype (30.8%). Enneking stage IIB was the most prevalent (79.5%). ALP, LDH, CRP, and ESR biomarkers significantly correlated with Enneking staging (p&lt;0.05). However, no correlations were found between these biomarkers and osteosarcoma subtype (p&gt;0.1). Additionally, no significant correlations were observed between the mean ADC and Enneking staging (p=0.061) or osteosarcoma subtype (p=0.084). ALP, LDH, CRP, and ESR levels have a strong and significant correlation to the staging of Enneking osteosarcoma. However, the mean ADC values on MRI do not have a significant correlation to the osteosarcoma subtype based on histopathology.