T4 Disease Research Articles

Neoadjuvant chemotherapy followed by definitive local treatment in locally advanced sinonasal squamous cell carcinoma

BackgroundSinonasal squamous cell carcinoma (SCC) is a rare disease entity, comprising less than 5% of malignancies of the head and neck. While surgery is the primary treatment approach, neoadjuvant and adjuvant therapies play crucial roles in enhancing the prognosis of patients undergoing treatment with the goal of cure. In this study, we aimed to explore the treatment outcomes of neoadjuvant chemotherapy (NAC) in patients with locally advanced sinonasal SCC.MethodsMedical records of patients diagnosed of locally advanced (cT3-4b, N0-3) sinonasal SCC treated with a definitive aim between January 2005 and March 2023 were retrospectively reviewed. Patients were categorized into the following groups based on the initial treatment: NAC followed by surgery, NAC followed by concurrent chemoradiotherapy (CCRT), definitive CCRT, or upfront surgery. Initial treatment plan was decided by a multidisciplinary team. Primary endpoint was overall survival (OS) and objective response rate, and secondary endpoints were progression free survival (PFS), cumulative incidence of local and distant failures, and treatment-related toxicity. The treatment response was assessed according to the RECIST criteria.ResultsTotal 126 patients were included, and the median follow-up period was 25.6 months. The objective response rate to NAC was 48.2%. The subsequent resection rate was 70%, 42.9%, and 16.7% for patients with stage T3, T4a, and T4b disease, respectively. Two-year progression-free survival did not differ significantly between the NAC followed by surgery and upfront surgery groups (53.6% vs. 60.6%, P = 0.615) or between the NAC followed by CCRT and definitive CCRT groups (26.7% vs. 37.4%, P = 0.506).ConclusionNAC may be a valuable treatment option for patients with locally advanced sinonasal SCC, as it provides an opportunity for curative surgery and exhibits non-inferior oncological outcomes compared with upfront definitive local treatments.

Impact of Retroperitoneal Lymphadenopathy (RPLN) on the Outcomes of Locally Advanced Gall Bladder Cancer (GBC) Following Chemotherapy (CT) or Chemotherapy Followed by Consolidation Chemoradiotherapy (CTRT).

Retroperitoneal lymphadenopathy is considered a metastatic disease in GBC; however, some surgical series of radical surgery with enlarged RPLN who underwent RPLN dissection have shown results marginally inferior to those without enlarged RPLN. Radiological RPLN comprises a major proportion of advanced non-metastatic GBC. There is dilemma in the intent of treatment to be offered in such cases. We are reporting our series of outcome of GBC with RPLN treated with first-line CT followed by consolidation CTRT. Non-metastatic locally advanced GBC with good performance status (KPS ≥ 80) were initiated on first-line CT (cisplatin-gemcitabine), and thereafter, responders were evaluated by CECT-angiography and PET-CT scan for resectability. If found unresectable, they were offered consolidation CTRT to a dose of 45Gy by conventional fractionation (3D-CRT technique) along with concurrent capecitabine at 1250mg/m2 to GBC and regional lymphatics including RPLN. Thereafter, boost dose of 9Gy/5# was given to GBC only. Response assessment was done using CECT abdomen by RECIST criteria v 1.1. Outcomes (overall survival) of the two groups (RPLN vs non-RPLN) were computed with Kaplan-Meier survival curves and chi-square tests using SPSS v 20. Among 189 patients of advanced non-metastatic GBC recruited from 2011 to 2022, 80 had RPLN. The demographic features of both groups were comparable. Overall, 68% of the patients were women, 30% underwent upfront stenting for obstructive jaundice, and 90% had T3 and T4 disease. Only 10% had undergone upfront laparoscopic staging and had pathologically proven RPLN. Forty percent of the patients received four cycles of CT only and 50% of the patients received six cycles or more and 33% received CTRT. By RECIST criteria, 10% vs 16% achieved complete response (CR), 39% vs 41% achieved partial response (PR), 16% vs 15% achieved stable disease (SD), 2.7% vs 6% had disease progression (PD), and 14.5% vs 3.7% were non-evaluable in non-RPLN group vs RPLN group, respectively. 12% vs 6% could undergo radical surgery in non-RPLN group vs RPLN group (p = 0.03). The median OS was 9months (95% CI 7.6-10.3months) vs 10months (95% CI 8-9.8months) (p = NS) in non-RPLN group vs RPLN group, respectively. In those who received CT only, the median OS was 7months vs 8months, while in those who received CT followed by CTRT, the median OS was 14months vs 13months (p = 0.65) in non-RPLN group vs RPLN group, respectively. Based on this analysis, we conclude that RPLN constitutes a major proportion of advanced non-metastatic GBC and has outcomes similar to those without RPLN if treated with radical intent. RPLN should not be considered a metastatic disease and should be treated with radical intent.

Phase II Trial of Adjuvant S-1 Following Neoadjuvant Chemotherapy and Surgery in Patients with Locally Advanced Esophageal Squamous Cell Carcinoma: The PIECE Trial.

Neoadjuvant chemotherapy followed by surgery (NAC-S) is the standard therapy for locally advanced esophageal squamous cell carcinoma (ESCC) in Japan. The aim of this phase II trial was to assess the efficacy and safety of the addition of adjuvant S-1 after R0 resection in ESCC patients who received NAC-S. Key eligibility criteria included clinical stage IB-III (without T4 disease) ESCC, age 20-75years, and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Patients received adjuvant therapy with four cycles of S-1 (80mg/m2/day) administered orally for 4 weeks of 6-week cycles. The primary endpoint was 3year relapse-free survival (RFS). If the lower confidence limit for 3year RFS was >50%, we judged that the primary endpoint of this study was met. A total of 52 patients were enrolled between January 2016 and January 2019. Two patients were excluded from analysis; five patients were determined to have R1 or R2 resection, and seven patients did not receive adjuvant S-1. The 3-year RFS and overall survival rates in the intention-to-treat population were 72.3% (90% confidence interval [CI] 59.9-81.5) and 85.0% (90% CI 73.9-91.6), indicating that the primary endpoint was met. Grade ≥3 adverse events with an incidence ≥10% included neutropenia (13.2%), anorexia (13.2%), and diarrhea (10.5%). There were no treatment-related deaths. Adjuvant S-1 after NAC-S showed promising efficacy with a manageable safety profile for patients with resectable ESCC and warrants further evaluation in larger studies.

7478 Effects of RAI on Papillary Thyroid Carcinoma with Positive Lymph Nodes

Abstract Disclosure: K.N. Rachmasari: None. A. Osman: None. D. Toro Tobon: None. S.B. Lund: None. D.J. Merlino: None. A.R. Hsu: None. M.M. Ryder: None. Background: In low-risk papillary thyroid cancer (PTC), radioactive iodine (RAI) remnant ablation has shown no impact on disease recurrence rates, which are overall low. The role of adjuvant RAI in intermediate risk disease (i.e. T3, N1) remains unproven with no randomized clinical trials to objectively assess efficacy. Thus, in our institution, its use is highly heterogenous. We retrospectively investigated the effects of adjuvant RAI on recurrence and recurrence free survival (RFS) in patients with PTC and positive cervical lymph nodes (CLN). Methods: We performed a retrospective review of patients who underwent surgery at Mayo Clinic Rochester, MN for PTC between January 2007 and December 2016. Adult patients with Tx-T3 disease according to the 8th edition of American Joint Committee on Cancer (AJCC) were identified. Patients with positive CLN (N1) and a minimum follow up of 36 months were included. Demographics, clinicopathologic characteristics, use of RAI therapy and recurrence were analyzed. Results: A total of 367 patients with PTC, Tx-3, N1, M0 were identified, of which 187 received adjuvant RAI and 180 did not. Most patients were female (63.8%), with a median age of 44 years (IQR 34-54), and a median follow up of 77 months (IQR 58.5-101.5). There were no differences in age, type of surgery, histology, multifocality, and follow up period between the RAI and no RAI subgroups. Adjuvant Thyrogen-stimulated or thyroid hormone withdrawal-based RAI was recommended at the discretion of the treating provider and/or per patient preference. Diagnostic I-123 whole body scans were performed in all patients and mostly demonstrated remnant uptake. The median dose of I-131 was 75 mCi (range 50-100). Recurrence was defined by new occurrence of disease after at least a year of absence of clinical, biochemical, and imaging evidence of disease since initial surgery. Within the entire cohort, 35 (9.5%) developed recurrence with a median time of 41 months (28-59.5). Overall, recurrence rate and RFS were not significantly different between both subgroups (p = 0.2). A subanalysis was performed in patients with clinically detectable nodal disease (n = 161), defined by abnormal cervical lymph node on preoperative neck ultrasound with or without positive fine needle aspiration biopsy. Overall recurrence rates were 17 (10.6%) in this group. There were no differences in recurrence rates and RFS in those that received RAI versus those that did not (p = 0.8). Conclusions: In patients with intermediate risk PTC defined by nodal disease and/or T3 disease, recurrences were not different between patients that did or did not receive adjuvant I-131 therapy postoperatively. A randomized, noninferiority study of adjuvant I-131 compared to no I-131 postoperatively for N1 disease is needed to determine the benefit of near total thyroidectomy and adjuvant I-131 for this cohort. Presentation: 6/3/2024

Lateral lymph node metastasis without mesenteric lymph node involvement in middle-low rectal cancer: Results of a multicentre lateral node collaborative group study in China

BackgroundCharacteristics and prognoses of lateral lymph node (LLN) metastasis but not mesenteric lymph node (LN) metastasis are poorly understood. This study explored patterns of mesenteric and LLN metastases in rectal cancer patients. MethodThis retrospective, multicentre study was conducted at three institutions and included patients who underwent total mesorectal excision (TME) with lateral lymph node dissection (LLND) for rectal cancer (n = 271). ResultsAmong the patients with LLN metastases, 210 patients (77.5 %) with clinical stage T3-4 disease and 157 patients (57.9 %) with clinical stage N1-N2 disease underwent TME as well as LLND. The prognoses of patients with metastasis confined to LLNs were significantly better than those of patients with both mesenteric and LLN metastases (3-year overall survival: 85.0 % vs. 51.0 %, p = 0.005; 3-year disease-free survival: 75.0 % vs. 26.5 %, p = 0.003) and were similar to those of patients with metastasis confined to mesenteric LNs (3-year overall survival: 85.0 % vs. 83.8 %, p = 0.607; 3-year disease-free survival 75.0 % vs. 68.8 %, p = 0.717). Patients with metastases confined to LLN had a lower proportion of poor histological types (20.0 % vs. 65.3 %, p = 0.002), lymphatic invasion (20.0 % vs. 59.2 %, p = 0.036) and number of LLN metastases (1.6 vs 2.7, p = 0.004), and all metastases were confined to the internal iliac or obturator region (100.0 % vs. 77.6 %, p = 0.008) compared to patients with both mesenteric and LLN metastasis. ConclusionsApproximately a quarter of patients with rectal cancer have LLN metastases but no mesenteric LN metastases. These patients have favourable pathological features and prognoses and can be managed and treated for mesenteric LN metastasis.

Unilateral Neck Treatment with either Surgery and/or Radiotherapy for Squamous Cell Carcinoma for the Tonsil

Introduction: Strategies for treatment of tonsil carcinoma are under active investigation. Limiting surgical and radiation treatment volumes to the primary tumor and ipsilateral neck in appropriately selected patients are one such approach. Here, we present our institutional experience with treatment through ipsilateral surgical or radiotherapeutic neck management. Methods: We retrospectively reviewed our institutional database of patients with tonsil carcinoma treated from 2012 to 2020. Patients were included for analysis if they received definitive radiation therapy (RT), definitive surgery (S), or surgery with postoperative radiation therapy (S-PORT) and whose treatment volumes were limited to the primary tumor and involved/elective ipsilateral neck. Patients who received radiation and/or surgery to the contralateral neck (including those with bilateral nodal involvement), as well as patients with metastatic disease, were excluded. Clinical factors including T- and N-stage (AJCC 7th edition), and HPV status (by p16 and/or HPV DNA PCR) were recorded, as were pathologic factors (when applicable) including margin status, extracapsular extension (ECE), lymphovascular invasion (LVSI), and perineural invasion (PNI). Overall survival (OS), progression-free survival (PFS), and locoregional control (LRC) at 2 years were estimated using the Kaplan-Meier method. Results: In total, 71 patients were treated with unilateral neck approaches: S (n = 49), RT (n = 10), and S+PORT (n = 12). Among these patients, 32, 36, and 3 had T1, T2, and T3 disease, respectively. N-stage was N0, N1, N2a, N2b, and N3 in 22, 20, 5, 23, and 1 patient(s), respectively. Concurrent chemotherapy was administered in 12 patients. From those with recorded risk factors, 86% were HPV positive, 20% had LVSI, 7% had PNI, 13% had ECE, and 5% had positive margins. From a median follow-up of 27 months, local, regional, and distant failures occurred in 5, 6, and 5 patients, respectively. No contralateral neck failures were recorded. At 2 years, OS, PFS, and LRC were 92% (95% CI 85–99%), 85% (95% CI 75–95%), and 88% (95% CI 80–98%), respectively. Conclusions: In patients with early T-stage tonsil carcinoma, treatment of the primary tumor and ipsilateral neck is associated with acceptable OS, PFS, and LRC. In this population, the risk of contralateral neck failure is likely very low regardless of primary treatment modality. Additional prospective studies are needed to determine the impact of limiting treatment extent, either surgical or radiotherapeutic, to the unilateral neck.

Real-world outcomes of stage II and III colorectal cancers treated by postoperative adjuvant chemotherapy based on the mismatch repair status.

In Japan, immunohistochemistry for mismatch repair (MMR) proteins targeted at stage II and III colorectal cancers (CRCs) has been covered by national insurance since October, 2022. This study aimed to clarify the long-term outcomes of patients with stage II and III CRCs receiving postoperative adjuvant chemotherapy based on their MMR status. The outcomes of 640 patients who underwent radical surgery for stage II and III CRCs were analyzed retrospectively. Deficient MMR (dMMR) was diagnosed in 41 (13.3%) patients with stage II and 28 (9.1%) patients with stage III CRC. The overall survival and recurrence rates were not significantly different between the patients with stage II and those with stage III CRC. The risk factors for recurrence among those with stage II CRC were tumors on the left side, T4 disease, and the presence of BRAF wild type. The recurrence rates were lower in the stage II CRC patients with sporadic dMMR than in those with suspected Lynch syndrome (LS). The first site of recurrence was more frequently the peritoneum or distant lymph node in patients with dMMR. Stage IICRC patients with sporadic dMMR were found to have a very good prognosis. On the other hand, peritoneal dissemination or distant lymph node metastasis tended to develop in patients with dMMR.

FP2.1 - The accuracy of radiological staging in rectal cancer patients post-long course chemoradiotherapy treatment

Abstract Aim Accurate post Long-course chemoradiotherapy treatment (LCCRT) allows safe selection of patients to rectal preservation without delaying resection in those with residual cancer. The aim of this study was to assess the accuracy of radiological staging in these patients. Methods Demographic and treatment data from consecutive patients receiving LCCRT for rectal cancer between May 2020 to December 2021 was collected. Local radiological staging post-LCCRT treatment was compared to pathological staging. Where patients had complete radiological response (CRR) and opted for watch and wait (WW) those with demonstrable local recurrence, within 12 months, were assumed to have been under-staged. Results Of 61 patients, 37 underwent surgical resection following LCCRT and 24 watch and wait for CRR. Post-LCCRT imaging was taken at a median of 10.86 weeks (IQR, 8.86- 13.00) post completion of treatment and resections 16.57 weeks (IQR 9.71 – 23.00) post-imaging. Four WW patients were diagnosed with local recurrence at a median of 56.54 weeks of follow-up (IQR, 39.9 – 67.90). The ratio of patients radiologically staged as T0:T1:T2:T3:T4 was 15%: 0%: 28%: 46%: 10%; whilst the pathology specimens demonstrated 20%: 5%: 12%: 49%: 15% respectively. Nodal staging (N0:N1:N2) was 78%: 20%: 2% with histology showing 71%: 24%: 5% respectively. Conclusion In our low-numbered study T-staging of patients with T0 and T1 disease had highest rates of over-staging such that 2 (5%) patients for potential watch and wait were not recognised as CCR by MRI alone. Nodal staging appeared more accurate although a tendency to under-stage N0 disease was seen.

Diagnostic Performance of MRI and FDG PET/CT for Preoperative Locoregional Staging of Colon Cancer: Systematic Review and Meta-Analysis.

Background: CT is the standard-of-care test for colon cancer (CC) preoperative locoregional staging, but has limited diagnostic performance. More accurate preoperative staging would guide selection among expanding patient-tailored treatment options. Objective: To evaluate the diagnostic performance of MRI for T and N staging and of FDG PET/CT for N staging in CC locoregional staging through systematic review. Evidence Acquisition: PubMed, Embase, and Cochrane Library were searched through December 31, 2023 for studies reporting diagnostic performance of MRI or FDG PET/CT for primary (nonrectal) CC before resection without neoadjuvant therapy using histopathology as reference. Study quality was assessed using the QUADAS-2 tool. Publication bias was assessed with Deeks' funnel plot. Primary outcomes were estimated pooled predictive values, stratified by T and N categories for MRI and N categories for PET/CT. Secondary outcomes were pooled sensitivity and specificity. Evidence Synthesis: The systematic review included 11 MRI studies (686 patients) and five PET/CT studies (408 patients). Thirteen studies had at least one risk of bias or concern of applicability. Deeks' funnel plot asymmetry indicated possible publication bias in MRI studies for differentiation of T3cd-4 from T1-3ab disease and N- from N+ disease. For MRI, for discriminating T1-2 from T3-4 disease, PPV was 64.8% (95% CI [52.9-75.5%]), and NPV was 88.9% (95% CI [82.7-93.7%]); for discriminating T1-3ab from T3cd-4 disease, PPV was 83.4% (95% CI [75.0-90.3%]), and NPV was 74.6% (95% CI [58.2-86.7%]); for discriminating T1-3 from T4 disease, PPV was 94.0% (95% CI [89.4-97.3%]), and NPV was 39.9% (95% CI [24.9-56.6%]); for discriminating N- from N+ disease, PPV was 74.9% (95% CI [69.3-80.0%]), and NPV was 53.9% (95% CI [45.3-62.0%]). For PET/CT, for discriminating N- from N+ disease, PPV was 76.4% (95% CI [67.9-85.1%]), and NPV was 68.2% (95% CI [56.8-78.6%]). Across outcomes, MRI and PET/CT exhibited pooled sensitivity of 55.1-81.4% and pooled specificity of 70.3-88.1%. Conclusion: MRI had strongest predictive performance for T1-2 and T4 disease. MRI and PET/CT had otherwise limited predictive values, sensitivity, and specificity for evaluated outcomes related T and N staging. Clinical Impact: MRI and FDG PET/CT had overall limited utility for preoperative locoregional staging in colon cancer.

Carboplatin and Paclitaxel Chemoradiation for Localized Anal Cancer in Patients Not Eligible for Mitomycin and 5-Fluorouracil.

Although squamous cell carcinoma of the anus (SCCA) is a relatively uncommon malignancy in the United States, it continues to increase in incidence. Treatment for locoregional disease includes mitomycin and 5-fluorouracil with radiation. This combination is associated with significant toxicity, limiting its use in patients who are older or have certain comorbidities. Carboplatin and paclitaxel (C/P) is an accepted treatment regimen for metastatic SCCA. We aim to evaluate the efficacy and toxicity of weekly C/P given with radiation for patients unable to receive standard chemoradiation for SCCA. From our cancer registry, adult patients who received weekly intravenous C/P concurrent with standard-dose radiation for localized SCCA were included in this study. Clinical response was determined based on the evidence of disease on imaging and/or anoscopy. Toxicities were graded according to the CTCAE v5. Ten patients were included; eight were female, and the median age was 75.5 years (54-87). Six had T2 disease, and four had T3 tumors. Four had node-positive disease. The majority (70%) of patients were dosed at standard C (AUC 2) and P (50 mg/m2), with a limited subset requiring dose reduction for baseline performance status. Patients completed a mean of 78.3% (40-100%) of the intended treatments. A total of 89% of the patients achieved a complete clinical response. With a median follow-up of 25.8 months (3.4-50.4 months), 67% of the patients are alive and without recurrence. Two patients have had local recurrence, and one patient had metastatic progression. The most common toxicities of any grade included leukopenia (100%), anemia (100%), radiation dermatitis (100%), diarrhea (100%), and fatigue (100%). Grade 3 or higher toxicities included neutropenic fever (20%), neutropenia (30%), and anemia (30%). This study demonstrates promising tolerability and efficacy for weekly C/P chemoradiation for patients with anal cancer unable to receive mitomycin and 5-fluorouracil. This regimen merits further investigation in prospective clinical trials.

Factors Influencing Outcomes and Survival in Anal Cancer.

We aim to ascertain prognostic factors in the current management of anal cancer within this study. We reviewed the management and outcomes of anal cancer cases over a seven-year period, inclusive (2016-2023). The primary objectives were to assess the demographic characteristics, clinical presentation, and outcomes of all anal cancer patients within our institution. Kaplan-Meier survival analysis was used to estimate survival differences between cohorts, with statistical significance determined using log-rank testing. Cox proportional hazards regression was utilised to identify prognostic factors. Cox regression hazard ratios were reported along with confidence intervals and p-values. The median follow-up time for the study was 29.8 months. Seventy-five patients with anal cancer were included in this study, with 88% (66/75) being squamous cell carcinoma (SCC) and the majority having regional disease (82.7% (62/75)). The median age at diagnosis was 63.4 years (36-94). There was a female preponderance (57.3% (43/75)). In total, 84% (63/75) underwent definitive chemoradiation (dCRT), with 7/63 (11.1%) requiring a salvage abdomino-perineal resection (APR) for residual or recurrent disease. Adverse prognostic indicators include those with T4 disease hazard ratio = 3.81, (95% CI 1.13-12.83, * p = 0.04), poorly differentiated tumour disease HR = 3.37, (95% CI 1.13-10.02, * p = 0.04), having N2 nodal status HR = 5.03, (95% CI 1.11-22.8, * p = 0.04), and having metastatic disease at diagnosis HR = 5.8, (95% CI 1.28-26.42, * p = 0.02). Presenting characteristics including stage, nodal, and differentiation status remain key prognostic indicators in those diagnosed with anal malignancy.

Prevalence of CT-detected extramural vascular invasion in gastric adenocarcinoma and its correlation with other known prognostic factors.

To study the prevalence of extramural vascular invasion (EMVI) in patients with gastric adenocarcinoma (GA) and its association with other prognostic factors. In this retrospective study, consecutive patients with GA who underwent staging CT between January 2021 and December 2022 were included. Two radiologists reviewed the staging CT for EMVI and its grade and documented tumor location, thickness, and TNM stage. Grade 3 and 4 EMVI were reported as ct-EMVI positive and the rest as negative. Similar findings were documented on restaging CT following neoadjuvant chemotherapy (NAC) when available. ct-EMVI was compared with imaging findings on staging and restaging CT, staging laparoscopy findings, peritoneal fluid cytology, and surgical histopathology findings. A total of 191 patients (140 males, 51 females) with a mean age of 53 ± 9years (range 23-93years) were included. 82.2% had poorly differentiated GA and 17.8% had well/moderately differentiated GA. The majority (95.9%) had T3 (n = 34) and T4 (n = 118) disease on baseline CT. The prevalence of ct-EMVI on staging CT was 65% (n = 124), and 34% and 86% among the T3 and T4 GA, respectively. There was a significant association between ct-EMVI and, tumor thickness, tumor extent, ct-T, N, M stages, and especially peritoneal, lymph nodes, and liver metastases and response to NAC (p < 0.05). EMVI is seen commonly in staging CT of advanced gastric cancer patients and is significantly associated with TNM stage, peritoneal metastases, and response to neoadjuvant chemotherapy. Thus, ct-EMVI is a significant prognostic imaging biomarker in GA. IRB min no: 15713.

Clinical course of atypical parathyroid neoplasm with soft tissue extension.

The American Joint Committee on Cancer (AJCC) TNM staging system defines atypical parathyroid neoplasia (APN) as tumor in situ (Tis) and reserves the definition of parathyroid carcinoma (PC) to parathyroid tumor with invasion into surrounding structures. Because the parathyroid gland has no true capsule, "extension" with APN versus microscopic "invasion" of surrounding soft tissue can be difficult and confusing for clinicians. We aimed to determine the clinical course of atypical parathyroid neoplasm with and without soft tissue extension and parathyroid carcinoma with only soft tissue invasion (pT1) and to report the outcomes. Following an IRB-approvedprotocol, we identified all patients treated for parathyroid neoplasm or cancer at our single tertiary care cancer center from 1990 to 2021. We excluded all patients with evidence of clinical or pathologic gross invasion into surrounding structures (pT2 or higher), lymph node involvement, or metastatic disease. By definition, this excluded all cases where the distinction was clinically evident to the surgeon at the time of the operation based on finding a hard, firm, sticky, or discolored parathyroid gland. Only patients with pathologic T1 (pT1) parathyroid carcinoma or APNwere included. All pathologic examinations were independently re-reviewed by a single designated expert senior endocrine pathologist. The definition of APN strictly followed the WHO definition of a clinically worrisome lesion having features including fibrous bands or increased mitotic rate, necrosis, or trabecular growth that did not meet robust criteria for frank invasion. Pathologic T1 disease was defined as invasion limited to soft tissue. Analyses were performed using R version 4.0.2 and Jamovi. Of all PCpatients at our institution, only 71met the strict inclusion criteria of APN or pT1. Forty-four patients had pT1 disease and 27 had APN: 12 of the APN had soft tissue extension, and 15 had no soft tissue extension. The groups were similar with regard to age at diagnosis (p = 0.328). The average follow-up duration was 84 months from initial surgical intervention. Of the 12 with APN, one patient (1/12; 8%) with soft tissue extension recurred, developed distant metastases, and subsequently died during follow up. Of the 44 patients with pT1 PC, six developed distant metastases and 13 (13/44; 30%) died during the follow-up period. One patient with APN and soft tissue extension recurred and died and no patient with APN and no soft tissue extension died. Patients with APN and extension into soft tissue have a clinical course similar to that of APN without soft tissue extension. APN with soft tissue extension is a different disease from pT1 disease with invasion of soft tissue. The pTis classification appears justified for APN with and without soft tissue extension.

Do we need a re-TUR after en bloc resection of T1 stage bladder cancer?

BackgroundA second look trans-urethral resection of the bladder (re-TUR) is recommended after the diagnosis of T1 high grade (T1HG) bladder cancer. Few studies have evaluated the results of re-TUR after a first en bloc resection (EBR) and none of them have specifically reported the pathological results on the field of previous T1 disease.ObjectiveTo report the rate of upstaging and the rate of residual disease (RD) on the field of T1HG lesions resected with EBR.Materials and methodsBetween 01/2014 and 06/2022, patients from 2 centers who had a re-TUR after an EBR for T1HG urothelial carcinoma were retrospectively included. Primary endpoint was the rate of RD including the rate of upstaging to T2 disease on the scar of the primary resection. Secondary endpoints were the rate of any residual disease outside the field.ResultsSeventy-five patients were included. No muscle invasive bladder cancer lesions were found after re-TUR. Among the 16 patients who had a RD, 4 were on the resection scar. All of these lesions were papillary and high grade. RD outside the field of the first EBR was observed in 12 patients.ConclusionAfter EBR of T1HG disease, none of our patients had an upstaging to MIBC. However, the rate of RD either on and outside the field of the EBR remains quite significant. We suggested that predictive factors of residual papillary disease (number of tumors at the initial TUR and concomitant CIS) might be suitable to select patient who will benefit of the re-TUR.

Association between warfarin and survival in invasive melanoma: a population-based cohort study

BackgroundWarfarin has been shown to reduce cancer risk via Vitamin K related AXL tyrosine kinase inhibition. Although AXL has been implicated in disease progression and therapy resistance in preclinical melanoma models, there are no clinical studies evaluating the impact of warfarin on melanoma prognosis. Hence, we sought to evaluate the relationship between warfarin and survival in melanoma. MethodsWe conducted a retrospective population-based cohort study of melanoma patients aged ≥ 65 years diagnosed between 2009–2013 from the Surveillance, Epidemiology, and End Results-Medicare database. Patients were grouped according to warfarin therapy 6 months prior and after melanoma diagnosis. Univariable and multivariable Cox proportional hazards models were used to compare overall (OS) and melanoma-specific survival (MSS) between groups. ResultsOverall, 10,778 patients with invasive melanoma were included. 13.2 % were prescribed warfarin, with atrial fibrillation being the most common indication (74.1 %). Warfarin prescription was associated with older age, male sex, and a greater number of comorbidities (all p < 0.001). Patients prescribed warfarin more frequently presented with ulceration, T3 and T4 disease, and stage II disease (all p < 0.05). Warfarin prescription was associated with greater MSS and OS in multivariable models (MSS adjusted hazard ratio [aHR] 0.72, 95 % CI 0.54–0.96, p = 0.02; OS aHR 0.88, 95 % CI 0.79–0.99, p = 0.04). ConclusionsWarfarin was associated with greater MSS and OS among melanoma patients. These findings highlight the potential for Vitamin K related pathways to impact cancer specific activity. Further study of AXL and Vitamin K inhibition will be of significant interest in melanoma, targeted strategies actively under investigation.

Factors associated with total laryngectomy following organ-preserving treatment of laryngeal SCC.

A subset of laryngeal squamous cell carcinoma (LSCC) patients undergoing larynx preserving treatment ultimately require total laryngectomy (TL) for oncologic or functional reasons. This study aims to identify TL risk factors in these patients. Retrospective cohort study using Veterans Affairs (VA) database. T1-T4 LSCC cases treated with primary radiotherapy (XRT) or chemoradiotherapy (CRT) were assessed for TL and recurrence. Binary logistic and Cox regression and Kaplan-Meier analyses were implemented. Of 5390 cases, 863 (16.0%) underwent TL. On multivariable analysis, age (adjusted odds ratio: 0.97 [0.96-0.98]; p < .001) and N3 disease (0.42 [0.18-1.00]; p = .050) were associated with reduced risk of TL, whereas current alcohol use (1.22 [1.04-1.43]; p = .015) and >T1 disease (T2, 1.76 [1.44-2.17]; p < .001; T3, 2.06 [1.58-2.68]; p < .001; T4, 1.79 [1.26-2.53]; p = .001) were associated with increased risk of TL. However, N2 (adjusted hazard ratio: 1.30 [1.10-1.55]; p = .003) and N3 (2.02 [1.25-3.26]; p = .004) disease were associated with an increased risk for local recurrence. Compared to XRT, treatment with CRT was associated with reduced risk for local recurrence after adjusting for other factors (0.84 [0.70-0.99]; p = .044). Those who do not receive TL following local recurrence have poorer disease-specific survival (log-rank, p < .001). In patients without local recurrence, N2 disease was associated with a fourfold increase in risk of TL (4.24 [1.83-9.82]; p < .001). Advanced nodal stage was associated with reduced rates of salvage TL in the setting of local recurrence, and subsequent worse prognosis after recurrence. Conversely, advanced nodal stage may increase the risk for functional salvage TL in patients without recurrence. Level 3.

Image directed redesign of bladder cancer treatment pathways: the BladderPath RCT.

Transurethral resection of bladder tumour has been the mainstay of bladder cancer staging for >60 years. Staging inaccuracies are commonplace, leading to delayed treatment of muscle-invasive bladder cancer. Multiparametric magnetic resonance imaging offers rapid, accurate and non-invasive staging of muscle-invasive bladder cancer, potentially reducing delays to radical treatment. To assess the feasibility and efficacy of the introducing multiparametric magnetic resonance imaging ahead of transurethral resection of bladder tumour in the staging of suspected muscle-invasive bladder cancer. Open-label, multistage randomised controlled study in three parts: feasibility, intermediate and final clinical stages. The COVID pandemic prevented completion of the final stage. Fifteen UK hospitals. Newly diagnosed bladder cancer patients of age≥18 years. Participants were randomised to Pathway 1 or 2 following visual assessment of the suspicion of non-muscle-invasive bladder cancer or muscle-invasive bladder cancer at the time of outpatient cystoscopy, based upon a 5-point Likert scale: Likert 1-2 tumours considered probable non-muscle-invasive bladder cancer; Likert 3-5 possible muscle-invasive bladder cancer. In Pathway 1, all participants underwent transurethral resection of bladder tumour. In Pathway 2, probable non-muscle-invasive bladder cancer participants underwent transurethral resection of bladder tumour, and possible muscle-invasive bladder cancer participants underwent initial multiparametric magnetic resonance imaging. Subsequent therapy was determined by the treating team and could include transurethral resection of bladder tumour. Feasibility stage: proportion with possible muscle-invasive bladder cancer randomised to Pathway 2 which correctly followed the protocol. Intermediate stage: time to correct treatment for muscle-invasive bladder cancer. Between 31 May 2018 and 31 December 2021, of 638 patients approached, 143 participants were randomised; 52.1% were deemed as possible muscle-invasive bladder cancer and 47.9% probable non-muscle-invasive bladder cancer. Feasibility stage: 36/39 [92% (95% confidence interval 79 to 98%)] muscle-invasive bladder cancer participants followed the correct treatment by pathway. Intermediate stage: median time to correct treatment was 98 (95% confidence interval 72 to 125) days for Pathway 1 versus 53 (95% confidence interval 20 to 89) days for Pathway 2 [hazard ratio 2.9 (95% confidence interval 1.0 to 8.1)], p = 0.040. Median time to correct treatment for all participants was 37 days for Pathway 1 and 25 days for Pathway 2 [hazard ratio 1.4 (95% confidence interval 0.9 to 2.0)]. For participants who underwent chemotherapy, radiotherapy or palliation for multiparametric magnetic resonance imaging-diagnosed stage T2 or higher disease, it was impossible to conclusively know whether these were correct treatments due to the absence of histopathologically confirmed muscle invasion, this being confirmed radiologically in these cases. All patients had histological confirmation of their cancers. Due to the COVID-19 pandemic, we were unable to realise the final stage. The multiparametric magnetic resonance imaging-directed pathway led to a substantial 45-day reduction in time to correct treatment for muscle-invasive bladder cancer, without detriment to non-muscle-invasive bladder cancer participants. Consideration should be given to the incorporation of multiparametric magnetic resonance imaging ahead of transurethral resection of bladder tumour into the standard pathway for all patients with suspected muscle-invasive bladder cancer. The improved decision-making accelerated time to treatment, even though many patients subsequently needed transurethral resection of bladder tumour. A proportion of patients can avoid transurethral resection of bladder tumour completely, reducing costs and morbidity, given the much lower cost of magnetic resonance imaging and biopsy compared to transurethral resection of bladder tumour. Further work to cross-correlate with the recently developed Vesical Imaging-Reporting and Data System will improve accuracy and aid dissemination. Longer follow-up to examine the effect of the pathway on outcomes is also required. Incorporation of liquid deoxyribonucleic acid-based biomarkers may further improve the quality of decision-making and should also be investigated further. This study is registered as ISRCTN 35296862. This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR135775) and is published in full in Health Technology Assessment; Vol. 28, No. 42. See the NIHR Funding and Awards website for further award information.

Local Therapy and Reconstruction in Penile Cancer: A Review.

Local therapy for penile cancer provides robust survival and can preserve the penis functionally and cosmetically. Interventions must target the appropriate clinical stage. We reviewed studies regarding the primary therapy in penile cancer, from topical therapy to radical penectomy, and reconstructive techniques. Topical therapy (5-FU or Imiquimod) provides a robust oncologic response in patients with Ta or Tis disease. Multiple laser therapies are available for localized patients and those with low-grade T1 disease. There is a non-trivial risk of progression and nodal metastases in poorly selected patients. Wide local excision provides an oncologically sound option in patient with up to T1 disease; less evidence exists for Mohs microsurgery in the setting of penile cancer. Increasingly aggressive approaches include glansectomy and partial/radical penectomy, which provide 5- and 10-year cancer-specific survival rates of over 80%. Meticulous reconstruction is necessary for the durable function of the remaining penis. Preservation of voiding and sexual function occurs via penile skin grafting, glans resurfacing, creation of a functional penile stump, and phalloplasty with a penile implant. Perineal urethrostomy provides an alternative in pathology demanding extensive partial or radical penectomy, and a durable option for seated voiding. Clinical suspicion and timely diagnosis are paramount in terms of management as less-invasive options for earlier-stage disease develop.

Outcomes of Resectable Gallbladder Cancer: A Retrospective Analysis From a Tertiary Care Centre in India.

Background Gallbladder carcinoma (GBC) has deleterious outcomes, but due to its reduced incidence in Western countries, there is a paucity of data on this disease. Here we report the outcomes of a retrospective analysis of resectable gallbladder cancer from a tertiary cancer centre in eastern India. The primary objective of this study is to evaluate the overall survival (OS) and relapse-free survival (RFS) rates among patients with resectable GBC. Methods A retrospective analysis was carried out on patients who underwent radical surgery between 2007 and 2022 and received various neoadjuvant and adjuvant chemotherapy methods. Patients who had adjuvant chemoradiotherapy concurrently or who did not receive adjuvant therapy were excluded. All the baseline clinicopathological characteristics were retrieved from electronic medical records. The survival data were collected from records of follow-up visits as well as telephonic calls to the patients who were lost to follow-up. Simple proportions were used for baseline characteristics, and the Kaplan-Meier method was used for survival analysis. Results A total of 161 patients were identified, and data were captured from electronic medical records. The included patients' ages ranged between 26 and 80 years, with a median age of 56 years. Among the participants, 103 were female (64%) and 58 (36%) were male. Among the 161 patients, the median number of lymph nodes harvested was nine (ranging from one to 43), and only three patients were margin-positive. The tumour, nodes, and metastasis (TNM) distributions were as follows: pT2 in 111 patients (70.25%), pT3 in 44 patients (27.85%), and pT4 in three patients (1.90%). The nodal statuses were pN0 in 91 patients (61.9%), pN1 in 51 patients (34.69%), and pN2 in five patients (3.4%). The majority (64%) received single-agent capecitabine, 27% received gemcitabine-based platinum doublet therapy, and 4.3% received neoadjuvant therapy. Of the full sample, 2.4% received concurrent adjuvant chemo plus radiation therapy, and three patients did not receive any adjuvant therapy. Additionally, among the 161 patients, 34.16% had a relapse, with 47% being local and 52% being distant relapses. The median follow-up was 49 months (interquartile range (IQR) 23-71 months). The 24-month RFS rate was 67.1% (SD+/- 4.3%), and the 24-month OS rate was 78.1% (SD+/- 4.1%). Conclusion Our data, which is from one of the largest samples from India, show that resectable gallbladder cancer has very good outcomes after radical surgery and adjuvant chemotherapy. There was a higher proportion of T2 and node-negative disease, which could have led to better survival compared to published literature.

The influence of socioeconomic disadvantage on short- and long-term outcomes after oesophagectomy for cancer: an Australian multicentre study.

Socioeconomic status (SES) affects outcomes following surgery for various cancers. There are currently no Australian studies that examine the role of socioeconomic disadvantage on outcomes following oesophagectomy for cancer. This study assessed whether SES was associated with short-term perioperative morbidity, long-term survival, and oncological outcomes following oesophagectomy across three tertiary oesophageal cancer centres in Australia. A retrospective cohort study was performed comprising all patients who underwent oesophagectomy for cancer across three Australian centres. Patients were stratified into SES groups using the Index of Relative Socioeconomic Advantage and Disadvantage (IRSAD). Outcomes measured included perioperative complication rates, overall survival, and disease-free survival. The study cohort was 462 patients, 205 in the lower SES and 257 in the higher SES groups. The lower SES group presented with more advanced oesophageal cancer stage, a higher rate of T3 (52.6% versus 42.7%, P = 0.038) and N2 disease (19.6% versus 10.5%, P = 0.006), and had a higher rate of readmission within 30 days (11.2% versus 5.4%, P = 0.023). There was no difference in overall survival or disease-free survival between groups. Lower socioeconomic status was associated with more advanced stage and increased risk of early, unplanned readmission following oesophagectomy, but was not associated with a difference in overall or disease-free survival.