pT2 N0 Research Articles

Initial negative resection margin versus revised negative resection margin in patients who underwent surgery without adjuvant therapy for early-stage oral tongue squamous cell carcinoma

BackgroundIn cases of positive resection margin (RM), re-resection is generally recommended. There has been controversy about the oncologic impact of revised negative RMs after re-resection. The aim of this study was to investigate the oncologic impact of revised negative RM in patients who underwent surgery without adjuvant therapy for early-stage (pT1-2/N0) oral tongue squamous cell carcinoma (OSCC). MethodsWe retrospectively analyzed patients with pT1-2 N0 OSCC who did not receive adjuvant therapy (N=441). These patients were classified into an initial negative RM (R0, n = 380) group and a revised negative RM (R1-R0, n = 61) group. Demographic and clinical data (T stage, tumor length, depth of invasion [DOI], lymphovascular invasion [LVI], perineural invasion [PNI], and recurrence) were compared between the R0 and R1-R0 groups. ResultsAge, sex, T stage, DOI, LVI, PNI, and SUVmax were not significantly different between the two groups. Local recurrence was more frequent (P=0.045) in the R1-R0 group (13.1 %) than in the R0 group (5.5 %). Local recurrence-free survival was better in the R0 group than in the R1-R0 group (P=0.046). There was no significant difference in overall recurrence or overall survival. On multivariate analysis, initial positive RM was the independent significant risk factor (hazard ratio, 2.249; 95 % confidence interval, 1.025–4.935; P=0.043) for local recurrence. ConclusionA revised clear RM after initial cut-through margin is a risk factor for local recurrence in early-stage OSCC. Cautious should be considered in early-stage OSCC patients with revised clear RM.

45 INTerpath-004: A phase 2, randomized, double-blind study of pembrolizumab with V940 (mRNA-4157) or placebo in the adjuvant treatment of renal cell carcinoma

Abstract Background The PD-1 inhibitor pembrolizumab is approved as monotherapy for the adjuvant treatment of patients with renal cell carcinoma (RCC) who are at increased risk of recurrence following nephrectomy or nephrectomy and resection of metastatic lesions based on results from the phase 3 KEYNOTE-564 trial. Novel combination strategies could provide further clinical benefit in the adjuvant setting. V940 (mRNA-4157) is an individualized neoantigen therapy that is hypothesized to increase the antitumor activity of T cells and enhance the activity of pembrolizumab. V940 plus pembrolizumab showed improved clinical outcomes for stage III/IV melanoma compared with pembrolizumab alone in the phase 2b KEYNOTE-942 study. INTerpath-004 is a global, multicenter, randomized, double-blind, phase 2 trial (NCT06307431) designed to evaluate the efficacy and safety of adjuvant pembrolizumab with V940 or placebo in patients with RCC who have undergone nephrectomy. Methods Eligible patients are adults with histologically or cytologically confirmed RCC with clear cell or papillary histology (intermediate-high risk [pT2 Gr4, N0, M0 or pT3 Gr3/4, N0, M0], high-risk [pT4, N0, M0 or pT any stage, N1, M0], or M1 NED [solid, isolated, soft tissue metastases that can be completely resected at the time of nephrectomy or ≤2 years from nephrectomy]) with or without sarcomatoid features. Patients must have undergone nephrectomy and/or metastasectomy ≤12 weeks prior to randomization and be tumor-free as assessed by investigator. Patients must not have received prior systemic therapy ≤4 weeks or radiotherapy ≤2 weeks prior to randomization. Approximately 272 patients will be randomly assigned 1:1 to receive pembrolizumab 400 mg intravenously every 6 weeks for up to 9 cycles in combination with either V940 1 mg or placebo intramuscularly every 3 weeks for up to 9 doses or treatment discontinuation due to unacceptable toxicity, disease recurrence, patient withdrawal, or investigator decision. Randomization will be stratified by histology (clear cell vs papillary) and disease risk (intermediate-high vs high vs M1 NED). Imaging assessments (computed tomography or magnetic resonance imagery) will be performed every 12 weeks through year 2, every 16 weeks in years 3-5, and every 24 weeks in year 6 and beyond. The primary endpoint is disease-free survival by investigator assessment. Secondary endpoints include distant metastasis-free survival, overall survival, and safety parameters including adverse events (AEs), laboratory test results, and vital signs. AEs will be monitored throughout the study and for 30 days after the last dose of treatment (90 for serious AEs) and graded per National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. Efficacy will be assessed in all randomly assigned patients, and safety will be assessed in all patients who received ≥1 dose of study intervention. Recruitment is ongoing.

Survival results according to Oncotype Dx recurrence score in patients with hormone receptor positive HER-2 negative early-stage breast cancer: first multicenter Oncotype Dx recurrence score survival data of Turkey.

The Oncotype Dx recurrence score (ODx-RS) guides the adjuvant chemotherapy decision-making process for patients with early-stage hormone receptor-positive, HER-2 receptor-negative breast cancer. This study aimed to evaluate survival and its correlation with ODx-RS in pT1-2, N0-N1mic patients treated with adjuvant therapy based on tumor board decisions. Estrogen-positive HER-2 negative early-stage breast cancer patients (pT1-2 N0, N1mic) with known ODx-RS, operated on between 2010 and 2014, were included in this study. The primary aim was to evaluate 5-year disease-free survival (DFS) rates according to ODX-RS. A total of 203 eligible patients were included in the study, with a median age of 48 (range 26-75) and median follow-up of 84 (range 23-138) months. ROC curve analysis for all patients revealed a recurrence cut-off age of 45 years, prompting evaluation by grouping patients as ≤45 years vs. >45 years. No significant difference in five-year DFS rates was observed between the endocrine-only (ET) and chemo-endocrine (CE) groups. However, among the ET group, DFS was higher in patients over 45 years compared to those aged ≤45 years. When stratifying by ODx-RS as 0-17 and ≥18, DFS was significantly higher in the former group within the ET group. However, such differences were not seen in the CE group. In the ET group, an ODx-RS ≥18 and menopausal status were identified as independent factors affecting survival, with only an ODx-RS ≥18 impacting DFS in patients aged ≤45 years. The ROC curve analysis for this subgroup found the ODx-RS cut-off to be 18. This first multicenter Oncotype Dx survival analysis in Turkey demonstrates the importance of Oncotype Dx recurrence score and age in determining treatment strategies for early-stage breast cancer patients. As a different aproach to the literature, our findings suggest that the addition of chemotherapy to endocrine therapy in young patients (≤45 years) with Oncotype Dx recurrence scores of ≥18 improves DFS.

Role of Adjuvant Chemotherapy in Early-Stage Combined Small Cell Lung Cancer

BackgroundThe role of adjuvant therapy in completely resected primary tumors that have components of both non–small cell lung cancer and small cell lung cancer (combined SCLC) is poorly understood. We sought to determine the potential benefits of adjuvant chemotherapy in patients who undergo complete resection for early-stage combined SCLC. MethodsOverall survival of patients with pathologic T1-2 N0 M0 combined SCLC who underwent complete resection in the National Cancer Database from 2004 to 2017, stratified by adjuvant chemotherapy vs surgery alone, was evaluated by multivariable Cox proportional hazards modeling and propensity score–matched analysis. Patients treated with induction therapy and those who died within 90 days of surgery were excluded from analysis. ResultsOf 630 patients who had pT1-2 N0 M0 combined SCLC during the study period, 297 patients (47%) underwent complete R0 resection. Adjuvant chemotherapy was administered to 63% of patients (n = 188), and 37% of patients underwent surgery alone (n = 109). In unadjusted analysis, the 5-year overall survival was 61.6% (95% CI, 50.8-70.7) for patients who underwent surgery alone and 66.4% (95% CI, 58.4-73.3) for patients who underwent adjuvant chemotherapy. In multivariable and propensity score–matched analysis, there were no significant differences in overall survival between adjuvant chemotherapy and surgery alone (adjusted hazard ratio, 1.16; 95% CI, 0.73-1.84). These findings were consistent when limited to patients who underwent lobectomies or to healthier patients who have at most 1 major comorbidity. ConclusionsIn this national analysis, patients with pT1-2 N0 M0 combined SCLC treated with surgical resection alone have similar outcomes to those who undergo adjuvant chemotherapy.

Pregnancy in a Young Patient with Metastatic HER2-Positive Breast Cancer—Between Fear of Recurrence and Desire to Procreate

Breast cancer is the most frequent neoplasm among women and the second leading cause of death by cancer. It is the most frequent cancer diagnosed during pregnancy. Pregnancy-associated breast cancer is defined as breast cancer that is diagnosed during pregnancy and/or in the postpartum period. Data about young women with metastatic HER2-positive cancer who desire a pregnancy are scarce. The medical attitude in these clinical situations is difficult and nonstandardized. We present the case of a 31-year-old premenopausal woman diagnosed in December 2016 with a stage IV Luminal HER2-positive metastatic breast cancer (pT2 N0 M1 hep). The patient was initially treated by surgery in a conservative manner. Postoperatively, the presence of liver metastases was found by CT investigation. Consequently, line I treatment (docetaxel l75 mg/m² iv; trastuzumab 600 mg/5 mL sq) and ovarian drug suppression (Goserelin 3.6 mg sq at 28 days) was administered. After nine cycles of treatment, the patient's liver metastases had a partial response to the therapy. Despite having a favorable disease evolution and a strong desire to procreate, the patient vehemently refused to continue any oncological treatment. The psychiatric consult highlighted an anxious and depressive reaction for which individual and couple psychotherapy sessions were recommended. After 10 months from the interruption of the oncological treatment, the patient appeared with an evolving pregnancy of 15 weeks. An abdominal ultrasound revealed the presence of multiple liver metastases. Knowing all the possible effects, the patient consciously decided to postpone the proposed second-line treatment. In August 2018, the patient was admitted in the emergency department with malaise, diffuse abdominal pain and hepatic failure. Abdominal ultrasound found a 21-week-old pregnancy which had stopped in evolution, multiple liver metastases and ascites in large quantity. She was transferred to the ICU department where she perished just a few hours later. Conclusions/Discussion: From a psychological standpoint, the patient had an emotional hardship to make the transition from the status of a healthy person to the status of a sick person. Consequently, she entered a process of emotional protection of the positive cognitive distortion type, which favored the decision to abandon treatment and try to complete the pregnancy to the detriment of her own survival. The patient delayed the initiation of oncological treatment in pregnancy until it was too late. The consequence of this delay in treatment led to the death of the mother and fetus. A multidisciplinary team worked to provide this patient with the best medical care and psychological assistance throughout the course of the disease.

HPB P60 Pancreatic Carcinosarcoma as a rare cause of upper gastrointestinal bleeding requiring resection

Abstract Background Pancreatic carcinosarcoma is a rare malignant neoplasm and has a very poor prognosis. Diagnosis is mainly by pathological examination including immunohistochemistry (IHC) of the biopsy or resected specimen. Due to the rarity of the cancer, information regarding clinical presentation, pathology and management is limit to a few case reports. Methods We report a 61-year-old fit and healthy male, who presented to the emergency department with melaena and syncope. Initial CT scan showed a pancreatic body/tail tumour, likely pancreatic cancer without nodal or intra-abdominal metastasis. Upper GI endoscopy revealed a lesion in the second part of the duodenum, with a visible vessel, and evidence of recent bleeding . Two clips were applied, and a biopsy of the lesion showed ulcer slough only. Tumour markers and IgG4 levels were normal. An MRI pancreas showed no definite pancreatic mass, features of chronic pancreatitis and irregular bile ducts. HPB MDT consensus was to proceed for EUS, which confirmed a hypoechoic, vascular, 3cm mass lesion in D1-D2. Biopsies again, showed ulcer slough. A PET CT scan showed avidity in the second part of the duodenum and pancreatic head, neck and distal body. The patient presented to the surgical emergency unit twice during this time with symptoms of anaemia requiring IV iron and blood transfusions, and with early signs of obstruction, which settled with conservative management. Interval MRI showed increase in size of the duodenal mass, and stable appearance of the lesion in the head of the pancreas. Eventually, semi-emergency total pancreaticoduodenectomy and splenectomy was undertaken. Results Intraoperatively, a large D2 tumour was found extending into the pancreatic head posteriorly, compressing but not infiltrating the IVC. The rest of the pancreas was hard in consistency and nodular. Soft lymph nodes were found at the aorto-caval, common hepatic and around the SMA. There was no obvious intra-abdominal metastasis. The final histopathology showed a malignant, biphasic tumour favouring pancreatic carcinosarcoma staged pT3 N0 (0/29) L1 V1 R1 (posterior and SMV). On molecular cytogenetic analysis there was no evidence of rearrangement associated with synovial sarcoma in the cells examined. He recovered well post operatively and has commenced adjuvant chemotherapy of modified Folfirinox. Conclusions Pancreatic carcinosarcoma is a rare entity, which due to its unusual presentation, can be challenging to manage. Prompt MDT discussion is instrumental in such cases. The assessment of different radiological modalities, showing progressive increase in the size of the lesion within a short time period, raised the suspicion of an aggressive mitotic lesion, with the repeat biopsies unlikely to yield diagnosis in an otherwise operable lesion. Ultimately, the patient underwent a semi-emergency, total pancreaticoduodenectomy and splenectomy due to ongoing bleeding and the rapidly growing tumour size. In this case, surgery followed by adjuvant chemotherapy has been adopted as the optimum management strategy, for both bleeding control, and oncological benefit.

S2029 Epiploic Appendagitis: A Red Herring?

Introduction: Epiploic appendagitis (EA) is a rare cause of acute abdominal pain that has a relatively benign course. The importance of identifying EA as a clinical mimicker is crucial to avoid unnecessary hospitalizations, antibiotic use, and surgery. Although no trigger has been established as a cause for EA, it is hypothesized that systemic inflammation can lead to an EA attack. Case Description/Methods: A 43-year-old White female with no significant GI history presented with 2 days of sudden onset, sharp, non-radiating, worsening left lower quadrant (LLQ) with nausea. Initial blood work was unremarkable. CT abdomen revealed a hyper-attenuating ring lesion along the anti-mesenteric margin adjacent to the distal descending colon, along with mesenteric lymph nodes consistent with epiploic appendagitis. She was managed conservatively with complete resolution of symptoms. A few years later, she presented again, with similar abdominal complaints. Repeat abdominal imaging showed recurrence of EA in the same location. Few shotty mesenteric lymph nodes were identified. She was treated conservatively for EA. A few more years passed, and she now had another episode of recurrent LLQ pain, CT abdomen showed findings consistent with EA along with a short segment of mural thickening and mild hyper-enhancement in the mid descending colon. Colonoscopy revealed a large circumferential mass in the sigmoid colon with an apple core lesion in the proximal sigmoid colon with luminal narrowing. Biopsy revealed an adenocarcinoma. No lymph node involvement was noted. As the TNM staging was pT3 N0 M0, she underwent a sigmoidectomy with left colon and rectal end-to-end anastomosis (Figure). Discussion: Epiploic appendages are fat-filled serosal outpouchings of the colonic surface. They are connected to the colon by a vascular stalk. Acute epiploic appendagitis is theorized to be caused by torsion, underlying inflammation, or venous occlusion of the appendage. CT scan is the gold standard for diagnosing EA and helps rule out other intra-abdominal pathologies. Recurrent and persistent EA is very rare and may mask an underlying occult abdominal pathology. There have not been any reported cases of CRC that are associated with and possibly trigger EA. In patients with recurrent EA, after common causes of acute abdominal pain are ruled out, evaluation for intestinal/intraluminal pathologies, especially colorectal malignancy should be considered as they are not readily apparent on CT scans.Figure 1.: A: Red arrow showing an inflamed epiploic appendage during initial presentations. B: Red arrow showing epiploic appendagitis. Green arrow with colonic wall thickening in the descending colon, with adjacent EA. 3: Colonoscopy showing the large friable mass in the sigmoid colon.

S2078 Multicentric, Synchronous Colon Cancer in the Rectum, Sigmoid and Cecum in an Elderly Female

Introduction: Multicentric tumors are more common in genetically-linked cancers. In most instances, tumor occurrence in a different location is due to recurrence of the malignancy. Our case illustrates a rare endoscopic finding of 3 distinct and synchronous adenocarcinomas of the rectum, sigmoid colon, and cecum in an otherwise healthy elderly female at an average risk for colorectal cancer. Case Description/Methods: An 81-year-old female with no medical history presented to the hospital with constipation and diffuse intermittent abdominal pain for 4 months. She had been self-medicating at home with over-the-counter laxatives but recently reported that she was not experiencing relief. She denied any prior endoscopy or family history of colorectal cancer. On admission, her vital signs were normal and her physical exam was significant for diffuse abdominal tenderness to palpation. Digital rectal examination revealed a non-tender, hard mass in the left lateral wall of the rectum. Her complete blood count and comprehensive metabolic panels were normal. Iron studies were also unremarkable. A computed tomography (CT) scan of the abdomen and pelvis showed thickening in the sigmoid colon and the rectum with scattered subcentimeter lymph nodes. On colonoscopy, she was found to have 3 partially-obstructing, malignant-appearing lesions located in the rectum, proximal sigmoid, and cecum. Biopsies of all 3 sites revealed adenocarcinoma. Immunohistochemistry for DNA mismatch repair proteins (MMR) showed intact MLH1, MSH2, MSH6, PMS2 genes. She underwent a laparoscopic total colectomy with end ileostomy, with pathological staging revealing pT3 N0 for the sigmoid tumor and pT4a N2b for the cecal tumor. She was planned for neoadjuvant chemoradiation therapy in anticipation for future robotic proctectomy for treatment of the rectal tumor (Figure 1). Discussion: Synchronous colorectal cancers pose a distinct challenge in terms of management and treatment. The extent of surgical resection and the use of chemoradiation depends on the location, number of lesions, and lymph node involvement. Our patient was an interesting case as she presented later in life and her only symptom was constipation. She was an average risk patient, had otherwise normal labs, and HNPCC/lynch syndrome-related cancers were excluded on the basis of normal immunohistochemistry testing.Figure 1.: Partially-obstructing malignant lesions in the (A) rectum, (B) proximal sigmoid, and (C) cecum.

Variation in recurrence rate and overall survival (OS) outcomes by disease stage and incremental impact of time to recurrence on OS in localized renal cell carcinoma (RCC).

4543 Background: Prior research shows that post-nephrectomy recurrence is correlated with significantly increased mortality in patients (pts) with intermediate-high (int-high) risk and high risk RCC. However, no study has quantified the incremental OS associated with increased time to recurrence (ToR). Additionally, limited evidence is presented on the variation of recurrence rate and OS by stage of RCC. Methods: The SEER-Medicare database (2007–2016) was used in this retrospective observational study. Post-nephrectomy pts with newly diagnosed, int-high risk (pT2 N0 high grade, pT3 N0 any grade) or high-risk (pT4 N0 any grade, pT any N1 any grade) RCC were identified and stratified based on tumor stage and grade. Grade was defined based on Furhman grading system and was reported in SEER Registry. Post-nephrectomy recurrence free rates and OS by disease stage were described using Kaplan-Meier analyses. OS from nephrectomy in pts with recurrence vs pts without recurrence was compared by disease stage. Multivariable regression analysis was used to quantify the incremental OS associated with increased ToR post-nephrectomy in all pts with recurrence. Results: 643 pts met the inclusion criteria (269 with vs 374 without recurrence; median follow-up: 23 months). The mean age was 75.5 years (yrs), 61% male, and 86% white. Results presented in the table showed wide variance in 5-yr recurrence-free rate in int-high risk group (28%-63%) and indicated substantial risk of disease recurrence in all subgroups of int-high risk pts. Among those with T3 Grade 1-2, T3 Grade 3, and T3 Grade 4 disease, pts with recurrence had significantly higher risk of death than those without (all ps<0.05;). Results for pts with T2 and T4 disease were not presented due to small sample size. Multivariable regression analysis indicated that 1 additional yr of ToR was associated with 0.73 additional yrs (8.8 additional months) of OS post nephrectomy (95% CI: 0.40, 1.05 yrs; p<0.001). Conclusions: The non-trivial recurrence rates observed in pts with T3 Grade 1-2 and T3 Grade 3 RCC highlighted the substantial risk of recurrence and unmet needs in the int-high risk RCC patients. This study also confirms the incremental nature of the association of ToR and OS in patients with int-high and high risk localized RCC. These findings highlight the need for effective early intervention with adjuvant treatments in int-high and high risk post-nephrectomy RCC pts. [Table: see text]

Lobectomy offers improved survival outcomes relative to segmentectomy for >2 but ≤4 cm non–small cell lung cancer tumors

ObjectiveThe objective was to compare overall survival (OS) between lobectomy and segmentectomy for patients with non–small cell lung cancers (NSCLCs) > 2 but ≤4 cm. MethodsThe National Cancer Database was queried to identify treatment-naïve patients with NSCLC tumors >2 but ≤4 cm. Eligible patients were diagnosed with pT1 or T2 N0 M0 disease, underwent lobectomy or segmentectomy, and received no adjuvant therapy. OS was compared using the Kaplan-Meier method, and the Cox proportional-hazards model was used to identify prognostic factors for death. Propensity score matching was performed to minimize the effects of potential confounders. ResultsIncluded were 32,792 patients: lobectomy (n = 31,353) and segmentectomy (n = 1439). Five-year OS was improved following lobectomy over segmentectomy for patients with >2 but ≤4 cm NSCLCs (62.3% vs 52.6%; P < .0001). Further stratification demonstrated improved 5-year OS following lobectomy over segmentectomy: >2 but ≤3 cm (64.9% vs 54.3%; P < .0001) and >3 but ≤4 cm (56.9% vs 47.6%; P = .0003). In patients with a Charlson-Deyo comorbidity index of 0, 5-year OS was greater following lobectomy for >2 but ≤4 cm tumors (67.1% vs 62.1%; P = .03). Further stratification demonstrated improved 5-year OS following lobectomy for patients with Charlson-Deyo comorbidity index of 0 and > 3 but ≤4 cm tumors (61.8% vs 54.6%; P = .02). Segmentectomy was prognostic for increased risk of death in the year 1 through 5 postoperative period (hazard ratio, 1.35; P < .0001). Five-year OS remained greater following lobectomy after propensity score matching (59.6% vs 52.7%; P = .02). ConclusionsLobectomy is associated with superior 5-year OS compared with segmentectomy and may be preferred for NSCLC tumors >2 but ≤4 cm when feasible.

Primary Squamous Cell Carcinoma of the Thyroid Gland

Primary squamous cell carcinoma of the thyroid gland (ThSCC) is extremely rare. It accounts for less than 1% of thyroid malignancies with an aggressive behavior and poor prognosis. We report a case of an early stage ThSCC revealed through the histopathological findings of a total thyroidectomy for a non-toxic multinodular goiter. A 49 years old women presented with two years history of nodular goiter. Ultrasonography confirmed an enlarged thyroid gland with multiple nodules, one was ranked EU-TIRADS V without enlarged cervical lymph nodes. The patient underwent total thyroidectomy. Per operative exploration found few enlarged central lymph nodes that were harvested. Pathology examination found SCC proliferating in the thyroid gland staged pT3 N0. The patient received an adjuvant radiotherapy. Post treatment course is uneventful after one year follow up. Although there is a large agreement regarding the management of advanced ThSCC stage, the management of early stage disease is still controversial.

AB008. Synchronous thymic and breast malignancies: a single institutional experience

: Breast cancer is the most frequent neoplasm in female population. Conversely, thymic epithelial tumors (TETs) are rare diseases, often discovered in late stages. TET patients have a high risk of developing secondary malignancies compared with general population, with an incidence rate from 8 to 31%. We recently observed the synchronous appearance of both these neoplasms in two patients. The first patient, a 60-year-old female, was diagnosed with breast cancer. She underwent quadrantectomy and sentinel axillary lymph node dissection. Pathological diagnosis was invasive breast cancer non special type (NST), G2 pT1 N0, estrogen receptor (ER) 95%, progesterone receptor (PR) 90%, human epidermal growth factor receptor 2 (Her2) negative, Ki67: 30%. Staging work-up (chest X-ray followed by CT scan) discovered a solid mass of 70 mm in the anterior mediastinum, suspect for thymic tumor lesion, that also showed a tracer uptake at FDG scan (SUVmax 10). Patient underwent thymectomy with pathologic diagnosis of thymoma, subtype B2/B3, stage pT1a pN0 (AJCC TNM 8th edition). The second patient, a 62-year-old woman experiencing post-COVID persistent dyspnea, underwent a CT scan and an FDG PET scan. Imaging showed a thoracic lesion suspicious for thymic neoplasm infiltrating the chest wall (tracer uptake SUVmax 6.7) and simultaneously two contrast-enhanced nodules, one in each breast (left breast: 15 mm, SUVmax 2; right breast: 20 mm, SUVmax 2.6). Surgical biopsies were performed in all the 3 lesions. The pathological diagnoses were: (I) non keratinizing squamous cell carcinoma of the thymus; (II) invasive left breast cancer (NST) ER 90 %, PR 30%, Her2 negative, Ki67: 10%; (III) invasive right breast cancer (NST) ER 90%, PR 30%, Her2 positive (3+), Ki67 10%. The presence of synchronous thymic and breast malignancies appears to be very singular and requires personalized treatment strategies. Furthermore, additional studies are needed to understand if TETs and their related immune system dysregulation could increase the risk of secondary tumors, or whether genetic disorders might be responsible for an increased predisposition to develop synchronous malignancies. In both scenarios, future studies should explore the utility of tailoring screening procedures for TET patients.

Mesonephric Like-Carcinoma (MLCA) of the Uterus with a Predominant Spindled Morphology: A Case Report

Abstract Introduction/Objective Mesonephric-like carcinoma of the uterus is an increasingly recognized carcinoma with mesonephric differentiation, but without association with mesonephric remnants. We present a case of a 60-year-old woman presented with postmenopausal bleeding. Methods/Case Report Pelvic MRI showed possibly a cervical lobulated lesion (4.4cm) extending into the endocervical canal. Initial biopsy of this mass showed a spindle cell neoplasm raising possibility of an endometrial stromal sarcoma. On subsequent radical hysterectomy, there was a mass arising in the lower uterine segment (LUS) with circumferential cervical involvement. The tumor was comprised of sheets of epithelioid to spindle cells with scant cytoplasm and indistinct cell borders. Abundant mitotic figures and foci of necrosis were identified. Focal areas showed dense sclerosis with cords of cells, and only rare areas showed tubule formation with scant secretions. By immunohistochemistry (IHC), the tumor cells were positive for keratin AE1/AE3 (strong, diffuse), TTF-1, p63, p16, CD10 (with luminal accentuation); PAX8, desmin and caldesmon showed focal/rare positivity. Other markers were negative, including GATA3 (patchy, weak), ER and PR. Mismatch repair proteins were intact. Next-generation sequencing (NGS) revealed a KRAS mutation. Considering strong expression of epithelial markers, focal tubule formation with positive TTF-1 and negative GATA-3 labeling, and absence of identified mesonephric remnants, the tumor was classified as a high-grade mesonephric-like carcinoma of the uterus (LUS). Pelvic lymph nodes were negative (pT2 N0), and the patient is receiving cisplatin and external beam radiation. Results (if a Case Study enter NA) NA Conclusion MLCA with a prominent spindled/sarcomatoid component can be difficult to diagnose. Ancillary testing including a broad IHC panel with TTF-1, GATA-3 and NGS may be useful to aid in the diagnosis.

Mastectomy alone for pT1-2 pN0-1 breast cancer patients: when postmastectomy radiotherapy is indicated.

To assess outcome of breast cancer (BC) stages pT1-2 N0-1 after mastectomy alone and to identify prognostic factors calling for the need of postmastectomy radiotherapy. Patients who were not eligible for breast conserving surgery (BCS) were operated on with mastectomy between 1998 and 2008. Locoregional (LRR), distant (DM) control and breast cancer specific survival (BCSS) were retrospectively evaluated. Cumulative incidence (CI) of events was estimated according to Kalbfleisch and Prentice while Gray's test tested difference. Kaplan-Meier method for survival and Cox proportional hazards model for univariable and multivariable analysis were used. A matched pair analysis between mastectomy alone and BCS plus whole breast irradiation (WBI), using the propensity score method, was performed. 1281 pT1-2 N0 and 1081 pT1-2 N1 were identified. Median follow-up was 8.2years (9.2years for survival). Overall, LRR rate was low for both N0 and N1 subgroups (10-year CI, 8.8% and 10.9%, respectively). Young age, lymphovascular invasion and Ki-67 ≥ 20% were proved to be statistically significant prognostic factors at multivariable analysis. The combination of ≥ 2 risk factors increased LRR rate to ≥ 15%. Risk factors combination weighed on LRR rate more than nodal status itself. DM rate doubled moving from negative to positive nodal status (10-year CI 10.5% versus 20.3%, respectively). BCSS remained high in both N0 and N1 subgroups (10-year CI 92.4% versus 84.5%, respectively). Remarkably, all the molecular subtypes except Luminal A significantly affected DM and BCSS both in the N0 and N1 subgroups. Nodes number significantly impacted on DM and BCSS but not on locoregional control. In the matched pair analysis, WBI decreased nodal recurrence rate and improved distant control, without affecting survival. Selected patients, namely those with at least two additional risk factors, presented high enough LRR risk to support the use of postmastectomy radiotherapy in both N0 and N1 subgroups. Moreover, the observation that radiotherapy may provide benefits that go beyond local control deserves to be further investigated.

PT3 N0 Laryngeal Squamous Cell Carcinoma: Oncologic Outcomes and Prognostic Factors of Surgically Treated Patients.

Objectives/HypothesisTo assess the disease control, survival rates, and prognostic factors of exclusive surgical treatment for patients with pT3 N0 laryngeal squamous cell carcinoma (LSCC).Study DesignMulticentric retrospective cohort study.MethodsMulticentric retrospective case series of previously untreated patients with pT3 R0N0 LSCC, who received exclusive surgery between 2011 and 2019. Tumor location; subsite involvement; grading; and lymphatic, vascular, and perineural invasion were reported. Overall survival (OS), disease‐specific survival (DSS), and disease‐free survival (DFS) were measured.ResultsFifty‐four patients (mean age 67.1; male sex 83.3%; mean follow‐up period 37 months) underwent total laryngectomy (48.1%) or partial laryngectomy (51.9%). Ipsilateral or bilateral neck dissection was performed in 46 (85.2%) cases. Perineural invasion was more frequent in case of supraglottic involvement than glottic involvement (85.7% vs. 14.3%, P = .03). Five (9.3%) patients experienced recurrence (3 local recurrences, 1 nodal recurrence, 1 distant recurrence). Rate of recurrence differed between glottic (0%), supraglottic (80%), and transglottic (20%) tumors (P = .01), with a lower risk yielded by glottic involvement (odds ratio [OR], 0.05, 95% confidence interval [95% CI], 0.01–0.56, P = .01). A higher risk was recorded in case of perineural invasion (OR, 66.0, 95% CI, 1.41–3085.3, P = .03). The OS, DSS, and DFS were 79.6%, 96.3%, and 90.7%, without differences regarding the type of surgery. The DFS was lower in case of supraglottic involvement when compared to purely glottic LSCC (83.9% vs. 100%, P = 0.02).ConclusionsExclusive surgery is a safe option for patients with pT3 R0N0 LSCC. Adjuvant treatments or closer follow‐up monitoring might be considered in case of supraglottic involvement or perineural invasion.Level of Evidence4 Laryngoscope, 131:2262–2268, 2021

Oncological outcomes of pathologically organ-confined, lymph node-positive prostate cancer after radical prostatectomy

BackgroundThe aim of this study was to investigate the impact of lymph-node involvement on oncological outcomes in patients with pathologically organ-confined prostate cancer (pT2 CaP) after radical prostatectomy (RP). MethodsWe retrospectively analyzed 9,631 pT2 CaP patients who underwent RP at a single institution between 1998 and 2018. Kaplan-Meier plots and Cox regression models (CRMs) assessed biochemical recurrence (BCR)-free survival and metastasis-free survival (MFS) according to N-stage. In subgroup analyses of N1 patients, Kaplan-Meier plots and CRMs were stratified according to adjuvant treatment. ResultsOf 9,631 pT2 staged patients, 241 (2.5%) harbored lymph-node metastases after RP (pN1). The median follow-up was 60.8 months. No pT2 N1-staged patient died due to CaP. The 5-year BCR-free survival rates were 54.7 vs. 88.4% in pT2 N1 vs. pT2 N0 patients, respectively (P < 0.001). The 5-year MFS rates were 92.5 vs. 98.9% in pT2 N1 vs. pT2 N0 patients, respectively (P < 0.001). Within pT2 N1 patients, presence of ≥3 positive lymph nodes was an independent risk factor for BCR (hazard ratio [HR] 3.4, P < 0.001) and for metastatic progression (HR 1.7, P = 0.04). Finally, 3-year BCR-free survival was improved in pT2 N1 patients treated with adjuvant radiation therapy (87.1% vs. 63.7% for patients who received other treatment options [P < 0.001]). ConclusionPatients with pathologically organ-confined but lymph node-positive CaP exhibited favorable oncological outcomes after RP. Presence of ≥3 positive LNs predicted higher rates of BCR and metastatic progression. In consequence, in pT2 N1 patients treated with RP with ≥3 positive LNs, adjuvant treatment may be considered.9

Proton Accelerated Partial Breast Irradiation: Clinical Outcomes at a Planned Interim Analysis of a Prospective Phase 2 Trial

To perform a planned interim analysis of acute (within 12 months) and late (after 12 months) toxicities and cosmetic outcomes after proton accelerated partial breast irradiation (APBI). A total of 100 patients with pTis or pT1-2 N0 (≤3cm) breast cancer status after segmental mastectomy were enrolled in a single-arm phase 2 study from 2010 to 2019. The clinically determined postlumpectomy target volume, including tumor bed surgical clips and operative-cavity soft-tissue changes seen on imaging plus a radial clinical expansion, was irradiated with passively scattered proton APBI (34 Gy in 10 fractions delivered twice daily with a minimum 6-hour interfraction interval). Patients were evaluated at protocol-specific time intervals for recurrence, physician reports of cosmetic outcomes and toxicities, and patient reports of cosmetic outcomes and satisfaction with the treatment or experience. Median follow-up was 24 months (interquartile range [IQR], 12-43 months). Local control and overall survival were 100% at 12 and 24 months. There were no acute or late toxicities of grade 3 or higher; no patients experienced fat necrosis, fibrosis, infection, or breast shrinkage. Excellent or good cosmesis at 12 months was reported by 91% of patients and 94% of physicians; at the most recent follow-up, these were 94% and 87%, respectively. The most commonly reported late cosmetic effect was telangiectasis (17%). The total patient satisfaction rate for treatment and results at 12 and 24 months was 96% and 100%, respectively. Patients' mean time away from work was 5 days (IQR, 2-5 days), and the median out-of-pocket cost was $700 (IQR, $100-$1600). The mean left-sided heart dose was 2 cGy (range, 0.2-75 cGy), and the mean ipsilateral lung dose was 19 cGy (range, 0.2-164 cGy). Proton APBI is a maturing treatment option with high local control, favorable intermediate-term cosmesis, high treatment satisfaction, low treatment burden, and exceptional heart and lung sparing.

PT1 Colorectal Cancer Detected in a Colorectal Cancer Mass Screening Program: Treatment and Factors Associated with Residual and Extraluminal Disease.

Simple SummaryOur study has evaluated the burden of pT1 CRC (confined to submucosa) detected during the first round of a CRC screening program, the surgery related complications and the factors related to four relevant outcomes: initial endoscopic resection, surgery rescue and residual disease after endoscopic resection and, finally, extraluminal disease after surgical resection. 38% of the CRC were detected in this stage.74.9% were initially resected endoscopically and 43.8% did not require surgery. There were inhospital surgical complications in 30.7%, mainly mild with no death and complications after discharge in 16.3% of the patients Residual disease was detected in 12 (4.3%) after endoscopic resection and extraluminal disease in 18 (8.6%) patients after surgery. We have determined several variables independently associated with the four outcome variables evaluated.The aim of this study is to describe the treatment of pT1 colorectal cancer (CRC) in a mass screening program, the surgery-related complications and the factors associated with residual disease after endoscopic resection and extraluminal disease after surgery. We included in this retrospective analysis all the pT1 CRC detected in the Galician CRC screening program between May 2013 and June 2019. We determined which variables were independently associated with the outcomes of the study through a multivariable logistic regression analysis. We included 370–354 pT1 N0(X), 16 pT1N1- out of the 971 CRC detected; 277 (74.9%) were resected endoscopically and 162 (43.8%) were not referred to surgery. There were surgical complications in 30.7% and 16.3% of the patients during hospitalization and after discharge. Residual disease was detected in 12 (4.3%) after endoscopic resection and extraluminal disease in 18 (8.6%) patients after surgery. The variables independently associated with initial endoscopic resection were a pedunculated morphology (OR 33.1, 95% CI 4.3–254), a diameter ≥ 20 mm (OR 3.94, 95% CI 1.39–11.18) and a Site–Morphology–Size–Access score < 9 (OR 428, 95% CI 42–4263). The variables related with surgery rescue were a piecemeal resection (OR 4.48, 95% CI 1.48–13.6), an infiltrated/nonevaluable resection border (OR 7.44, 95% CI 2.12–26.0), a non-well-differentiated histology (OR 4.76, 95% CI 1.07–20.0), vascular infiltration (OR 8.24, 95% CI 2.72–25.0) and a Haggitt 4 infiltration of the submucosa (OR 5.68, 95% CI 2.62–12.3). Residual disease after endoscopic resection was associated with an infiltrated/nonevaluable resection border (OR 34.9, 95% CI 4.08–298), a non-well-differentiated histology (OR 6.67, 95% CI 1.05–50.0), and the vascular infiltration of the submucosa (OR 7.61, 95% CI 1.55–37.4). The variables related with extraluminal disease after surgical resection were no endoscopic resection (OR 4.34, 95% CI 1.26–14.28), a non-well-differentiated histology (OR 4.35, 95% CI 1.39–14.29) and the lymphatic infiltration of the submucosa (OR 4.8, 95% CI 1.32–17.8). In a CRC screening program, although most of pT1 CRC are candidates for endoscopic treatment, surgery is a safe procedure. We have defined some easy to evaluate variables that can be used in the decision-making process.

Prognostic Factor of Completely Resected and Pathologic T3 N0 M0 Thymic Epithelial Tumor

A multiinstitutional study was conducted to analyze prognosticators of completely resected and pathologic T3 N0 M0 (pT3 N0 M0) stage thymic epithelial tumors. A total of 607 patients with surgically treated thymic epithelial tumors between June 1988 and December 2017 were enrolled. A Cox proportional hazards model and an inverse probability of treatment weighting-adjusted analysis using the propensity score were performed. A total of 394 patients with thymoma and 130 patients with thymic carcinoma underwent complete tumor resections. Forty-one thymomas and 49 thymic carcinomas were confirmed as pT3 N0 M0 stage tumors. Postoperative adjuvant radiotherapy was associated with improved disease-free and overall survival in patients with thymoma (hazard ratio [HR], 0.40; 95% confidence interval [CI], 0.23 to 0.69; and HR, 0.24; 95% CI, 0.11 to 0.52, respectively) and in patients with thymic carcinoma (HR, 0.15; 95% CI, 0.07 to 0.33; and HR, 0.12; 95% CI, 0.05 to 0.31, respectively). Although lung invasion was associated with poor disease-free survival (HR, 3.28; 95% CI, 1.90 to 5.89) and overall survival (HR, 2.60; 95% CI, 1.21 to 6.07), male sex (HR, 1.88; 95% CI, 1.10 to 3.18), older age (HR, 2.77; 95% CI, 1.29 to 5.70), and advanced histologic features (HR, 3.84; 95% CI, 1.42 to 14.51) were associated with poor overall survival in patients with pT3 N0 M0 thymoma. Adjuvant chemotherapy was associated with improved disease-free survival (HR, 0.11; 95% CI, 0.03 to 0.41) and overall survival (HR, 0.11; 95% CI, 0.06 to 0.20) in patients with pT3 N0 M0 thymic carcinoma with superior vena cava or innominate vein invasion. Postoperative radiotherapy was associated with improved survival in patients with pT3 N0 M0 thymic epithelial tumors. Lung invasion was associated with poor survival in patients with pT3 N0 M0 thymoma. Adjuvant chemotherapy was associated with improved survival in patients with pT3 N0 M0 thymic carcinoma with superior vena cava or innominate vein invasion.

Should immunohistochemical expression of mismatch repair (MMR) proteins and microsatellite instability (MSI) analysis be routinely performed for poorly differentiated colorectal neuroendocrine carcinomas?

SummaryColorectal poorly differentiated neuroendocrine carcinomas (NECs) are typically associated with poor outcomes. The mechanisms of their aggressiveness are still being investigated. Microsatellite instability (MSI) has recently been found in colorectal NECs showing aberrant methylation of the MLH1 gene and is associated with improved prognosis. We present a 76-year-old lady with an ascending colon tumour showing features of a pT3 N0 R0, large cell NEC (LCNEC) following right hemicolectomy. The adjacent mucosa showed a sessile serrated lesion (SSL) with low-grade dysplasia. Immunohistochemistry showed loss of expression for MLH1 and PMS2 in both the LCNEC and dysplastic SSL. Molecular analysis indicated the sporadic nature of the MLH1 mismatch repair (MMR) protein-deficient status. Our patient did not receive adjuvant therapy and she is alive and disease-free after 34 months follow-up. This finding, similar to early-stage MMR-deficient colorectal adenocarcinoma, is likely practice-changing and will be critical in guiding the appropriate treatment pathway for these patients. We propose that testing of MMR status become routine for early-stage colorectal NECs.Learning points:Colorectal poorly differentiated neuroendocrine carcinomas (NECs) are known to be aggressive and typically associated with poor outcomes.A subset of colorectal NECs can display microsatellite instability (MSI) with mismatch repair (MMR) protein-deficient status.MMR-deficient colorectal NECs have been found to have a better prognosis compared with MMR-proficient NECs.MMR status can be detected using immunohistochemistry.Immunohistochemistry for MMR status is routinely performed for colorectal adenocarcinomas.Immunohistochemical expression of MMR protein and MSI analysis should be performed routinely for early-stage colorectal NECs in order to identify a subgroup of MMR-deficient NECs which are associated with a significantly more favourable prognosis.