Clinical Stage IVA Research Articles

Protocol summary of a randomized phase III study: comparing systemic therapy with and without debulking surgery (primary tumour resection) for clinical stage IVA (cT1-2bN0-1M1a) non-small cell lung cancer with radiologically undetermined pleural dissemination JCOG2103 (DEBULK-LUNG).

In patients with non-small cell lung cancer (NSCLC) who present with radiologically undetermined malignant pleural dissemination or incidental surgical diagnosis of the same, surgery is generally not the preferred option; systemic therapy is favoured. However, there is no consensus on incorporating primary site resection into the treatment plan. Retrospective analyses hint at potential benefits of combining systemic therapy with primary site resection, but prospective studies have yet to confirm these findings. Consequently, we have planned a multicentre, open-label, randomized controlled phase III trial to assess the efficacy of adding primary site resection to standard systemic therapy for stage IVA (cT1-2bN0-1M1a) NSCLC patients with radiologically undetermined pleural dissemination. The primary endpoint is overall survival. We aim to enroll 170 patients from 71 institutions over 5 years. This trial is registered at the Japan Registry of Clinical Trials (jRCT) under study number jRCTs031220666.

Rare recurrence pattern after complete response to chemotherapy in a patient with rectal cancer: a case report

BackgroundColorectal cancer (CRC) often metastasizes to the liver, lungs, lymph nodes, and peritoneum but rarely to the bladder, small intestine, and skin. We here report the rare metastasis of anal cancer in the left bladder wall, followed by metastases to the small intestine and skin, after abdominoperineal resection and left lateral lymph node dissection with chemotherapy in a patient with clinician Stage IVa disease.Case presentationA 66-year-old man presented with 1-month history of bloody stool and anal pain and diagnosed with clinical Stage IVa anal cancer with lymph node and liver metastases (cT3, N3 [#263L], M1a [H1]). Systemic chemotherapy led to clinical complete response (CR) for the liver metastasis and clinical near-CR for the primary tumor. Robot-assisted laparoscopic perineal rectal resection and left-sided lymph node dissection were performed. Computed tomography during 18-month postoperative follow-up identified a mass in the left bladder wall, which was biopsied with transurethral resection, was confirmed as recurrent anal cancer by histopathologic evaluation. After two cycles of systemic chemotherapy, partial resection of the small intestine was performed due to bowel obstruction not responding to conservative therapy. The histopathologic evaluation revealed lymphogenous invasion of the muscularis mucosa and subserosa of all sections. Ten months after the first surgery for bowel obstruction and two months before another surgery for obstruction of the small intestine, skin nodules extending from the lower abdomen to the thighs were observed. The histopathologic evaluation of the skin biopsy specimen collected at the time of surgery for small bowel obstructions led to the diagnosis of skin metastasis of anal cancer. Although panitumumab was administered after surgery, the patient died seven months after the diagnosis of skin metastasis.ConclusionsThis case illustrates the rare presentation of clinical Stage IVa anal cancer metastasizing to the bladder wall, small intestine, and skin several years after CR to chemotherapy.

Resection of the Primary Tumor and Survival in Patients with Single-Site Synchronous Oligometastatic Non-Small Cell Lung Cancer: Propensity-Matched Analysis of the National Cancer Database.

Local therapy for the primary tumor is postulated to remove resistant cancer cells as well as immunosuppressive cells from the tumor microenvironment, potentially improving response to systemic therapy (ST). We sought to determine whether resection of the primary tumor was associated with overall survival (OS) in a multicentric cohort of patients with single-site synchronous oligometastatic non-small cell lung cancer. Using the National Cancer Database (2018 to 2020), we evaluated patients with clinical stage IVA disease who received ST and stratified the cohort based on receipt of surgery for the primary tumor (S). We used multivariable and propensity score-matched analysis to study factors associated with S (logistic regression) and OS (Cox regression and Kaplan-Meier), respectively. Among 12,215 patients identified, 2.9% (N = 349) underwent S and 97.1% (N = 11,886) ST (chemotherapy or immunotherapy) without surgery. Patients who underwent S were younger, more often White, had higher income levels, were more likely to have private insurance, and were more often treated at an academic facility. Among those who received S, 22.9% (N = 80) also underwent resection of the distant metastatic site. On multivariable analysis, metastasis to bone, N+ disease, and higher T-stages were independently associated with less S. On Cox regression, S and resection of the metastatic site were associated with improved survival (hazard ratio 0.67, 95% CI 0.56 to 0.80 and hazard ratio 0.80, 95% CI 0.72 to 0.88, respectively). After propensity matching, OS was improved in patients undergoing S (median 36.8 vs 20.8 months, log-rank p < 0.001). Advances in ST for non-small cell lung cancer may change the paradigm of eligibility for surgery. This study demonstrates that surgical resection of the primary tumor is associated with improved OS in selected patients with single-site oligometastatic disease.

The Relationship Between Poly-ADP-Ribose Polymerase-1 (PARP-1) Expression with Clinicopathological Characteristics of Nasopharyngeal Carcinoma in Bali, Indonesia

Background: According to epidemiological research conducted in Bali, nasopharyngeal carcinoma (NPC) is the most common cancer among males, accounting for 4.9% of total cases reported between 2017 and 2019. NPC is typically detected at stage IV, indicating the presence of distant metastasis by malignant cells. However, research on the role of Poly-ADP-Ribose Polymerase-1 (PARP-1) in this type of cancer is still limited. Therefore, this research aims to investigate the relationship between PARP-1 and the clinicopathological aspects of NPC.Methods: This research employed an analytical observational design with a cross-sectional approach. From January 2018 to July 2022, biopsy tissue samples were collected from NPC patients, strictly following predefined inclusion and exclusion criteria. The clinical data of these patients were extracted from electronic medical records. Subsequently, the collected samples were subjected to immunohistochemical staining for PARP-1. The interpretation of PARP-1 results was conducted using the H-Score method. Data were analyzed using statistical software, specifically SPSS version 25.Results: The results showed that high PARP-1 expression was detected in 18 samples (62.1%), while the low aspect was observed in 11 samples (37.9%). Independent T-test analysis was conducted for sex, age, and clinical stage. No significant difference was found in the mean PARP-1 H-score among groups based on gender, age, and lymph node enlargement, with p-values of 0.68, 0.71, and 0.74, respectively. However, a statistically significant association was found between PARP-1 expression and clinical stage (p=0.02, 95% CI 1.45 – 63.50). Multivariate analysis showed that sex, age, lymph node enlargement, and clinical stage accounted for 22.1% of the variation in PARP-1 expression, with the clinical stage demonstrating a significant correlation (p=0.02). Conclusions: The clinicopathological data of NPC indicate a male-to-female ratio of 3:1. It was discovered that clinical stages IVA and IVB were the most commonly observed stages. Statistically significant differences were found in the mean and proportion of PARP-1 H-scores across different clinical stages. Future reviews need to include other histological subtypes and employ a prospective research design to evaluate the relationship between PARP-1 and NPC.

Robot-assisted thoracic surgery for stages IIB–IVA non-small cell lung cancer: retrospective study of feasibility and outcome

Robot-assisted thoracic surgery (RATS) for higher stages non-small cell lung carcinoma (NSCLC) remains controversial. This study reports the feasibility of RATS in patients with stages IIB–IVA NSCLC. A single-institute, retrospective study was conducted with patients undergoing RATS for stages IIB–IVA NSCLC, from January 2015 until January 2020. Unforeseen N2 disease was excluded. Data were collected from the Dutch Lung Cancer Audit database. Conversion rate, radical (R0) resection rate, local recurrence rate and complications were analyzed, as were risk factors for conversion. RATS was performed in 95 patients with NSCLC clinical or pathological stages IIB (N = 51), IIIA (N = 39), IIIB (N = 2) and IVA (N = 3). 10.5% had received neoadjuvant chemoradiotherapy. Pathological staging was T3 in 33.7% and T4 in 34.7%. RATS was completed in 77.9% with a radical resection rate of 94.8%. Lobectomy was performed in 67.4% of the total resections. Conversion was for strategic (18.9%) and emergency (3.2%) reasons. Pneumonectomy (p = 0.001), squamous cell carcinoma (p < 0.001), additional resection of adjacent structures (p = 0.025) and neoadjuvant chemoradiation (p = 0.017) were independent risk factors for conversion. Major post-operative complications occurred in ten patients (10.5%) including an in-hospital mortality of 2.1% (n = 2). Median recurrence-free survival was estimated at 39.4 months (CI 16.4–62.5). Two- and 5-year recurrence-free survival rates were 53.8% and 36.7%, respectively. This study concludes that RATS is safe and feasible in higher staged NSCLC tumors after exclusion of unforeseen N2 disease. It brings new perspective on the potential of RATS in higher stages, dealing with larger and more invasive tumors.

Salvage Surgery for Advanced Lung Adenocarcinoma After Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Treatment

BackgroundNo published studies to date have evaluated the detailed pathologic and genetic features of lung adenocarcinoma after epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy and salvage surgery. We aimed to evaluate the pathologic and genetic changes of tumors in patients with advanced lung adenocarcinoma treated with EGFR TKI therapy and salvage surgery. MethodsThis study retrospectively collected data from 29 advanced lung adenocarcinoma patients who underwent EGFR TKI therapy, followed by salvage operation, between January 2010 and December 2018. All patients had partial response or stable disease without evidence of progressive disease. Next-generation sequencing was used to determine whether acquired resistant mutations in morphologically treatment-sensitive and morphologically treatment-resistant regions of tumor existed. ResultsThere were 3, 22, and 4 patients with clinical stage IIIB, IVA, and IVB, respectively. After a mean TKI treatment duration of 134 days, 27 patients had partial response, 2 had stable disease, and 27.6% of patients were downstaged before salvage surgery. All patients had residual viable tumor cells in their tumor bed; 5 patients (17.2%) had a major pathologic response. Acquired T790M mutations (n = 4), histologic transformations (n = 2), and acquired T790M mutation with histologic transformation (n = 1) were identified in the morphologically treatment-resistant regions of tumors. The 3-year overall survival was 75.9%. ConclusionsThe presence of morphologically treatment-resistant tumor regions with acquired T790M mutations and histologic transformations demonstrate the existence of resistant subclones in TKI-treated tumors before disease progression. Salvage surgery performed in selected patients before disease progression may improve survival by removing TKI-resistant subclones.

Evaluation of anaplastic thyroid carcinoma in the Kurdistan region of Iraq

BackgroundAnaplastic thyroid carcinoma is a rare and lethal disease that accounts for 1–2% of thyroid malignancies. It is an aggressive locoregional disease with a high rate of distant metastasis, a poor prognosis, and a mean survival rate of 3–6 months after diagnosis. This retrospective study aimed to analyse the clinical and pathological features of ATC to assess treatment procedures and its outcome.MethodsWe analysed data from 22 patients diagnosed with ATC from 2018 to 2021, using the Kaplan-Meier method and log-rank test to determine overall survival.ResultsPatients’ median age was 64.3 ± 17.1 years. Females were more affected (male/female ratio: 1:1.7); 14 cases occurred in females (63.6.4%), and eight in males (36.4%). The most common manifestations were neck enlargement (81.8%) and dyspnoea (72.27%), and the tumour size was > 4 cm in 17 (77.3%) patients. The percentage of cases that presented in clinical-stage IVA was 36.4%, with 31.8% presenting in clinical-stage IVB and 31.8% presenting in clinical-stage VIB. Among 22 cases, 14 (63.6%) were operable, and 8 (36.4) were inoperable (p = 0.015). Multimodal therapies were associated with better survival (surgery plus radiotherapy without systemic treatment, P = 0.063). The median overall survival was three months (IC 95%, 0.078–5.922). One-year and two-year survival rates were 9% and 4.5%, respectively.ConclusionATC is a rapidly growing cancer that, fortunately, is rare. Early diagnosis and multimodality treatment may provide a better quality of life and survival time for this group of patients.

33615 Nasosinusal mucosal melanoma

A 73-year-old male, former tobacco smoker, with a personal history of cardiac arrhythmias and hypertension and a first-degree relative with colorectal cancer, consulted for 2 months of epistaxis associated with left nasal obstruction, proptosis, epiphora and ipsilateral diplopia. Previous rhinoscopy showed a polypoid tumor, occupying the left nostril and extending to the pyriform aperture, blackish and with a visible vascular pattern that displaced the septum towards the right nostril. A simple CT scan of the craniofacial mass showed lytic tumor lesions in the left nostril with extension into the maxillary sinus, involving turbinates, nasal septum, ethmoidal cells, orbital lamina and left frontal sinus. The diagnosis was complemented with histopathology, revealing nasal mucosal melanoma, ulcerated, without presence of mitosis, lymphovascular or neural invasion. MRI and PET did not show distant metastasis. The patient required multidisciplinary management and was staged as T4aN0M0, clinical stage IVa (according to AJCC TNM classification) and stage I (according to Ballantyne classification). Surgery was ruled out, indicating management with radiotherapy and pembrolizumab 200 mg every 21 days in the current follow-up, with partial improvement of nasal obstruction, without evidence of clinical progression. The interest of this case lies in the infrequent and aggressive presentation of melanoma of the nasal mucosa, being an oncologic entity of low prevalence that corresponds to 1% of the total melanomas and less than 5% of the neoplasias of the nasosinusal tract, having worse prognosis than cutaneous melanoma due to its recurrence and high metastatic potential.

A phase II study of osimertinib in combination with platinum plus pemetrexed in patients with EGFR-mutated, advanced non–small cell lung cancer: The OPAL study (NEJ032C/LOGIK1801).

9097 Background: Osimertinib (OSI), a third-generation EGFR-tyrosine kinase inhibitor (EGFR-TKI), is now a standard treatment for previously untreated EGFR-mutated (EGFRm) advanced non-small cell lung cancer (NSCLC). In the two randomized phase 3 studies, progression-free survival (PFS) and overall survival were statistically significant and clinically longer with gefitinib and platinum-based chemotherapy compared with gefitinib monotherapy. Based on these data, we have planned this phase 2 study to evaluate the safety and efficacy of OSI combined with platinum-based chemotherapy. Patients and Methods: This multicenter phase 2 study enrolled patients (pts) with clinical stage IIIB, IIIC, IVA, IVB or postoperative recurrent, previously untreated EGFRm NSCLC. Pts received oral OSI 80mg once daily (QD), with either cisplatin 75mg/m2 (arm A) or carboplatin [area under the curve (AUC) = 5, arm B], plus pemetrexed (PEM) 500 mg/ m2 every 3 weeks (Q3W) for four cycles. In both arms, maintenance was OSI 80mg QD with PEM 500 mg/ m2 Q3W until disease progression or discontinuation. The co-primary endpoints were the safety and the objective response rate (ORR), and the secondary endpoints included the complete response rate (CRR), disease control rate (DCR), and PFS. Results: From July 2019 to February 2020, 67 pts (34 pts in Arm A; 33 pts in arm B) were enrolled: median (range) age 67 (26-75) years; 43 (64.2%) female; 46 (68.7%) ECOG PS 0; 66 (98.5%) adenocarcinoma; 31 (46.3%) EGFR exon19 deletion, 35 (52.2) L858R, and 1 (1.5%) both. One pt did not comply with the eligibility criteria and was excluded from the efficacy analysis. At data cut off (August 31, 2021), 27 (40.3%) pts [15 (44.1%) in arm A and 12 (36.4%) in arm B] had discontinued the protocol treatment, including 9 (13.4%) pts [5 (14.7%) in arm A and 4 (12.1%) in arm B] due to the adverse event (AE). The rate of grade (G) ≥ 3 AEs were 91.0% (88.2% in arm A and 93.9% in arm B). For the safety, neutropenia, anemia and thromobocytopenia were numerically higher in arm B and the rates of G ≥ 3 were 29.4%/60.6%, 14.7%/27.3% and 0.0%/42.4% in arm A/B, respectively. G ≥ 3 QTc interval prolonged and G ≥ 2 anorexia were observed in 14.7%/21.2% and 26.5%/24.2%, respectively. For the efficacy, the ORR was 90.9% [95% confidence interval (CI); 84.0-97.8%]. The CRR/DCR were 3.0%/97.0% (95% CI; 0.0-7.2%/92.8%-100.0%), respectively. At a median follow-up time of 21.4 months (range, 18.2-25.7), median PFS was not reached in both A and B, with an estimated 12-/24-months PFS rate of 90.4%/70.0%. Conclusions: OSI combined with platinum-based chemotherapy for previously untreated EGFRm advanced NSCLC showed the excellent efficacy with tolerable toxicity. This combination treatment is highly promising and should be validated in the phase 3 study. Clinical trial information: jRCTs031180226.

Detecting Interval Distant Metastases With 18F-FDG PET/CT After Neoadjuvant Chemoradiotherapy for Locally Advanced Esophageal Cancer.

PurposePatients with esophageal cancer can develop distant metastases between the start of neoadjuvant chemoradiotherapy (nCRT) and planned surgery (ie, interval distant metastases). 18F-FDG PET/CT restaging after nCRT detects interval distant metastases in ~8% of patients. This study aimed to identify patients for whom 18F-FDG PET/CT restaging after nCRT could be omitted using an existing prediction model predicting for interval distant metastases or by using clinical stage groups.Patients and MethodsPatients with locally advanced esophageal cancer who underwent baseline and restaging 18F-FDG PET/CT, nCRT, and were planned for esophagectomy between 2017 and 2021 were eligible for inclusion in this retrospective study. The primary outcome was the existing model’s external performance (ie, discrimination and calibration) for predicting interval distant metastases. The existing model predictors included tumor length, cN status, squamous cell carcinoma histology, and baseline SUVmax. The secondary outcome determined the clinical stage groups (AJCC/UICC eighth edition) for adenocarcinoma and squamous cell carcinoma for which the incidence of interval distant metastases was <10%.ResultsIn total, 127 patients were included, of whom 17 patients developed interval distant metastases (13%; 95% confidence interval [CI], 8%–21%) and 9 patients were deemed to have false-positive lesions on 18F-FDG PET/CT (7%; 95% CI, 2%–11%). Applying the existing model to this cohort yielded a discriminatory c-statistic of 0.56 (95% CI, 0.40–0.72). The calibration of the existing model was poor (ie, mostly underestimating the actual risk). The incidence of true-positive versus false-positive interval distant metastases for patients with clinical stage II disease was 5% versus 0%; clinical stage III, 14% versus 8%; and clinical stage IVa, 22% versus 9%.ConclusionsThe existing prediction model cannot reliably identify patients at risk for developing interval distant metastases after nCRT for esophageal cancer. Omission of 18F-FDG PET/CT restaging after nCRT could be considered in patients with clinical stage II esophageal cancer.

Cisplatin and Irinotecan as First-Line Chemotherapy for Previously Untreated Metastatic Thymic Carcinoma: Updated Analysis.

Platinum-based chemotherapy is the de facto standard treatment for metastatic or unresectable thymic carcinoma. The optimal chemotherapy regimen has not yet been determined, including whether this should be combined with a second- or third-generation anti-cancer agent. We retrospectively evaluated the data of patients with metastatic or unresectable thymic carcinoma who were treated with a combination of cisplatin and irinotecan as first-line chemotherapy between 2002 and 2021 (trial registration UMIN000012175). The primary endpoint was response rate according to the RECIST criteria version 1.1. Secondary endpoints were disease control rate, progression-free survival (PFS), overall survival (OS), and toxicity (adverse events). Some patients analyzed in this study were also included in the previous trial, which was terminated early. For this analysis, we included 18 patients with a median age of 56 years and an Eastern Cooperative Oncology Group performance status of 0 or 1. All patients had clinical stage IVa or IVb thymic carcinoma according to the Masaoka-Koga staging system. The response rate was 44% and the disease control rate was 89%. The median PFS was 8.4 months (95% confidence interval (CI): 2.7–11.6 months) and the median OS was 45.6 months (95% CI: 15.7–69.1 months). Grade 3 or worse hematological toxicity was observed in 5 patients and grade 3 or worse non-hematological toxicity was observed in 3 patients. None of the patients developed febrile neutropenia, and no treatment-related deaths occurred. Thus, the combination of cisplatin and irinotecan as first-line chemotherapy for metastatic thymic carcinoma showed efficacy and acceptable toxicity.

Short and Long-term Outcomes Among High-Volume vs Low-Volume Esophagectomy Surgeons at a High-Volume Center

To determine associations between surgeon volume and esophagectomy outcomes at a high-volume institution. All esophagectomies for esophageal cancer at our institution from August 2005 to August 2019 were reviewed. Cases were divided by surgeon into low, <7 cases/year, vs high volume, ≥7 cases/year, based on Leapfrog Group recommendations. Surgeons remained 'high-volume' after one year of ≥7 cases. Demographics, comorbidities, course of care, and long-term outcomes were compared. In total, 1029 cases were evaluated; 120 performed by low-volume surgeons vs 909 by high-volume surgeons. Never-smokers, atrial fibrillation, and clinical Stage IVa patients were associated with high-volume surgeons. Other demographics were similar. Low-volume surgeons did more open cases, 45.8% vs 14.5%, P < 0.01. Low-volume surgeons had more complications than high-volume surgeons (71.7% vs 57.6%, P < 0.01), specifically Grade II and III (59.2% vs 46.8%, P=0.01, and 44.2% vs 27.0%, P <0.01). No differences were seen in anastomotic leak rate, 90-day mortality, recurrences, 5-year overall survival (46.7% low-volume vs 49.3% high-volume, P=0.64), or 5-year disease-free survival (35.7% low-volume vs 42.2% high-volume, P=0.27). In multivariable logistic regression for Grade III or higher complications, high-volume surgeons had an odds ratio of 0.56 (95% confidence interval 0.36-0.87) for complications. Our study found higher rates of open esophagectomies and complications in low-volume esophagectomy surgeons compared to high-volume surgeons at the same, high-volume institution. However, low-volume surgeons were not associated with worse survival outcomes compared to high-volume surgeons. Low-volume esophagectomy surgeons may benefit from mentoring and support to improve perioperative outcomes; these efforts are underway at our institution.

Efficacy of Gefitinib and Methorexate in Patients With Advanced Stage and Recurrent Head and Neck Cancer.

Introduction: Gefitinib, a tyrosine kinase inhibitor (TKI), is an epidermal growth factor receptor (EGFR)-blocking drug that is effective in the treatment of lung cancer with EGFR mutations; however, its benefits for head and neck cancers are uncertain. Therefore, this study aims to determine the efficacy of gefitinib and methotrexate in patients with advanced-stage or recurrent head and neck cancer.Methodology: Two hundred patients of age >18 years with advanced clinical stage either IVA or IVB and recurrent cases were included in this study. Patients were randomly allocated to the gefitinib (n=100) or methotrexate (n=100) group. Each patient was evaluated for demographic variables, addictions, comorbidities and history of cancer followed by clinical and radiological evaluation. Treatment response was evaluated with standard Response Evaluation Criteria in Solid Tumors (RECIST). The primary end point of the study was overall response rate (ORR). SPSS version 25 (IBM Corp., Armonk, NY, USA) was used to analyze data.Results: Overall response of therapy was partial 11% vs 8%, stable disease 52% vs 40%, and progressive disease 33% vs 40% in gefitinib and methotrexate groups respectively. Three patients were lost to follow up in the gefitinib group and one patient in the methotrexate group. Only one death was reported in the gefitinib group and four in the methotrexate group. In recurrent cases, six patients treated with gefitinib showed partial response whereas no case of partial response was reported in the methotrexate group (27.3% vs 0%). Similarly, in the methotrexate group significantly higher numbers of progressive and stable diseases were reported for recurrent cases than in the gefitinib group (p=0.045).Discussion: Gefitinib had marginally better results in terms of overall response and safety as compared to methotrexate, specifically in recurrent cases of head and neck cancer. This benefit for recurrent cases and ease of administration, leading to fewer hospital visits in the coronavirus disease 2019 (COVID-19) era, makes gefitinib superior to methotrexate.

Association of Primary Treatment Modality for Advanced-Stage Oropharyngeal Squamous Cell Carcinoma With Survival Outcomes

Definitive chemoradiotherapy and upfront surgical treatment are both accepted as the standard of care for advanced-stage oropharyngeal squamous cell carcinoma. However, the optimal primary treatment modality remains unclear. To evaluate the comparative effectiveness of definitive chemoradiotherapy and upfront surgical treatment for advanced-stage oropharyngeal cancer. This retrospective comparative effectiveness analysis used data from the population-based Taiwan Cancer Registry. Included patients were diagnosed with clinical stage III or IV oropharyngeal squamous cell carcinoma from 2007 to 2015 and were identified from the registry. Patients with T4b or N3 disease were excluded. Data were analyzed from June 2019 through December 2020. Definitive chemoradiotherapy or upfront surgical treatment. The primary outcome was overall survival, for which data were available through December 31, 2018. Secondary outcomes were progression-free survival, locoregional recurrence-free survival, and distant metastasis-free survival. Among 1180 patients, 694 patients (58.8%) were in the definitive chemoradiotherapy group and 486 patients (41.2%) were in the upfront surgical treatment group. The median (interquartile range) follow-up was 3.62 (1.63-5.47) years, and most patients were men (1052 [89.1%] men) with a primary tumor in the tonsils (712 patients [60.3%]), moderately differentiated histology (604 patients [51.2%]), clinical N2 disease (858 patients [72.7%]), and clinical stage IVA disease (938 patients [79.5%]). The mean (SD) age was 54.59 (10.35) years. Primary treatment with an upfront surgical procedure was associated with a decreased risk of death during the study period (hazard ratio [HR], 0.81; 95% CI, 0.69-0.97; P = .02). However, when adjusted for age, subsite, histological grade, and T and N classification, upfront surgical treatment was no longer associated with an increased risk of death during the study period (HR, 0.96; 95% CI, 0.80-1.16; P = .70). Progression-free survival was worse in the group receiving upfront surgical treatment than in the group receiving chemoradiotherapy (HR, 1.64; 95% CI, 1.09-2.46; P = .02), and this difference persisted after adjusting for other factors associated with prognosis (ie, age, tumor subsite, histological grade, and T and N classification) (HR, 1.72; 95% CI, 1.12-2.66; P = .01). This study found that definitive chemoradiotherapy was associated with effectiveness that was comparable with that of upfront surgical treatment when adjusted for baseline factors associated with prognosis. These findings suggest that definitive chemoradiotherapy should be considered to avoid accumulating toxic effects associated with surgical treatment and chemoradiotherapy.

Effect of neoadjuvant systemic therapy given during window trials on quality metrics in resectable head and neck squamous cell carcinoma.

6033 Background: Quality oncologic care, including negative surgical margin status, adequate lymph node yield and prompt initiation of adjuvant treatment, impacts disease control and overall survival in patients with mucosal head and neck squamous cell carcinoma (HNSCC). The aim of this study was to ascertain the effect of neoadjuvant systemic therapy given during window trials on oncologic quality metrics in patients with delayed definitive surgery for a HNSCC. Methods: Treatment-naïve patients with HNSCC participating in one of two window of opportunity clinical trials at UPMC from 2009-2019 were included. Neoadjuvant regimens consisted of one dose of cetuximab (n = 33) or anti-ErbB3 antibody (n = 9) within 28 days of surgery. Sociodemographic, clinical and tumor staging were recorded. The primary outcome was overall oncologic quality, as defined as a composite measure of negative margin status, adequate lymph node yield, completion of adjuvant therapy (if indicated) and time to initiation of adjuvant therapy within 6 weeks of surgery. Secondary outcomes were difference in clinical and pathologic stages and overall survival (OS). Results: A total of 42 patients with a mean age of 57.1 (±10.2) years and median follow-up of 58 months were analyzed. 29 patients had clinical stage IVA disease with 43% (18/42) oral cavity, 36% (15/42) larynx/hypopharynx and 21% (9/42) oropharynx primaries. All patients underwent surgery following neoadjuvant systemic therapy. In 30 patients (71%), all oncologic quality markers were achieved. Pathological downstaging occurred in 21% (9/42) of patients with 4 patients no longer meeting criteria for adjuvant treatment and were observed. 3 patients showed pathological upstaging. The 3-year OS were 76% (95% CI of 63.6-88.4), respectively. Patients with a pathologic downstage migration (64.9%, 95% CI of 49.9-79.8) had higher 5-year OS compared to those without (57.8%, 95% CI of 40.1-76.4, P = 0.046). Conclusions: Most patients receiving neoadjuvant systemic therapy on window trials prior to surgery met all oncologic quality markers. Importantly, even with brief window trial therapy pathologic downstaging was achieved and associated with significantly better overall survival.

Long-term results of definitive chemoradiotherapy for unresectable locally advanced esophageal squamous cell carcinoma.

PurposeThe present study aimed to evaluate the long-term results of definitive chemoradiotherapy (CRT) for unresectable locally advanced esophageal squamous cell carcinoma (LA-ESCC).Materials and methodsWe analyzed eighty patients with unresectable LA-ESCC, who underwent definitive CRT between 2001 and 2014. The 5-year overall survival (OS), cause-specific survival (CSS), and progression-free survival (PFS) rates were calculated, and we investigated the prognostic factors and adverse events.ResultsThe median age was 66 years (range, 41–83 years). Histologically, all patients had squamous cell carcinoma. The most common tumor site was the middle thoracic esophagus in 43 (54%) patients. According to the eighth edition of the Union for International Cancer Control TNM classification, sixty-six patients (83%) had T4 disease, 59 (74%) had regional lymph node (LN) metastases, and 35 (44%) had distant LN metastases beyond the regional LN (M1 LYM) disease. Forty-five (56%) and 35 (44%) patients belong to clinical stages IVA and IVB, respectively. The median follow-up period for survivors was 86 months. The 5-year OS, CSS, and PFS rates were 20.2%, 25.7%, and 18.4%, respectively. On univariate analysis, only the performance status score was significantly associated with better overall survival (p = 0.026). Grade 3 or higher late adverse events were observed in 12 (15%) patients, and these included cardiopulmonary adverse events in 6 (8%) patients. Treatment-related death occurred in 3 (4%) patients.ConclusionWe showed the long-term results of definitive CRT for unresectable LA-ESCC. The survivals are still poor and new treatment strategies need to be developed.

Impact of the Cholangiocarcinoma Component of Combined Hepatocellular/Hepatocholangiocarcinoma on Patient Survival

Abstract Introduction/Objective The radiopathologic correlation, overall prognosis, and best management of combined hepatocellular carcinoma/cholangiocarcinoma (HCC/CC) remains uncharted territory. Methods We studied whether the percentage (%) of the cholangiocarcinoma (CC) component of HCC/CC impacted patient survival. A retrospective analysis was performed including all cases (18) of HCC/CC in the pathology archives from 2011–2019. Tumor beds were submitted entirely in all but 2 specimens, which were representatively sampled. Slides from these cases were reviewed to assess % of CC. Survival was calculated from the date of diagnosis to the date of demise and censored as the date last known alive at the time of the study. Results 13 cases were liver explants, 2 were resections, and 3 were biopsies. 13 cases were from clinical stage II patients, 2 were clinical stage IVA, and 2 were clinical stage IVB. All but one patient in the study group were males. There was no predilection for any specific tumor site. The cases were divided into three groups related to CC percentage: 0–20 (n=5), 21–40 (n=6), and &amp;gt;40% (n=7). AFP was variably elevated in select cases, with the highest values found in the medium and high % groups. Though there was no significant difference in overall survival among the three groups, mean and median survival trended in a downward fashion with increased % CC. Interestingly, radiology read 12 cases as HCC, 1 as intrahepatic CC, and only 1 as cholangiocarcinoma/hepatoma, atypical for HCC. Conclusion We conclude that there is a trend for decreased survival as % CC increases in combined HCC/CC patients, with patients with &amp;gt;20% CC tending to have lower survival rates. Furthermore, incongruity exists between radiologic and pathologic diagnoses of combined HCC/CC. Additional study with a larger sample size will yield more information to understand better prognosis as well as guide more accurate diagnosis of these patients.

525P - Retrospective analysis of outcomes of cisplatin and irinotecan combination chemotherapy for unresectable thymic carcinoma

BackgroundThymic carcinoma is a rare, malignant mediastinal tumor originating from thymic epithelial cells. It exhibits a tendency for metastasis and invasive growth. Unresectable thymic carcinoma is treated with systemic chemotherapy. However, a definitive chemotherapeutic regimen for this entity is yet to be established. The objective of this study was to evaluate the efficacy and safety of cisplatin and irinotecan combination as the first-line chemotherapy. MethodsData pertaining to patients with advanced thymic carcinoma who received cisplatin and irinotecan combination chemotherapy between January 1, 2002 and December 31, 2018, were retrospectively analyzed. The end points were disease control rate, progression free survival, and overall survival. The incidence of significant hematological and non-hematological toxicity was also assessed. ResultsWe identified 17 patients with a median age of 56 years (ECOG performance status: 0 or 1). All patients had clinical stage (Masaoka-Koga staging system) IVa or IVb. Disease control was achieved in 15 patients (88.2%). Median progression-free survival was 7.3 months [95% confidence interval (CI) 2.7–11.6]; median overall survival was 45.6 months (95% CI 9.49–69.5). The outcomes were similar to those achieved with previously reported chemotherapy regimen, CBDCA plus paclitaxel or Cisplatin combination chemotherapy. No treatment-related deaths occurred in this cohort. Grade 3 or worse hematological toxicity was observed in five patients (neutropenia: three patients; anemia: two patients); grade 3 or worse non-hematological toxicity was observed in three patients. None of the patients developed febrile neutropenia. ConclusionsCisplatin and Irinotecan combination chemotherapy may be a safe and effective first-line chemotherapy regimen for unresectable thymic carcinoma. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureY. Hosomi: Honoraria (self): AstraZeneca. All other authors have declared no conflicts of interest.

GR01.05 Site of Oligometastases

GR01.05 Site of Oligometastases

Lymph Node Metastases Diagnosed by 18F-FDG-PET/CT in Esophageal Squamous Cell Cancer Treated With Concurrent Chemoradiotherapy.

To evaluate whether factors related to the clinical staging of lymph node (LN) metastasis diagnosed by 18F-fluorodeoxyglucose positron-emission tomography/computed tomography (PET/CT) correspond to poor survival in esophageal squamous cell cancer (ESCC) patients treated with concurrent chemoradiotherapy (CCRT). A total of 69 patients with curative intent and no prior treatment for ESCC or simultaneous treatment for synchronous cancers were investigated. A maximum standardized uptake value (SUVmax) on the highest image pixel in the LN ≥2.5 was considered positive. Location of the involved LN and its impact on survival were analyzed. In the univariate analysis of location, metastasis of the abdominal site, regional abdominal LN, and left gastric LN station negatively affected overall survival (OS) and disease-free survival (DFS). Other adverse clinical factors influencing OS included T4, clinical stage IVA and body mass index <21.2. In terms of DFS, a further unfavorable factor was primary tumor SUVmax ≥10.4. Abdominal site LN metastasis affected both OS and DFS in multivariate analysis. LN metastasis diagnosed by PET/CT in abdominal sites was an independent predictor affecting both OS and DFS in ESCC patients who underwent curative CCRT.