Advanced Local Disease Research Articles

503 QUALITY OF LIFE AS A PREDICTOR OF POST-ESOPHAGECTOMY SHORT TERM OUTCOMES AND SURVIVAL

Abstract Most esophageal cancer patients present with symptoms that impact quality of life (QOL). In this study, we sought to determine the influence of QOL at diagnosis on postoperative outcomes and survival (OS). Methods A prospectively-collected esophagectomy database (2006–17) was queried to identify patients who completed Functional Assessment of Cancer Therapy-Esophageal module (FACT-E). Demographics/tumor/treatment details, operative variables, complications and OS were collected. Statistical analysis was done using Cox regression, logistic regression, ANOVA or Chi-square tests. Results Of 647 patients underwent esophagectomy in the study period, 359 how completed FACT-E at diagnosis were included in the study (age 64 ± 11, male 82%, stage I:9%, II:15%, III:69%, IV:7%, adenocarcinoma: 78%, neoadjuvant therapy: 70%). Clinical stage I was associated with better QOL at diagnosis (131 ± 2 vs 118 ± 28, p < 0.02). FACT-E > 125 was associated with lower peri-operative mortality (9% vs 1%, 0R = 6.1, P = 0.01), and when divided into quintiles, correlated directly with OS (Figure 1a), more over it was able to prognostically differentiate patients with locally-advanced disease (stage II + III) (Figure 1b) better than the clinical staging (Figure 1c). Conclusion QOL at diagnosis predicts peri-operative mortality and long-term survival. It can help to prognostically differentiate between patients with locally advanced disease. Attempts to improve QOL prior to surgery, such as with pre-habilitation, remain an attractive area of investigation.

294 LONG TERM OUTCOMES OF THORACOSCOPIC-ASSISTED OESOPHAGECTOMY FOR EARLY OESOPHAGEAL CANCER

Abstract Oesophageal cancer is the 9th most common cancer in Scotland, yet is ranked 5th for cancer mortality. This is in part due to most new patients presenting with locally-advanced or metastatic disease. Early disease is often found during Barrett's surveillance or serendipitously. There is a paucity of literature describing the outcomes of patients who undergo resection for early disease in Europe, particularly morbidity, actual five-year survival rate, recurrence patterns and ultimate causes of death. Methods Data for fifty consecutive patients from the Royal Infirmary Edinburgh (RIE) with cN0 disease who underwent thoracoscopically-assisted McKeown (three-stage) oesophagectomy between 2005 and 2013 were recorded in a prospectively-maintained database. 20/50 were in a formal endoscopic surveillance program for Barrett’s oesophagus. Endoscopic ultrasound (EUS) became widely used at RIE in 2007 with the introduction of an endoscopic mucosal resection service, with 39/40 patients operated on since 2007 undergoing pre-operative EUS. Results Median age was 67 (range 46–81) with 34 males and 16 females. 44 had ≤pT1b, while 48 patients were pN0 (median node yield of 12). There were 4 anastomotic leaks, 4 recurrent laryngeal nerve palsies and 2 tracheo-oesophageal fistulas. There was one in-hospital death secondary to intra-operative and post-operative myocardial infarctions. As of January 2020, 16/50 patients had died, with a median survival of 9 years; five year survival was approximately 85%. 5 patients died of metastatic disease (1.3 to 6.8 years post-resection). 10 patients died of other causes, the most common being alcoholic liver disease (n = 3). Conclusion Patients in this case series received high quality surgery and peri-operative care, and survival rates were high. This dataset demonstrates that a holistic approach to healthcare is vitally important in the long-term care of such a cohort, because most deaths were not related to their cancer. This should be kept in mind when counselling patients with early disease and when liaising with their primary care provider.

The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Management of Rectal Cancer.

The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Management of Rectal Cancer.

Medullary Thyroid Cancer Patient’s Assessment of Quality of Life Tools: Results from the QaLM Study

Background: Medullary thyroid cancer (MTC) is a neuroendocrine tumour and a rare variant of thyroid cancer with different aetiology, presentation and treatment to differentiated thyroid cancer. Currently available thyroid cancer-specific quality of life (QoL) tools focus on issues and treatments more relevant to patients with differentiated thyroid cancer and therefore may not address issues specific to a MTC diagnosis and cancer journey. Method: This prospective multicentre randomised study involved 204 MTC patients completing four quality of life questionnaires (QOLQ) and stating their most and least preferred. The questionnaires were a general instrument, the EORTC QLQ-C30, two disease-specific tools, the MD Anderson Symptom Inventory (MDASI) thyroid module and the City of Hope Quality of Life Scale/THYROID (amended) and the neuroendocrine questionnaire, EORTC QLQ-GINET21. Patients were randomised to complete the four questionnaires in one of 24 possible orders and then answered questions about which tool they preferred. The primary outcome measure was patients’ preferred QoL instrument for describing their concerns and for facilitating communication with their healthcare professional. Secondary analyses looked at differences between preferred QOLQs amongst patient subgroups (WHO performance status [0 and 1+], disease stage: early [T1–3, N0 or N1A], metastatic [T4, any T N1b] and advanced [any T any N M1], and type of MTC [sporadic and inherited]), identification of MTC patients’ least preferred questionnaire and clinicians’ views on the QoL tools in terms of their ability to highlight problems not otherwise ascertained by a standard clinical review. Results: No evidence of a difference was observed for most preferred QOLQ (p = 0.650). There was however evidence of a difference in least preferred questionnaire in the cohort of 128 patients who stated their least preferred questionnaire (p = 0.042), with 36% (46/128) of patients choosing the EORTC QLQ-GI.NET21 questionnaire. Subgroup analyses showed that there was no evidence of a difference in patients’ most preferred questionnaire in sporadic MTC patients (p = 0.637), patients with WHO PS 0 or 1+ (p = 0.844 and p = 0.423) nor when comparing patients with early, advanced local or metastatic disease (p = 0.132, p = 0.463 and p = 0.506, respectively). Similarly, subgroup analyses on patients’ least preferred questionnaires showed no evidence of differences in sporadic MTC patients (p = 0.092), patients with WHO PS 0 or 1+ (p = 0.423 and p = 0.276), nor in early or metastatic disease patients (p = 0.682 and p = 0.345, respectively). There was however some evidence to suggest a difference in least preferred questionnaire in patients with advanced local stage disease (p = 0.059), with 43% (16/37) of these patients choosing the EORTC QLQ-GI.NET21 questionnaire. Conclusions: MTC patients regardless of their performance status, disease aetiology and disease burden did not express a preference for any one particular questionnaire suggesting any of the tools studied could be utilized in this patient cohort. The least preferred questionnaire being a gastrointestinal NET specific tool suggests that diarrhoea was not a significant symptom and concern for the population studied.

Metastatic head and neck cutaneous basal cell carcinomas: a retrospective observational study.

Cutaneous basal cell carcinoma is usually an indolent and slow-growing tumor with potential for local invasion and recurrence; however, metastatic events are exceedingly rare. The annual incidence of metastasis is estimated to range between 0.00281 and 0.05%. A retrospective search in the pathology database of a single tertiary institution was performed in the period between 1999 to 2019. Primary cutaneous metastatic basal cell carcinomas had paraffin blocks and glass slides retrieved. A total of 8673 cases was identified. The overall prevalence of metastatic tumors was 0.05% (4/8673). The median patient's age at diagnosis was 61yearsold (range 52-79). The most common primary site of tumor was nose (2/4) and the most common histological subtype was infiltrative. Thesampled lymph nodes were identified during primary tumor resection, except for 1 patient who had a sentinel lymph node biopsyperformed as a surgeon individual decision. One patient had hematogenous spread to the pleura, diagnosed 5years after diagnosis.In summary, this study adds new data to the current literature in metastatic primary cutaneous basal cell carcinomas and highlights the importance of early diagnosis and appropriate surgical excision in an effort to prevent local advanced disease, recurrence and lymphovascular dissemination.

Breast Cancer Survival Disparities in Mexican Women Under a Comprehensive Health Reform

PURPOSE One of the goals of Seguro Popular, Mexico’s landmark healthcare reform, was bridging the existing disparities in access to health care and health status. In 2007, this program began reimbursement of breast cancer treatment of previously uninsured Mexican women. We evaluated geographic disparities in breast cancer survival in women treated under this program and explored potential sources of heterogeneity. METHODS We classified women who were treated between 2007 and 2016 as having early (stages 0-IIA), locally advanced (stages IIB-IIIC), or metastatic (stage IV) disease. We categorized women based on a widely used marginalization index that considers education, household characteristics, rural population, and poverty levels in Mexican municipalities (low, moderate, high, and very high marginalization). We cross-linked reimbursement data with a national death registry and estimated 5-year overall survival according to clinical stage, marginalization levels, and state where women received treated. RESULTS Among 53,990 women treated for breast cancer the mean age was 52.9 years (± SD 12.4). Most patients had locally advanced disease (57.4%, n = 30,996). Early disease was more common in women with very low marginalization levels compared with women with very high levels (34% v 19%). Survival was 89.4% (95% CI: 88.8 to 89.9) for early disease, 69.8% (95% CI: 69.2 to 70.4) for locally advanced disease, and 36.1% (95% CI: 34.6 to 37.6) for metastatic disease. The least marginalized state experienced the highest survival for locally-advanced disease [76.0% (95% CI: 71.4 to 80.0)] whereas the most marginalized state experienced the lowest survival [50.2% (95% CI: 45.5 to 54.7)]. Survival in women from very highly marginalized communities was 68.7% (95% CI: 64.7 to 72.4), whereas survival in women from low marginalized communities was 74.8% (95% CI: 74.1 to 75.5). CONCLUSION In the face of a new wave of healthcare reform, Mexico will need to monitor and evaluate health disparities to achieve universal care for women with breast cancer.

Racially-Driven Diagnosis and Survival Differential in Women Diagnosed Endometrial Cancers in the United States

Objectives: The diagnosis of endometrial cancers (EC) is on the rise in the United States. In particular, African American (AA) women are being diagnosed more often with locally-advanced disease and more frequently with Type II histology. Outcomes have been observed to be worse in AA women, but whether or not race itself is a factor is not known.

Quality of surgical care can impact survival in patients with bladder cancer after robot-assisted radical cystectomy: results from the International Robotic Cystectomy Consortium

BackgroundAlthough pathological factors remain the main determinate of survival for patients with bladder cancer, quality of surgical care is crucial for satisfactory outcomes. Using a validated quality score, we investigated the impact of surgical factors on the overall survival (OS), recurrence-free survival (RFS) and disease-specific survival (DSS) in patients with locally advanced and organ-confined disease (OCD). Retrospective review of IRCC database includes 2460 patients from 29 institutions across 11 countries. The final cohort included 1343 patients who underwent RARCs between 2005 and 2016. Patients with locally advanced disease (LAD) (> pT2 and/or N +) were compared with OCD (≤ pT2/N0). Validated Quality Cystectomy Score (QCS) based on four sets of quality metrics was used to compare surgical performance. Kaplan–Meier method was used to compute RFS, CSS and OS rates. Multivariable stepwise logistic regression was used to evaluate variables associated with RFS, DSS and OS.Results48% had LAD. When compared to patients with OCD, they received neobladders less frequently (17% vs. 28%, p < 0.001) and experienced higher estimated blood loss (513 vs. 376 ml, p = 0.05). Postoperatively, more patients in the LAD group received adjuvant chemotherapy (24% vs. 4%, p < 0.001) and positive surgical margins (14% vs. 2%, p < 0.001) and had higher 90-day mortality (6% vs. 2%, p < 0.001). On multivariable analysis, female gender, higher QCS score, intracorporeal diversion, pT stage, positive lymph node status and recurrence are considered as predictors of survival. Patients with OCD exhibited better RFS, DSS and OS than patients with LAD. For patients with OCD, higher QCS was associated with improved OS but not RFS or DSS. On the other hand, patients with LAD and higher QCS exhibited higher RFS, DSS and OS when compared to those with lower QCS.ConclusionQuality of surgical care can affect disease control and OS in patients with bladder cancer treated with robot-assisted radical cystectomy.

Patient-reported outcomes (PRO) in the GARNET trial in patients (pts) with advanced or recurrent dMMR/MSI-H endometrial cancer (EC) treated with dostarlimab.

e18032 Background: PRO enable direct measurement of the experiences of patients with cancer. Anti-programmed death 1 (PD-1) therapies have shown favorable PRO in lung cancer but a data gap remains in EC. Dostarlimab is an investigational anti-PD-1 monoclonal antibody which has shown promising activity in GARNET in advanced mismatch repair deficient (dMMR) EC pts (with an ORR of 42.9% and a disease control rate of 58.6%), and a low incidence of symptomatic grade ≥3 treatment-related adverse events (anemia [2·9%], colitis [1·9%], and diarrhea [1·9%]). Here, we report on PRO measures collected from pts with dMMR/microsattelite instability high (MSI-H) EC in the single-arm GARNET trial. Methods: Pts with dMMR/MSI-H EC confirmed by local tests, with recurrent or advanced disease that progressed on a platinum regimen were enrolled. Pts received 500 mg Q3W of dostarlimab for 4 cycles, then 1000 mg Q6W until disease progression or discontinuation. PRO assessment was an exploratory endpoint and was measured by the EORTC Quality of Life Questionnaire (QLQ-C30), a validated instrument used to evaluate quality of life, functioning, disease symptoms, and treatment-related side effects. PRO were collected at each dose administration, end of treatment, and follow-up. A mixed-model for repeated measures was used to assess change from baseline, accounting for time and baseline ECOG scores. The threshold to determine clinically meaningful group-level change was ±10 points. Results: PRO data were available for 43 pts. Compliance rates were high at 98%. Relative to baseline, pts reported meaningful improvements in pain, insomnia, and social and emotional functioning over the trial duration. Appetite, nausea, vomiting, constipation, diarrhea, and physical and role functioning were stable over the trial duration. Quality of life and global health status were also maintained. Conclusions: PRO from 43 pts enrolled in the GARNET trial show that disease- and treatment-related symptoms and quality of life are improved or maintained while receiving treatment. These data, along with with the efficacy and safety profile of dostarlimab, strongly support the use of dostarlimab in dMMR/MSI-H advanced EC. Clinical trial information: NCT02715284.

The impact of a multidisciplinary approach (MA) in the management of pancreatic disease (PD).

e19196 Background: The management of PD is very insidious, mainly due to the often difficult differential diagnosis between benign and malignant diseases, and, in case of pancreatic ductal adenocarcinoma (PDCA), to the frequently hard differentiation among resectable/borderline PDCA susceptible to upfront surgery, locally advanced PDCA susceptible to a neoadjuvant approach and never resectable or metastatic PDCA in which a palliative treatment is the only option. A correct PD evaluation and the subsequent choice of the most appropriate treatment strategy, thus, need a MA, involving surgeons, oncologists, radiologists, radiation oncologists, endoscopists, gastroenterologists and pathologists. On the basis of such considerations, we investigate the impact of the multidisciplinary meeting (MM) in the management of PD at our Institution. Methods: We retrospectively evaluated all the cases discussed by surgeons at our MM. We collected data, both pre- and post-MM, regarding diagnosis (cyst vs pancreatitis vs IPMN vs PDCA), and, in case of PDCA, tumor burden at baseline (resectable vs border-line resectable vs locally advanced vs metastatic disease) and disease response to treatment (disease control vs progression). Primary endpoint was the overall rate of discrepancy in diagnosis and/or PD evaluation between pre- and post-MM. Results: From October 2018 to December 2019, a total of 139 cases were presented by surgeons. After MM, a total of 38 diagnosis and/or PD evaluation were modified, for an overall discrepancy rate of 27%. In particular, of the 38 discordant cases, 9 (24%) were initial diagnosis, 24 (63%) baseline tumor burden assessments and 5 (13%) were PDCA response evaluations. Among the 24 cases of tumor burden evaluations, treatment strategy changed in 17 out of 24 cases. More specifically, of the 19 cases, evaluated as borderline/resectable before the MM, 15 were defined as locally-advanced or metastatic disease after the MM; of the 5 cases, evaluated as not resectable before the MM, 2 were considered border-line/resectable after the MM. Similarly, out of 9 cases of discrepant initial diagnosis, 5 cases, considered as malignant disease before MM, were assessed as benign after the MM. Conclusions: Our analysis demonstrates a significant rate of discrepancy in diagnosis and/or PD evaluation between pre- and post-MM. Our results show that a MA allows a considerable modification in PD diagnosis and evaluation, maximizing the treatment strategy, in particular avoiding unnecessary and detrimental pancreatic surgery.

Treatment of metastatic recurrence of urothelial carcinoma after previous cisplatin-based chemotherapy: A retrospective comparison of different chemotherapy regimens.

e17005 Background: The optimal choice of first-line chemotherapy for urothelial carcinoma (UC) patients who recur after previous cisplatin-based chemotherapy for locally-advanced disease is unclear. Our objective is to compare the efficacy of platinum (PBC) versus non-platinum (NPBC) based first-line chemotherapy regimens for such patients after metastatic recurrence. Methods: Data was collected from the Retrospective International Study of Cancers of the Urothelial Tract (RISC), a database consisting of patients with muscle-invasive or advanced UC from 28 centers between 2005 and 2012. Patient inclusion criteria included: 1) UC with no initial metastases (cT2-4, cN0-N3, and cM0), 3) receipt of cisplatin in the locally advanced setting, and 4) receipt of chemotherapy in the first-line metastatic setting. Overall survival (OS) was the primary endpoint. Secondary endpoints included progression-free survival (PFS) and response to chemotherapy. Kaplan-Meier and Cox regression models estimated OS, PFS, and response, adjusting for age, gender, Eastern Cooperative Oncology Group (ECOG-PS), Charlson comorbidity index (CCI), surgery, T and N stage, albumin, creatinine clearance, number of initial cisplatin cycles, and time from last chemotherapy. Results: 152 patients with metastatic UC (88 PBC and 64 NPBC) were analyzed. Twelve (7.9%) patients received local definitive radiation and 7 of these 12 also underwent cystectomy. The most common NPBC regimens included taxanes, gemcitabine, or pemetrexed. The median OS was 8.70 (95% CI: 7.53 to 11.16) and 10.27 months (95% CI: 7.37 to 13.10) for PBC and NPBC (HR: 1.04, 95% CI: .67 – 1.61, p = 0.86), respectively. Multivariable analysis showed an independent prognostic effect on OS for number of previous chemotherapy cycles (3-4 vs. 1-2) (HR: 0.44, 95% CI 0.20 – 0.96, P = 0.03) and whether surgery was performed (HR: 0.44, 95% CI 0.26 – 0.75, P = 0.003). Time from last chemotherapy was not prognostic for OS (HR: 0.99, 95% CI: 0.99 – 1.00, p = 0.19). There were no significant differences for both investigator-designated PFS (HR: 0.84, 95% CI: 0.57 – 1.24, p = .39) and response to chemotherapy between PBC and NPBC (p = 0.57). Conclusions: There is no significant outcome difference between PBC vs. NPBC in patients with metastatic-recurrent urothelial carcinoma who previously received cisplatin-based chemotherapy for locally advanced disease. Those who previously underwent radical surgery or who received 3-4 cycles of cisplatin had better OS with PBC.

A Surprising Finding of Ileal Intussusception Caused by Pleural Mesothelioma Metastases

Background: Malignant pleural mesothelioma is an aggressive form of cancer originating in the pleural mesothelioma. It generally appears as a local disease in the affected hemithorax, and metastasis are rare. It is unusual for malignant pleural mesothelioma to manifest with gastrointestinal complications due to metastatic implants, but clinicians should be careful to take into consideration this hypothesis in patients with a history of malignant pleural mesothelioma referring to the Emergency Department with acute abdominal pain. Case Presentation: A 65-year-old man, with a medical history of pleural mesothelioma, presented to our emergency department for acute abdominal pain. The patient underwent abdominal ultrasound and abdominal Computed Tomography with intravenous contrast. At US examination a small bowel obstruction diagnosis was made, CT confirmed a mechanical small bowel obstruction due to an intussuscepted multiloculated mass in the terminal ileum, with CT’s signs of parietal damage; another peritoneal mass was reported adjacent to the posterior wall of the cecum and in contiguity with the iliopsoas muscle. Considering the acute medical presentation, the patient underwent surgery, with segmental bowel resection and a stapled side-by-side bowel anastomosis. Histopathology revealed metastasis of sarcomatoid pleural mesothelioma. The post-operative course was complicated by anastomotic leak treated with a conservative approach. The patient was discharged on the 24th post-operative day. Conclusion: Our case highlights the potential of pleural mesothelioma to metastasize within abdominal viscera, causing bowel obstruction. In presence of the patient’s critical clinical condition and advanced state of local disease, a surgical approach based on damage control procedure consisting in exploration, biopsies and ileostomy upstream the obstruction or, exploration and resection without anastomosis, carry on several advantages, solving the acute clinical condition, staging the disease and offering the possibility to proceed rapidly with supportive care (chemotherapy and/or surgery).

RADIANCE – Radiochemotherapy with or without Durvalumab in the treatment of anal squamous cell carcinoma: A randomized multicenter phase II trial

PurposeAnal squamous cell carcinomas (ASCC) are increasing in frequency across the developed world. The 3-year disease-free survival (DFS) in patients with locally-advanced disease is approximately 60% after primary radiochemotherapy (RCT). There is a strong rationale for combining immunotherapy with RCT in patients with ASCC due to its association with human papilloma virus (HPV) infection. Methods/designRADIANCE is an investigator initiated, prospective, multicenter, randomized phase II trial testing the addition of Durvalumab, a PD-L1 immune checkpoint inhibitor, to standard RCT in 178 patients with locally advanced ASCC (T2 ≥ 4 cm Nany, cT3-4 and/or cN+). In the control arm, patients will be treated with standard mitomycin C (MMC)/5-fluorouracil (5-FU)-based RCT. Intensity-modulated radiotherapy (IMRT) will be applied as follows: PTV_A (primary tumor) T1-T2 < 4 cm N+: 28 × 1.9 Gy = 53.2 Gy; or T2 ≥ 4 cm, T3-4 Nany: 31 × 1.9 Gy = 58.9 Gy; PTV_N (involved node): 28 × 1.8 Gy = 50.4 Gy ; and PTV_Elec (elective node): 28 × 1.43 Gy = 40.0 Gy over a period of 5,5–6 weeks. Concomitant chemotherapy will be administered using MMC with 5-FU during weeks 1 and 5 of radiotherapy (MMC 12 mg/m2, day 1 [maximum single dose 20 mg]; 5-FU 1000 mg/m2 days 1–4 and 29–32). In the experimental arm, Durvalmab (1500 mg absolute dose, intravenously) will be combined with the same RCT as in the control arm. Immunotherapy with Durvalumab will start 14 days before initiation of standard RCT, administered every four weeks (q4w) thereafter for a total of twelve doses. The primary endpoint is disease-free survival (DFS) after 3 years. DiscussionAs ASCC is considered an immunogenically “hot” tumor due to its association with HPV infection, the combination of RCT with Durvalumab may improve tumor control and long-term clinical outcome in this patient collective compared to RCT alone.

Amplifying an abscopal effect of radiation therapy with a novel immunotherapeutic agent

Abstract Radiation therapy (RT) is one of the primary treatment modalities for head and neck squamous cell carcinoma (HNSCC). At the time of diagnosis two-thirds of HNSCC patients have local-advanced disease and 50–60% of these patients will experience a local-regional or metastatic relapse within three years. Improving the immunogenic response of RT may help address this clinical problem. However, current RT regiments have failed to reliably generate robust antitumor immunity as evidenced by the rarity of clinical abscopal responses. Recently we engineered a chimeric fusion molecule called Flagrp170, a novel immunostimulatory agent highly capable of promoting antigen presentation and T-cell activation. We hypothesize that the combination of RT and Flagrp170 provides superior immunogenic signals producing effective and durable antitumor immunity against HNSCC. We report that administration of Flagrp170 to the tumor sites upon RT using a small animal radiation research platform (SARPP) results in potent activation of antigen-presenting cells, increased functionality of tumor-infiltrating T-cells, and systemic immune augmentation, when compared to either monotherapy. Additionally, the combination treatment is able to reduce the dose of RT required for tumor control and protects previously cured animals from subsequent tumor re-challenge. Finally, the combination treatment can successfully control the contralateral untreated tumors, supporting the superior activity of Flagrp170 in potentiating abscopal responses of RT. Our data suggest that the Flagrp170 may be used to enhance immunogenic cancer cell death in RT and resultant protective antitumor immunity can potentially help reduce post-RT recurrence of HNSCC.

Controversies in Rectal Cancer Treatment and Management.

Incorporation of new treatment modalities has significantly increased the complexity of the treatment and management of rectal cancer, including perioperative therapy for local advanced disease and organ preservation for those with response to the preoperative treatment. This review may help practitioners better understand the rationale and selection.

A Combination of Radiotherapy, Hyperthermia, and Immunotherapy Inhibits Pancreatic Tumor Growth and Prolongs the Survival of Mice.

Background: Pancreatic cancer (PC) is the fourth-most-deadly cancer in the United States with a 5-year survival rate of only 8%. Unfortunately, only 10–20% of PC patients are candidates for surgery, with the vast majority of patients with locally-advanced disease undergoing chemotherapy and/or radiation therapy (RT). Current treatments are clearly inadequate and novel strategies are crucially required. We investigated a novel tripartite treatment (combination of tumor targeted hyperthermia (HT), radiation therapy (RT), and immunotherapy (IT)) to alter immunosuppressive PC-tumor microenvironment (TME). (2). Methods: In a syngeneic PC murine tumor model, HT was delivered before tumor-targeted RT, by a small animal radiation research platform (SARRP) followed by intraperitoneal injections of cytotoxic T-cell agonist antibody against OX40 (also known as CD134 or Tumor necrosis factor receptor superfamily member 4; TNFRSF4) that can promote T-effector cell activation and inhibit T-regulatory (T-reg) function. (3). Results: Tripartite treatment demonstrated significant inhibition of tumor growth (p < 0.01) up to 45 days post-treatment with an increased survival rate compared to any monotherapy. Flow cytometric analysis showed a significant increase (p < 0.01) in cytotoxic CD8 and CD4+ T-cells in the TME of the tripartite treatment groups. There was no tripartite-treatment-related toxicity observed in mice. (4). Conclusions: Tripartite treatment could be a novel therapeutic option for PC patients.

PD02-05 PARTIAL NEPHRECTOMY FOR PATIENTS WITH SEVERE CKD: IS IT WORTHWHILE?

You have accessJournal of UrologyKidney Cancer: Localized: Surgical Therapy I (PD02)1 Apr 2020PD02-05 PARTIAL NEPHRECTOMY FOR PATIENTS WITH SEVERE CKD: IS IT WORTHWHILE? Diego Aguilar Palacios*, Jianbo Li, Furman Mahmood, Robert Abouassaly, and Steven C. Campbell Diego Aguilar Palacios*Diego Aguilar Palacios* More articles by this author , Jianbo LiJianbo Li More articles by this author , Furman MahmoodFurman Mahmood More articles by this author , Robert AbouassalyRobert Abouassaly More articles by this author , and Steven C. CampbellSteven C. Campbell More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000822.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Partial nephrectomy (PN) is prioritized over radical nephrectomy (RN) in patients with CKD whenever feasible. However, we hypothesized that some patients with severe CKD might rapidly progress to end stage renal disease (ESRD), in which case the morbidity that can be associated with PN would not be justified. METHODS: Retrospective review of all 62 patient with stage IV CKD undergoing PN (1999-2015) was performed to evaluate preoperative/intraoperative factors and postoperative outcomes. ESRD was defined as postoperative initiation of permanent dialysis or eGFR<15ml/min/1.73m2. Survival analyses were used to evaluate factors associated with time to progression to ESRD. RESULTS: Median age was 67 years, 71% of patients were male and 84% were Caucasian. Comorbidities included hypertension (94%), cardiovascular disease (53%), diabetes (32%), and tobacco use (58%), and median preoperative eGFR was 23 ml/min/1.73m2. Open PN was performed in 45 patients (73%). Benign pathology was found in 10 patients (16%) and 7 had locally-advanced disease (11%). Unfavorable perioperative outcomes occurred in 15 patients (24%) defined as 90 day-mortality (3%), postoperative Clavien complication ≥IIIb (14%), or positive surgical margin (12%). Median time to progression to ESRD was only 27 months, and only 14 months in patients with preoperative GFR<20ml/min/1.73m2. In contrast, median time to progression to ESRD was 58 months in patients with preoperative GFR>25. On multivariable analysis African-American race [HR: 2.55 (1.10-5.95)], preoperative eGFR 20-25 or <20 [HR: 2.59 (1.16-5.84) and 5.03 (2.03-12.44), respectively] and minimally invasive approach [HR:2.05 (1.01-4.19)] were independently associated with progression to ESRD. CONCLUSIONS: Our data suggest that patients with stage IV CKD undergoing PN tend to have substantial comorbidities and are at risk for unfavorable perioperative outcomes and rapid progression to ESRD. Alternate strategies such as renal mass biopsy for oncologic risk stratification, active surveillance, or RN (either upfront or after progression to ESRD) may be more appropriate, particularly if PN is high complexity and African-American or when preoperative GFR<25. Source of Funding: None © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e67-e68 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Diego Aguilar Palacios* More articles by this author Jianbo Li More articles by this author Furman Mahmood More articles by this author Robert Abouassaly More articles by this author Steven C. Campbell More articles by this author Expand All Advertisement PDF downloadLoading ...

Pneumonectomy for lung metastases: the role in the modern era

Lung metastasectomy is considered worldwide as part of multimodal treatment for selected oligometastatic patients. Wedge resection is the most common approach performed with lung-sparing intent and, even if anatomical resections like segmentectomies or even lobectomies can be accepted, the role of pneumonectomy has always been debated and progressively discouraged due to the perceived high morbidity and mortality rates compared with its uncertain oncological benefits. A retrospective review and analysis of patients underwent pneumonectomy for lung metastases conducted in our center from January 1995 to December 2017 showed that on a total of 832 pneumonectomies performed, only 17 (2%) were conducted to resect pulmonary metastases and above all, only two patients were operated in the last decade. This revealed the tendency to progressively abandon the use of pneumonectomy to treat pulmonary metastasis. Indications and outcomes of pneumonectomy to resect pulmonary metastases are illustrated along with the speculative reasons of the decrease in the use of this therapeutic tool. The latter include a better patient selection due to the improved understanding of the oligometastatic disease, major improvements in the efficiency and tolerance of systemic therapies and the availability of alternative techniques for the local treatment of secondary lung lesions. Nevertheless, the limited benefit in terms of long-term survival and the relative high morbidity and mortality should not exclude a priori from considering pneumonectomy with curative intent for locally-advanced metastatic disease. A tiny role for this option is likely to remain in the therapeutic armamentarium for highly selected patients with isolated resectable pulmonary metastases undergoing a multidisciplinary management when no other alternatives are available.

Akciğer Karsinomu Tedavisi Sırasında Beyin Metastazı Gelişimini Etkileyen Faktörler

INTRODUCTION: Brain metastases are frequently seen in lung carcinomas and increase mortality. The aim of this study is to evaluate the factors affecting brain metastases occurrence and to determine survival after brain metastases in patients with lung cancer. METHODS: The study included 72 patients who were diagnosed with lung carcinoma and had no brain metastasis at the time of diagnosis. RESULTS: The diagnosis of adenocarcinoma was 40.3%, while small cell lung carcinoma (SCLC) was 31.9% and squamous cell carcinoma was 26.4%. At the time of diagnosis 30.6% of patients were in stage IVB, 29.2% in stage IIIB and 18.1% in stage IIIA group. There were 5 (6.9%) patients in stage I and II. N2 involvement was found in 66.7% of the patients and N3 involvement was found in 23.6% of the patients. In the initial diagnosis, distant metastasis was not present in 63.9% of the patients. The time to brain metastasis development was 10.0 months. The survial of the patients was 2.0 months after the development of brain metastasis. Only 8,3% (n: 6) of the patients are still alive. All these alive patients were diagnosed as adenocarcinoma. DISCUSSION AND CONCLUSION: In our study, despite the adequate treatment responses in the primary tumor, brain metastasis developed in the patients within one year and caused loss of life in two months. Mediastinal lymph node involvement, local advanced and metastatic stage disease and adenocancer histology are effective factors in the development of brain metastasis in lung carcinoma.

Utilization of Adjuvant Radiotherapy for Resected Colon Cancer and Its Effect on Outcome.

Adjuvant radiation is generally not recommended for colon cancer but may be considered in certain clinical scenarios [advanced local disease (pT4) and/or positive margins]. Guidelines in this area are lacking; thus we analyzed the National Cancer Database (NCDB) for patterns of care in this regard and any predictors for outcome. We queried the NCDB from 2004 to 2016 for patients with resected adenocarcinoma of the colon having pT4 and/or had positive margins on final pathology and who received adjuvant multiagent chemotherapy. Multivariable logistic regression was used to identify predictors of adjuvant radiation. A propensity score was used to perform matched Kaplan-Meier analysis. Propensity-adjusted Cox regression was used to identify predictors of overall survival. We identified 23,325 patients meeting criteria, of whom 1711 (7%) received adjuvant radiation. Median follow-up was 36months. The majority of patients were pT4 alone (65%). Predictors of adjuvant radiation were lower comorbidity score, younger age, more remote year of treatment, and both pT4 and positive margins. Kaplan-Meier analysis revealed improved overall survival (OS) in patients with both pT4 and positive margins treated with radiation (median OS: 66 versus 47months, p = 0.02). Receipt of adjuvant radiation was associated with improved OS [hazard ratio (HR): 0.86 (0.80-0.93) p = 0.0002] on Cox regression analysis. Increased age, higher comorbidity score, lower income, government insurance, and combined pT4/positive margins were indicative of worse survival. Expectedly, adjuvant radiation use was relatively low but was associated with improved OS in patients with both pT4 and positive margins.