Sites Of Residual Disease Research Articles

Psoriasis with Leg Involvement as the New Difficult-To-Treat Area: A Cohort Study of Patients Treated With Risankizumab.

Historically, difficult-to-treat areas in psoriasis included face, scalp, folds, genitalia, nails, and palmoplantar region. Recent studies have found that lower limbs behave like a "new" difficult-to-treat area as they can be the only site of residual disease even in patients undergoing biologic therapies. We aimed to evaluate whether legs had different response rates and response times to treatment with a new biologic drug, risankizumab, compared to other body sites. We conducted a real-life, observational, retrospective, multicenter study including patients affected by moderate-to-severe psoriasis with leg involvement and undergoing biological therapy with risankizumab for more than 16 weeks. The Psoriasis Area Severity Index (PASI) and Leg-PASI were collected at T0 and at weeks 16, 28, 40, 52, 64, and 76. Statistical analysis using Student's t test and linear regression analysis were performed. A total of 124 patients were included. The difference between the improvement percentage compared to baseline was statistically significant at weeks 16 and 28, demonstrating that Leg-PASI improved less than PASI. From the linear regression it was deduced that the slope is statistically less steep for Leg-PASI than for overall PASI, confirming that this site responds more slowly to the therapy. Leg response to risankizumab appears to differ significantly from other body sites in the first weeks of treatment, even if after 28 weeks, statistical significance is lost. Our preliminary finding suggests that risankizumab can be considered an effective treatment for leg psoriasis but with longer response times than other areas, demonstrating the relative nature of resistance to treatment of this district.

Phase II study of multidisciplinary therapy combined with pembrolizumab for patients with synchronous oligometastatic non-small cell lung cancer TRAP-OLIGO study (WJOG11118L): Feasibility analysis of induction therapy and local ablative therapy.

8564 Background: Several clinical trials have shown that local ablative therapy (LAT) to all sites of the disease might provide survival benefit for patients with oligometastatic non-small cell lung cancer (NSCLC). Few studies have evaluated feasibility of multiciliary therapy combined immune-checkpoint inhibitor plus chemotherapy with LAT to all sites of disease. Methods: This multicenter, single-arm, phase II trial enrolled untreated patients with stage IV NSCLC who had 3 or fewer metastatic lesions. All patients had received 2–4 cycles of a systemic treatment including pembrolizumab and platinum-doublet chemotherapy as induction therapy. LAT was administered to all residual lesions after induction therapy, followed by maintenance therapy including pembrolizumab. The primary endpoint is the progression-free survival (PFS) rate of 24 months from the date of initiation of LAT. The secondary endpoints are safety, response rate of induction therapy, PFS, overall survival, and proportion of implementation. The present analysis showed feasibility of induction therapy and LAT. Results: Between October 30, 2020, and August 12, 2022, 30 patients were enrolled. The number of metastases at diagnosis was one in 7 patients (7/30, 23%), two in 14 patients (14/30, 47%), and three in 9 patients (9/30, 30%). All patients received induction therapy, and the objective response rate was 21/30, 70% (95% confidence interval, 50% to 85%). Adverse events of grade 3/4 occurred in 21/30, 70%, including neutropenia (5/30, 17%), anemia (2/30, 7%), and thrombocytopenia (2/30, 7%). Seven patients did not receive planned LAT for the following reasons: disease progression (N=3), adverse events (N=2; pneumonitis grade 2, and hepatitis grade 3), sudden death (N=1), and one patient had proven stage III after induction therapy. Twenty-three patients (23/30, 77%) received planned LAT to all sites of residual disease. As LAT, five patients received surgery only, 12 patients received radiotherapy only, and 6 patients received both surgery and radiotherapy. Eighteen patients completed planned radiotherapy for 32 lesions (primary sites 22%, lymph node 25%, bone 25%, pulmonary metastasis 19%, brain 6% and adrenal 3%). Eleven patients received surgery (primary sites and lymph node) as LAT. Grade 3/4 adverse events during LAT occurred in 3 patients (3/23, 13%): rash (n=1), hypoxia (n=1) and CPK increased (n=1). There were no treatment-related deaths. Conclusions: Results of the TRAP-OLIGO study showed that multimodality treatment with platinum-based chemotherapy plus pembrolizumab and LAT had favorable implementation, and planned LAT was feasible in this population. Clinical trial information: jRCTs041200046 .

Unradical Surgery for Locally-Advanced Thymoma: Is it time to evolve Perspectives?

ObjectivesNearly-one-third of thymomas are locally-advanced at diagnosis. The traditional dogma that surgery is justified in case a complete resection can be achieved has remained unmovable until today. This study aimed to investigate feasibility and oncologic efficacy of incomplete resection for locally-advanced thymomas in a contest of multimodality therapy. Materials and MethodsA retrospective analysis was conducted using data of prospectively maintained thymomas database in a single high-volume centre. Data on 285 consecutive patients undergoing surgery for stage III and IVa thymomas between 1995 and 2019 were reviewed. Patients who underwent incomplete resection with curative-intent (removal of at least 90% of tumour burden) were included. Long-term outcomes and predictors of cancer-specific survival (CSS) and progression-free survival (PFS) were analyzed. Secondary endpoint was to assess adjuvant therapy efficacy. ResultsThe study included 79 patients, 60 with microscopic residual tumour (76%, R1) and 19 with macroscopic residual disease (24%, R2). Masaoka-Koga stage was: III in 41 patients (52%) and IVa in 38 (48%). Histology was B2-thymomas (n = 31, 39.2%) followed by B3 (n = 27, 34.2%). Five- and 10-years CSS was 88% and 80%. Seventy patients (90%) underwent adjuvant treatment; they showed CSS comparable to radical resected patients (5-years: 89.1% vs 98.9%, respectively; 10-years: 81.8% vs 92.7%, respectively, p = 0.43). The site of residual disease, Masaoka-Koga stage and WHO histology did not affect prognosis. Stepwise multivariable analysis confirmed adjuvant therapy as a favourable CSS prognostic factor (HR, 0.51; 95% CI, 0.33–0.79, p = 0.003). Stratifying by subgroups, R2-patients who received postoperative chemo(radio)therapy (pCRT) showed a significantly better prognosis than R2-patients treated by consolidation radiotherapy alone (10-years CSS: 60%, p < 0.001). ConclusionIn locally-advanced thymomas, whenever a radical surgery cannot be achieved, incomplete resection has proved to be effective in a contest of multimodality strategy, independently of WHO histology, Masaoka-Koga stage and site of residual disease.

891P Naxitamab treatment for relapsed or refractory high-risk neuroblastoma: Outcomes from the first prespecified analyses of the Pivotal 201 Trial

Naxitamab is a humanized GD2-binding monoclonal antibody approved in the US with GM-CSF for the treatment of relapsed/refractory high-risk neuroblastoma (HR-NB) in the bone/bone marrow (BM). This accelerated approval was based in part on an ad hoc analysis of data from the registrational phase II 201 trial (NCT03363373). Here we report the first results of a prespecified analysis from this same trial. Trial 201 is an ongoing phase II trial evaluating naxitamab+GM-CSF in patients with relapsed/refractory HR-NB with residual disease limited to bone/BM. Patients with progressive or residual soft tissue disease were not eligible. Naxitamab was administered over 30-60 min in the outpatient setting on Days 1/3/5 with GM-CSF on Days –4 to 5; cycles were 28 days. Efficacy was evaluated by independent pathology and radiology review per revised International Neuroblastoma Response Criteria. Assuming an actual overall response rate (ORR; complete response [CR] + partial response [PR]) of 45%, a sample size of 37 patients was considered sufficient to ensure ≥90% power to exclude an overall response rate of ≤20% at an α-level of 0.05. At data cutoff (Dec 31, 2021) there were 52 patients in the efficacy population and 74 in safety. The ORR was 50.0% (26/52; 95% CI 36-64%) with a CR rate of 38.5% (95% CI 25-53%). The trial met the primary endpoint for the prespecified analysis as the lower 95% CI for ORR was >20%. Disease control rate (CR+PR+minor response+stable disease) was 78.8% (41/52; 95% CI 65-89%) The adverse event (AE) profile was like previous reports with most being infusion-related reactions including hypotension and pain. 44.6% (33/74) of patients experienced ≥1 treatment-emergent serious AE; 6.8% (5/74) patients discontinued naxitamab due to treatment-emergent AEs. There were no deaths related to naxitamab. Based on this prespecified analysis, naxitamab provides a significant and clinically relevant response in patients with relapsed/refractory HR-NB limited to bone/BM – frequent sites of residual disease. These efficacy results combined with a manageable safety profile demonstrate that naxitamab addresses a significant unmet medical need.

Naxitamab (NAX) treatment for refractory/relapsed (R/R) high-risk neuroblastoma (HR-NB): Response data and efficacy in patient (pt) subgroups.

e22019 Background: Almost half of pts with NB present with high-risk disease, most of whom experience persistence of disease or disease progression. Further, residual disease in the bone/bone marrow (BM) can drive relapse. NAX is a humanized GD2-binding monoclonal antibody indicated under accelerated approval in the US with GM-CSF for the treatment of R/R HR-NB in the bone/BM in pts ≥1 year of age with a partial response (PR), minor response (MR), or stable disease (SD) to prior therapy. Here we characterize the response data of NAX overall and efficacy in pt subgroups. Methods: Trial 201 is an ongoing registrational phase II trial evaluating NAX in pts with R/R HR-NB. Pts with progressive or residual soft tissue disease were excluded. NAX was administered over 30-60 min in the outpatient setting on Days 1/3/5 at 3 mg/kg/day with GM-CSF at 250 µg/m2/day on Days –4 to 0 and 500 µg/m2/day on Days 1 to 5; cycles were every 4 wks. Efficacy was evaluated by independent pathology and radiology review per revised International Neuroblastoma Response Criteria. Results: Results presented here are from an ad hoc interim analysis (Aug 5, 2020) of 48 pts (safety population) and 36 (efficacy population). Pts in the efficacy population received a median of 7 cycles (range 1–11). Overall response rate (ORR; complete response [CR] + PR) was 58% (44% CR; Table). Of the 9 responders who had PR initially, 4 improved to CR. Median number of cycles before onset of response (CR or PR) was 2 (range 2–8) and median time to onset of response (CR or PR) was 7.3 wks (95% CI 6–17). Median duration of response was 24.9 wks (95% CI 25–not estimable). The most common adverse events (CTCAE graded) were infusion-related reactions including hypotension and pain, which occurred in 98% and 96% of pts, respectively. Adverse events were managed with established guidelines. Conclusions: NAX provided a clinically meaningful response in pts with R/R HR-NB limited to bone/BM – frequent sites of residual disease. Response rates were generally consistent across subgroups. These efficacy results combined with a manageable safety profile and use in the outpatient setting demonstrate that NAX addresses a significant unmet medical need. Clinical trial information: NCT03363373. [Table: see text]

Association between oligo-residual disease and patterns of failure during EGFR-TKI treatment in EGFR-mutated non-small cell lung cancer: a retrospective study

BackgroundLocal ablative therapy (LAT) may be beneficial for patients with epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC) with oligo-residual disease after treatment with EGFR tyrosine kinase inhibitor (EGFR-TKI). However, this has not been fully established. This study aimed to evaluate the predominant progressive disease (PD) pattern limited to residual sites of disease after treatment with EGFR-TKI.MethodsPatients with advanced EGFR-mutated NSCLC treated with EGFR-TKIs as first-line therapy were retrospectively analysed during a 7-year period. Oligo-residual disease was defined as the presence of 1 – 4 lesions (including the primary site) at 3 months from the start of EGFR-TKI treatment. The predictive factors of PD patterns after EGFR-TKI treatment were evaluated.ResultsA total of 207 patients were included. Three months after the start of EGFR-TKI treatment, 66 patients (32%) had oligo-residual disease. A total of 191 patients had PD, 60 with oligo-residual disease and 131 with non-oligo-residual disease. Regarding the pattern, 44 patients (73%) with oligo-residual disease and 37 patients (28%) with non-oligo-residual disease had PD limited to the residual sites. Multivariate logistic regression analysis at 3 months from the start of EGFR-TKI treatment revealed that oligo-residual disease (P < 0.001), the lack of residual central nervous system metastases (P = 0.032), and initial treatment with osimertinib (P = 0.028) were independent predictors of PD limited to residual disease sites.ConclusionsThis study provided a rationale for LAT to all sites of residual disease in patients with oligo-residual disease during EGFR-TKI treatment.

Anatomic patterns of relapse and progression following treatment with 131 I-MIBG in relapsed or refractory neuroblastoma.

Patients with metaiodobenzylguanidine (MIBG)-avid relapsed or refractory neuroblastoma after initial therapy may exhibit transient responses to salvage treatment with iodine-131 metaiodobenzylguanidine (131 I-MIBG). It is unclear whether disease progression following 131 I-MIBG treatment occurs in previously involved versus new anatomic sites of disease. Understanding this pattern of relapse will inform the use of consolidation therapy following 131 I-MIBG administration. Patients with relapsed or refractory metastatic MIBG-avid neuroblastoma or ganglioneuroblastoma, who received single-agent 131 I-MIBG, had stable or responding disease 6-8weeks following 131 I-MIBG, but subsequently experienced disease progression were included. MIBG scans were reviewed to establish anatomic and temporal evolution of MIBG-avid disease. A total of 84 MIBG-avid metastatic sites were identified immediately prior to MIBG therapy in a cohort of 12 patients. At first progression, a total of 101 MIBG-avid sites were identified, of which 69 (68%) overlapped with pre-treatment disease sites, while 32 (32%) represented anatomically new disease areas. Eight of 12 patients had one or more new MIBG-avid sites at first progression. Of the 69 involved sites at progression that overlapped with pre-treatment disease, 11 represented relapsed sites that had cleared following MIBG therapy, two were persistent but increasingly MIBG-avid, and 56 were stably persistent. Previously involved anatomic disease sites predominate at disease progression following 131 I-MIBG treatment. Nevertheless, the majority of patients progressed in at least one new anatomic disease site. This suggests that consolidation focal therapies targeting residual disease sites may be of limited benefit in preventing systemic disease progression following 131 I-MIBG treatment of relapsed or refractory neuroblastoma.

Efficacy of naxitamab in patients with refractory/relapse (R/R) high-risk neuroblastoma (HR-NB) by bone/bone marrow (BM) evaluation, potential sites of residual disease.

10022 Background: NB is the most common extracranial solid tumor in children and half of patients present with high-risk disease. Bone and BM are frequent sites of metastatic disease and can serve as a reservoir for residual disease driving relapse. Naxitamab, a GD2-binding monoclonal antibody, was recently approved in the United States in combination with GM-CSF for the treatment of pediatric patients ≥1 year of age and adult patients with R/R HR-NB in the bone/BM who have demonstrated a partial response (PR), minor response (MR), or stable disease (SD) to prior therapy. Here we describe outcomes from the registrational Trial 201 (NCT03363373) detailed by bone/BM involvement. Methods: HR-NB patients with primary refractory disease or incomplete response to salvage treatment following relapse or progressive disease (PD) (in both cases including SD, MR and PR) with disease limited to bone and/or BM were eligible. Naxitamab was administered over ≥30 min in the outpatient setting on Days 1, 3 and 5 at 3 mg/kg/infusion (9 mg/kg/cycle) in combination with GM-CSF at 250 µg/m2/day on Days -4 to 0 and at 500 µg/m2/day on days 1 to 5. Treatment cycles were repeated every 4 weeks. Response was assessed after Cycle 2 and then every 2-3 months by revised International Neuroblastoma Response Criteria (INRC) using BM biopsies/aspirates and 123I-MIBG scintigraphy or FDG-PET. Effectiveness was concluded if the lower limit of the Clopper-Pearson exact 95% confidence interval (CI) of overall response rate (ORR) was &gt;20%. We report efficacy data on 22 patients and safety data on the first 25 patients enrolled. Results: 13 (59%) patients had NB in bone, 2 (9%) had NB in BM, and 7 (32%) had NB in both bone and BM. Summary of overall response and response by compartment. Conclusions: Naxitamab provided clinically meaningful activity in both bone and BM with ORR of 68% and had a manageable AE profile. Clinical trial information: NCT03363373. [Table: see text]

Greater-omentum lesion-score (GOLS) as a predictor of residual disease in different regions of the peritoneal cavity in patients undergoing interval cytoreductive surgery for advanced ovarian cancer and its potential clinical utility

Background and aimThe greater omentum(GO) is a common site of residual disease in patients receiving neoadjuvant chemotherapy for advanced epithelial ovarian cancer. The presence of tumor in the GO could predict presence of disease in other peritoneal regions. The goal of this study was to perform a correlation between the greater-omentum lesion-score(GOLS) and presence of disease in different peritoneal regions and determine its potential utility in guiding interval cytoreductive surgery(CRS). MethodsThis prospective study included 134 patients undergoing interval CRS from July 1, 2018 to June 30, 2020.Each region of Sugarbaker's Peritobneal Cancer Index(PCI) was given a lesion score(LS) from 0 to 3 according to the diameter of the largest tumor in the region. The GOLS was recorded separately from other structures in the region. Correlation between the GOLS and surgical and pathological LS in each region was performed. ResultsAs the GOLS increased, the incidence of disease(surgical LS) in other regions of the peritoneal cavity increased. Receiver operating characteristic(ROC) curves showed area under curve more than 80% for regions 1–2 and 7–8 indicating a high probability of disease in these regions in patients with GOLS 1–3. The positive predictive value(PPV) of preoperative imaging for GOLS was 95.7%. No cut-off of the GOLS could predict presence of disease on pathology with more than 70% accuracy. ConclusionsPresence of disease in the GO warrants performing upper abdominal exploration and/or cytoreduction and interval CRS should be planned accordingly in these patients. Imaging has a high PPV in detecting disease in the GO.

The spleen as a sanctuary site for residual leukemic cells following ABT-199 monotherapy in ETP-ALL

AbstractB-cell lymphoma 2 (BCL-2) has recently emerged as a therapeutic target for early T-cell progenitor acute lymphoblastic leukemia (ETP-ALL), a high-risk subtype of human T-cell ALL. The major clinical challenge with targeted therapeutics, such as the BCL-2 inhibitor ABT-199, is the development of acquired resistance. We assessed the in vivo response of luciferase-positive LOUCY cells to ABT-199 monotherapy and observed specific residual disease in the splenic microenvironment. Of note, these results were confirmed by using a primary ETP-ALL patient-derived xenograft. Splenomegaly has previously been associated with poor prognosis in diverse types of leukemia. However, the exact mechanism by which the splenic microenvironment alters responses to specific targeted therapies remains largely unexplored. We show that residual LOUCY cells isolated from the spleen microenvironment displayed reduced BCL-2 dependence, which was accompanied by decreased BCL-2 expression levels. Notably, this phenotype of reduced BCL-2 dependence could be recapitulated by using human splenic fibroblast coculture experiments and was confirmed in an in vitro chronic ABT-199 resistance model of LOUCY. Finally, single-cell RNA-sequencing was used to show that ABT-199 triggers transcriptional changes in T-cell differentiation genes in leukemic cells obtained from the spleen microenvironment. Of note, increased expression of CD1a and sCD3 was also observed in ABT199-resistant LOUCY clones, further reinforcing the idea that a more differentiated leukemic population might display decreased sensitivity toward BCL-2 inhibition. Overall, our data reveal the spleen as a site of residual disease for ABT-199 treatment in ETP-ALL and provide evidence for plasticity in T-cell differentiation as a mechanism of therapy resistance.

Distribution of residual disease in the peritoneum following neoadjuvant chemotherapy in advanced epithelial ovarian cancer and its potential therapeutic implications

IntroductionResidual disease in ‘normal appearing’ peritoneum is seen in nearly 30% of the patients following neoadjuvant chemotherapy (NACT) for advanced ovarian cancer. The goal was to study the sequence of response in different regions, the commonest sites of occult residual disease, its incidence in different peritoneal regions and the potential therapeutic implications of these. MethodsThis was a prospective multi-centre study (July 2018–June 2019). Pathological evaluation of cytoreductive surgery specimens was performed according to a fixed protocol. Prevalence of residual disease in different regions was used to study patterns of response and distribution of residual disease. ResultIn 85 patients treated between July 2018 to June 2019, microscopic disease in ‘normal appearing’ peritoneal regions was seen in 22 (25.2%) and in normal peritoneum around tumor nodules in 30 (35.2%) patients. Regions 4 and 8 of Sugarbaker’s PCI had the highest incidence of occult disease and regions 9 and 10 the lowest. The response to chemotherapy occurred in a similar manner in over 95%- the least common site of residual disease was the small bowel mesentery, followed by upper regions (regions 1–3), omentum and middle regions (regions 0, 4, 8), lower regions (regions 5–7) and lastly the ovaries. ConclusionsDuring interval CRS, based on the disease mapping provided in this manuscript, regions that have a high probability of residual disease should be explored and dissected. Complete resection of involved the peritoneal region can completely address the occult disease. The role of resection of the entire region as well as ‘normal appearing’ parietal peritoneal regions should be prospectively evaluated.

Abstract A01: Specific targeting of adipose tissue-associated metastasis using bile salt nanoparticles

Abstract Purpose: Mortality in ovarian cancer occurs in the setting of recurrent disease. Recurrent disease is known to arise from residual disease, which persists after the conclusion of standard of care, consequently rebuilding the tumor. Adipose tissue provides cancer cells with a unique microenvironment that can enhance survival by upregulating antiapoptosis genes or by decreasing drug bioavailability. Indeed, adipose-rich organs such as the omentum are not only preferential sites for metastasis but also main sites of residual disease in ovarian cancer. We hypothesized that targeting adipose-rich tissues could limit residual disease and prevent recurrence. Thus, the objective of this study was to develop effective drug delivery platforms that can specifically target residual disease in adipose-rich tissues. Methods: The delivery system is a nanoparticle platform composed of polymerized ursodeoxycholic acid (PUDCA) synthesized by esterification of UDCA monomer. Paclitaxel (PTX) or deep-infrared FL dye (DIR) was encapsulated to a final concentration of 24 ug or 5 mg per mg PUDCA, respectively. In vitro dose response studies were performed using mCherry+ human OCSC1-F2 ovarian cancer cells for 72 h. DMSO-resuspended PTX (DMSO-PTX) was used as control. In vivo studies were performed in athymic nude mice bearing i.p. tumors from mCherry+ OCSC1-F2 cells. For biodistribution studies, DIR-PUDCA was administered as one-time i.p. injection of 1.3 mg of DIR-PUDCA followed by ex vivo measurement of FL intensity after 14 days. DMSO-resuspended DIR (DMSO-DIR) was used as control. For efficacy studies, the groups were: (1) vehicle control; (2) taxol (PTX in Cremaphor; 12mg/kg) + DMSO-PTX (31.2 ug PTX); and (3) taxol + PUDCA-PTX. Treatment was administered i.p. twice a week for a total of 4 doses. Tumor burden and residual disease were determined by quantification of mCherry ROI FL area. Results: PUDCA-PTX demonstrated significantly improved efficacy both in vitro and in vivo. PUDCA-PTX demonstrated a six-fold reduction in in vitro GI50 compared to DMSO-PTX (23.04 nM PUDCA-PTX vs. 137.2 nM DMSO-PTX). Biodistribution studies showed delivery of DIR specifically to adipose-rich tissues (DIR mean FL intensity (MFI) for greater and lesser omentum = 76570±17808 vs. mesentery MFI = 22326±2956; p = 0.0297). Efficacy studies showed that PUDCA-PTX was significantly more effective in inhibiting tumor progression (p = 0.0191) and, more importantly, in preventing recurrent disease compared to DMSO-PTX. Finally, PUDCA-PTX was able to significantly reduce omental-residual disease compared to DMSO-PTX (p=0.049). Conclusion: We demonstrate for the first time that PUDCA is able to target residual disease localized in adipocyte-rich tissues and that this significantly delays tumor progression and prevents recurrence. These results underscore the value of i.p.-delivered PUDCA as a drug delivery platform for enhanced targeting of cancer cells within adipose-rich tissues and its value in the management of ovarian cancer patients. Citation Format: Roslyn Tedja, Ayesha B. Alvero, Jung Seok Lee, Mary Pitruzzello, Tarek Fahmy, Gil G. Mor. Specific targeting of adipose tissue-associated metastasis using bile salt nanoparticles [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr A01.

Extent and distribution of peritoneal disease in patients undergoing cytoreductive surgery for first platinum sensitive recurrence in ovarian cancer and its potential therapeutic implications

BackgroundSelected patients with platinum sensitive recurrent ovarian cancer may benefit from cytoreductive surgery (CRS). The aim was to study the pattern of peritoneal involvement in these patients that has not been done before. MethodsA comparison was made between the surgical and pathological findings in 60 patients undergoing salvage CRS from July 2018 to December 2019. The sites of residual disease, correlation with surgical and pathological peritoneal cancer index (PCI), small bowel involvement and regional lymph node involvement were studied. ResultsFifty-eight (96.6%) had serous carcinoma and 2 (3.4%) clear cell carcinoma. The median surgical PCI (sPCI) was 7 [range 0–27] and median pathological PCI (pPCI) 4 [range 0–21]. CC-0 resection was performed in 81.6%. The upper regions (region 1,2,3) were the commonest sites of residual disease (63.3%) followed by lower regions (region 5,6,7) in 55.0%, middle regions (regions 0,4,8) in 53.3% and small bowel regions (regions 9–12) in 26.6%. Small bowel involvement was associated with a higher sPCI and pPCI (p < 0.001 for both). Regional nodes were involved in 46.6%. A pathological complete response was seen in 8 (13.3%) patients of which 2 had residual disease in regional nodes. Microscopic disease in ‘normal appearing’ peritoneum was seen in 21%. ConclusionsThe parietal peritoneum was the commonest site of recurrence. Small bowel involvement occurred late and was associated with more extensive disease. Regional lymph node involvement was seen nearly 50% and was a common site for occult disease. The role of more extensive parietal peritoneal resection for recurrent disease should be evaluated prospectively.

The Endoscopic Relationship of the Stapedius Muscle to the Facial Nerve: Implications for Retrotympanic Surgery.

The stapedius muscle, tendon, and pyramidal eminence are structures within the retrotympanum. In cholesteatoma surgery, the retrotympanum is a common site of residual disease. The removal of the pyramidal eminence during surgery is sometimes necessary to obtain better visualization of the superior retrotympanum during surgery. Understanding the relational anatomy of structures in the region to the facial nerve allows the surgeon to safely access regional disease. This study aims to better understand the anatomical relationship between the mastoid portion of the facial nerve, the pyramidal eminence, and the stapedius muscle. A secondary aim is to demonstrate that removal of the stapedius muscle in the cadaver model, can increase exposure to the retrotympanic space. Anatomical cadaveric observation study. Endoscopic dissection of cadaveric heads was undertaken. Classification of the superior and inferior retrotympanic area was performed. The anatomy of the stapedius muscle was described including relationships, depth, course, and angle with respect to the facial nerve. The pyramidal eminence and stapedius muscle were removed in all specimens and the exposure of the retrotympanum re-evaluated to determine if exposure of the region was increased. In all cases (11 ears), the stapedius muscle was located medial and anterior to the mastoid portion of the facial nerve, with the second genu superior. The mean antero-posterior distance from the apex of the pyramidal eminence, which the stapedius tendon enters, to the stapes itself was 4.10 mm (range, 2.92-5.73 mm; standard deviation [SD] 0.90 mm). In all cases, irrespective of sinus tympani conformation, removal of the pyramidal eminence and stapedial bony crest in proximity to the facial nerve allowed exposure of the whole retrotympanic region, using a 0-degree endoscope. The pyramidal eminence and stapedius muscle have a relatively constant relationship to the facial nerve. Removal of the stapedius muscle in the human cadaver model increases the exposure of the sinus tympani and subpyramidal space. Increased visualization in this region, may reduce risk of residual cholesteatoma in patients.

Right Upper Abdominal Resections in Advanced Stage Ovarian Cancer.

The right upper abdominal involvement is frequently encountered in patients with advanced stage ovarian cancer. The aim of this paper is to study the safety and efficacy of extended resections at this level as well as to determine the sites of residual disease. Between January 2016 and December 2019, 26 patients submitted to right upper abdominal resections were identified. Peritoneal stripping and full thickness resections were the most commonly performed resections (in 57% and 19% of cases, respectively), followed by capsular liver resection and atypical liver resection (in 30% and 23% of cases, respectively) while the most common sites where resection was incomplete were the liver pedicle and porta hepatis. Exceptionally, one case necessitated performing a pancreatoduodenectomy as part of debulking surgery. Postoperatively, two cases developed serious complications and required reintervention; however, the overall mortality was null. Right upper abdominal resections seem to be feasible and effective in order to maximize the debulking effort with acceptable risks arising from perioperative complications.

Secondary debulking for ovarian carcinoma relapse: The R-R dilemma – is the prognosis different for residual or recurrent disease?

Objective:To analyze the kind of ovarian cancer relapse by separating residual from recurrent disease and correlating them with patient survival.Material and Methods:This was a retrospective study of 200 women with ovarian carcinoma relapse between 2005 and 2017.Results:The main sites of residual disease included the great omentum, epiploic appendices, liver round ligament, gallbladder, and cervical/vaginal stump. The median survival for women with residual disease treated with cytoreductive surgery (CRS) + hyperthermic intraperitoneal chemotherapy (HIPEC) + systemic chemotherapy was 38 months compared with the control group, which reached 23.8 months. The morbidity rates were 18% vs 7%, respectively, and the mortality rates were 2.5% vs 1.3%. The main sites of recurrent disease included the mesenterium, pelvic floor, diaphragm, and Glisson’s capsule. Women with recurrent disease treated with CRS + HIPEC + systemic chemotherapy had median survival rates of 26 months vs 16 months in the control group. The morbidity rates were 22% vs 15%, respectively, and the mortality rates were 3.3% vs 0%.Conclusion:Patients undergoing secondary debulking plus HIPEC for ovarian carcinoma relapse have a different prognosis when compared with patients with residual and recurrent disease. A different prognosis is presented in women undergoing secondary debulking plus HIPEC for ovarian carcinoma relapse when comparing patients with residual and recurrent disease.

Site of residual disease does not predict recurrence patterns in epithelial ovarian cancer patients undergoing primary debulking surgery

Objective: To examine the effect of residual disease volume on timing and pattern of recurrence among patients with advanced-stage epithelial ovarian/fallopian tube/primary peritoneal carcinoma after primary debulking surgery (PDS) and adjuvant chemotherapy.

A novel classification of residual disease after interval debulking surgery for advanced-stage ovarian cancer to better distinguish oncologic outcome

Complete surgical resection affords the best prognosis at the time of interval debulking surgery. When complete surgical resection is unachievable, optimal residual disease is considered the next best alternative. Despite contradicting evidence on the survival benefit of interval debulking surgery if macroscopic residual disease remains, the current definition of "optimal" in patients undergoing interval debulking surgery is defined as largest diameter of disease measuring ≤1.0 cm, independent of the total volume of disease. To examine the relationship between volume and anatomic distribution of residual disease and oncologic outcomes among patients with advanced-stage epithelial ovarian/fallopian tube/primary peritoneal carcinoma undergoing neoadjuvant chemotherapy then interval debulking surgery. For patients who did not undergo a complete surgical resection, a surrogate for volume of residual disease was used to assess oncologic outcomes. Patient demographics, operative characteristics, anatomic site of residual disease, and outcome data were collected from medical records of patients with International Federation of Gynecology and Obstetrics stage IIIC and IV epithelial ovarian cancer undergoing interval debulking surgery from January 2010 to July 2015. Among patients who did not undergo complete surgical resection but had ≤1 cm of residual disease, the number of anatomic sites (single location vs multiple locations) with residual disease was used as a surrogate for volume of residual disease. The effect of residual disease volume on progression-free survival and overall survival was evaluated. Of 270 patients undergoing interval debulking surgery, 173 (64.1%) had complete surgical resection, 34 (12.6%) had ≤1 cm of residual disease in a single anatomic location, 47 (17.4%) had ≤1 cm of residual disease in multiple anatomic locations, and 16 (5.9%) were suboptimally debulked. Median progression-free survival for each group was 14, 12, 10, and 6 months, respectively (P<.001). Median overall survival for each group was: 58, 37, 26, and 33 months, respectively (P<.001). Following interval debulking surgery, patients with complete surgical resection have the best prognosis, followed by patients with ≤1 cm single-anatomic location disease. In contrast, despite being considered "optimally debulked," patients with ≤1 cm multiple-anatomic location disease have a survival similar to suboptimally debulked patients.

Impact of Radicality Versus Timing of Surgery in Patients with Advanced Ovarian Cancer (Stage III C) Undergoing CRS and HIPEC-a Retrospective Study by INDEPSO.

HIPEC in addition to interval CRS has shown a survival benefit of 12months compared to CRS alone. However, there are many controversial issues pertaining to CRS itself which should be addressed first. To compare NACT and primary CRS approaches when CRS is categorized according to the extent of resection. To evaluate the feasibility of performing HIPEC at these two time points. A retrospective analysis of patients with stage III C ovarian cancer undergoing primary and interval CRS + HIPEC was performed. The surgical approach for interval CRS was classified as (1) resection of sites of residual disease alone or (2) resection of sites involved before NACT. The morphological response was divided into different categories, and surgeons had to state what they consider residual disease and what they do not. From January 2013 to December 2017, 54 patients were included (18-primary; 36-interval). Median PCI 11 vs 6.5 (p = 0.07); CC-0 was obtained in 77.7%. Three surgeons resected previously involved sites; three sites of residual disease only. All surgeons resected areas of scarring. Twenty percent patients had residual disease in "normal-looking" peritoneum. Morbidity (p = 0.09), median OS (p = 0.71), and median DFS (p = 0.54) were similar in the two groups. Early recurrence occurred in 50% with resection of residual disease alone compared to 16.6% when previous disease sites were resected (p = 0.07). Interval CRS should be performed to resect sites involved prior to NACT and not just sites of residual disease. HIPEC can be performed in both primary/interval settings with acceptable morbidity.

PC08.01 Debate #1: Locally Ablative Therapies Should Be Standard Treatment for Patients with NSCLC Oligometastese (PRO)

PC08.01 Debate #1: Locally Ablative Therapies Should Be Standard Treatment for Patients with NSCLC Oligometastese (PRO)