Initial Resection Research Articles

Hypofractionated re-irradiation with bevacizumab for relapsed chemorefractory glioblastoma after prior high dose radiotherapy: a feasible option for patients with large-volume relapse.

There remains no standard of care for patients with recurrent and chemorefractory glioblastoma. Re-irradiation (reRT) provides an additional management option. However, published series predominantly focus on small reRT volumes utilizing stereotactic hypofractionated regimens. Concerns regarding toxicity have limited utilisation of reRT for larger recurrences, however this may be mitigated with use of bevacizumab (BEV). A prospective database of patients managed with the EORTC-NCIC (Stupp) protocol 60Gy chemoradiotherapy protocol for glioblastoma between 2007 and 2021 was reviewed for those patients receiving reRT for chemorefractory relapse. Serial MRI and PET were used to establish true progression and exclude patients with pseudoprogression or radionecrosis from reRT. The primary endpoint was overall survival (OS) from date of reRT. Prognostic factors were also assessed. 447 patients managed for glioblastoma under the Stupp protocol were identified, of which 372 had relapsed and were thus eligible for reRT. 71 patients underwent reRT. Median relapse-free survival from diagnosis for the reRT and overall cohorts were similar at 11.6 months (95%CI:9.4-14.2) and 11.8 months (95%CI:9.4-14.2) respectively. 60/71 (85%) reRT patients had received BEV prior to reRT and continued concurrent BEV during reRT. Of the 11 patients not managed with BEV during reRT, 10 required subsequent salvage BEV. ReRT patients were younger (median 53 vs. 59 years, p < 0.001), had better performance status (86% vs. 69% ECOG 0-1, p = 0.002) and more commonly had MGMT promoter-methylated tumours (54% vs. 40%, p = 0.083) compared to non-reRT patients. Median reRT PTV volume was 135cm3 (IQR: 69-207cm3). Median OS from reRT to death was 7.1 months (95%CI:6.3-7.9). Patients aged < 50, 50-70 and > 70 years had post-reRT median OS of 7.7, 6.4 and 6.0 months respectively (p = 0.021). Median post-reRT survival was longer for patients with ECOG performance status 0-1 compared to 2-3 (8.1 vs. 6.3 months, p = 0.039). PTV volume, site of relapse, MGMT promoter-methylation status and extent of initial surgical resection were not associated with post-reRT survival. ReRT was well-tolerated. Out of the 6 patients (8%) admitted to hospital after reRT, only one was for reRT toxicity. This was a CTCAE grade 3 radiation necrosis event in a patient managed without prior BEV. Patients with recurrent glioblastoma who have been previously treated with 60Gy radiotherapy have a meaningful survival benefit from large volume re-irradiation which is well tolerated. ReRT should not be ignored as a salvage treatment option in patients with chemorefractory progressive disease.

Resection status and margin control in intraoperative frozen sectioning analysis of oral squamous cell carcinoma

PurposeIntraoperative frozen section analysis (IFSA) is a well-established procedure for determining the intraoperative soft tissue resection status in patients with oral squamous cell carcinoma (OSCC). Margin status is a major predictor of the patient´s outcome, histologically free margins of ≥ 5 mm are demanded. This study evaluates the accuracy of IFSA, the impact of margin status and the impact of intraoperative margin revision on disease-free survival (DFS) and overall survival (OS).MethodsThis retrospective study included 213 patients with OSCC. IFSA results were compared with definitive histopathological reports, Kaplan–Meier analysis was performed. Cut-off values were calculated for resection margins considering known risk factors.ResultsIFSA showed positive margins in 8 cases (3.8%). Kaplan–Meier analysis revealed no significant differences for OS or DFS if R0-status was achieved by initial resection or immediate re-resection.Final histopathological evaluation revealed false-positive IFSA in 3/8 cases (37.5%) and false-negative IFSA in 1/205 cases (0.5%). Sensitivity was 83.3% and specificity was 98.6%.Analysis of optimal cut-off values showed no general need for larger resection margins in patients with risk factors. Cut-off values were slightly higher for patients with the risk factor alcohol consumption (7 mm for OS and DFS) or pN + ECS- disease (7 mm for DFS). Optimal cut-off values for tumour-margin-distance were around 6 mm.ConclusionIFSA provides a valuable assessment method for intraoperative soft tissue resection margins. Risk factors seemingly do not significantly influence the extent of tumour resection.

Management of recurrent giant hemangiopericytoma: illustrative cases.

Hemangiopericytoma (HPC) is a rare malignancy accounting for 0.4% of intracranial tumors. HPCs are characterized by local aggressiveness, high rates of recurrence, and a tendency to metastasize to extracranial sites. These features make management of HPCs challenging, often requiring a combination of radical resection and radiation. Given their rarity, optimal treatment algorithms remain undefined. The authors report a series of four patients who underwent resection of intracranial HPC. Mean age at presentation was 49.3 years. Three patients had reoperation for progression of residual tumor, and one patient was surgically retreated for recurrence. One patient received adjuvant radiotherapy following initial resection, and three patients received adjuvant radiotherapy following resection of recurrent or residual disease. There was one death in the series. Average progression-free survival and overall survival following the index procedure were 32.8 and 82 months, respectively. Progression occurred locally in all patients, with metastatic recurrence in one patient. The current gold-standard treatment for intracranial HPC consists of gross-total resection followed by radiation therapy. This approach allows satisfactory local control; however, given the tendency for these tumors to recur either locally or distally within or outside of the central nervous system, there is a need for salvage therapies to improve long-term outcomes for patients.

Lower Geriatric Nutritional Risk Index and Prognostic Nutritional Index Predict Postoperative Prognosis in Patients with Hepatocellular Carcinoma.

Increasing evidence suggests that nutritional indices, including the geriatric nutritional risk index (GNRI) and prognostic nutritional index (PNI), are predictors of poor prognosis in patients with hepatocellular carcinoma (HCC). Hence, this study aimed to explore the value of the GNRI and PNI in evaluating postoperative prognosis in patients with HCC, particularly regarding its recurrence patterns. We performed a retrospective analysis of 203 patients with HCC who underwent initial hepatic resection. Patients were divided into two groups according to the GNRI (cutoff: 98) and PNI (cutoff: 45). The GNRI and PNI were significantly associated with body composition (body mass index and skeletal muscle mass index), hepatic function (Child-Pugh Score), tumor factors (tumor size and microvascular invasion), and perioperative factors (blood loss and postoperative hospitalization). Patients with a low PNI or low GNRI had significantly worse overall survival (OS) and recurrence-free survival. Patients with early recurrence had lower PNI and GNRI scores than those without early recurrence. Patients with extrahepatic recurrence had lower PNI and GNRI scores than those without extrahepatic recurrence. The PNI and GNRI might be useful in predicting the prognosis and recurrence patterns of patients with HCC after hepatic resection.

Recurrent Intrahepatic Cholangiocarcinoma: A 10-Point Score to Predict Post-Recurrence Survival and Guide Treatment of Recurrence.

Although up to 50-70% of patients with intrahepatic cholangiocarcinoma (ICC) recur following resection, data to predict post-recurrence survival (PRS) and guide treatment of recurrence are limited. Patients who underwent resection of ICC between 2000 and 2020 were identified from an international, multi-institutional database. Data on primary disease as well as laboratory and radiologic data on recurrent disease were collected. Factors associated with PRS were examined and a novel scoring system to predict PRS (PRS score) was developed and internallyvalidated. Among 986 individuals who underwent resection for ICC, 588 (59.6%) patients developed recurrence at a median follow up of 20.3months. Among patients who experienced a recurrence, 97 (16.5%) underwent re-resection/ablation for recurrent ICC; 88 (15.0%) and 403 (68.5%) patients received intra-arterial treatment or systemic chemotherapy/supportive therapy, respectively. Patient American Society of Anesthesiologists (ASA) class > 2 (1 point), primary tumor N1/Nx status (1 point), primary R1 resection margin (1 point), primary tumor G3/G4 grade(1 point), carbohydrate antigen (CA) 19-9 > 37 UI/mL (2 points) at recurrenceand carcinoembryonic antigen (CEA) > 5ng/mL (2 points) at recurrence, as well as recurrent bilateral disease (1 point) and early recurrence (1 point) were included in thePRS score. The PRS score successfully stratified patients relative to PRS and demonstrated strong discriminatory ability (C-index 0.70, 95% confidence interval 0.68-0.72). While a PRS score of 0-3 was associated with a 3-year PRS of 62.5% following resection/ablation for recurrent ICC, a PRS score > 3 was associated with a low 3-year PRS of 35.5% (p = 0.03). The PRS score demonstrated strong discriminatory ability to predict PRS among patients who had developed recurrencefollowing initial resection of ICC. The PRS score may be a useful tool to guide treatment among patients with recurrent ICC.

Abstract 2575: GD2 targeted dual-labeled intraoperative molecular imaging probe for neuroblastoma

Abstract Neuroblastoma (NB) is the most common pediatric extracranial solid tumor, with a 5-year survival rate under 50% for those with high-risk disease. Complete surgical resection is essential for these patients and is associated with improved outcomes. However, NB resection presents significant technical challenges due to encasement of vital structures that must be preserved, as well as remote deposits of disease. The current approach to find and safely resect tumor depends on the surgeon’s eyes and hands alone. Fluorescence tracers allow enhanced tumor visualization, but most are not molecularly targeted which leads to poor tumor to background signal. Further, fluorescent signal does not penetrate more than a few millimeters, a limitation that can be overcome by inclusion of a radiotracer. We, therefore, generated and evaluated a dual radio and fluorescent antibody-based probe targeting the GD2 tumor antigen to improve the identification of NB with widely available intraoperative handheld instruments. We generated an intraoperative probe (111In-αGD2-IRDye800CW) with retained affinity and stability. In vivo- Nu/j mice were injected with SK-N-BE(2) NB cells. After tumors grew for five weeks, mice were given tail vein injections of the probe. Gamma and optical biodistribution studies were performed to determine the specificity of binding and tumor to background signal four- and six-days post probe injection. Probe uptake was compared to an isotype. Gross dissections and surgeries aimed at improving completeness of resection were performed using a handheld fluorescent camera (SPY-PHI) and a gamma probe (Neoprobe). The handheld gamma probe detected xenografts with great sensitivity (average in vivo 818 cps of In111 in tumor region versus 34.8 cps in the tail). The fluorescent imaging showed high specific binding to the tumor region. Gamma biodistribution results indicated high accumulation within tumor (13.5 %ID/g) with lower accumulation in blood (3.49 %ID/g) and muscle (0.45 %ID/g). Uptake of the probe greatly exceeded isotype control antibody on days 4 and 6 post-agent injection, for both gamma and optical biodistributions. Initial tumor resection using 111In-DTPA-aGD2-IRDye800CW in an NB bearing mouse identified residual disease left behind when resection was performed using white light alone; the residual disease was then removed, guided by fluorescence imaging. Our dual-labeled probe demonstrated antigen specificity and allowed for the sensitive detection and visualization of NB in vivo with widely available intraoperative tools. This targeted probe could provide a means to improve surgical NB resection, by enabling localization of the all regions of tumor using radio-guidance, followed by clear definition of tumor margins with fluorescent signal, to maximize preservation of vital tissues. Ultimately, we believe this approach can improve safety, extent of NB resection, and patient outcomes. Citation Format: ReidAnn E. Sever, Lauren Taylor Rosenblum, Kayla C. Stanley, Dominic M. Menendez, W Barry Edwards, Marcus M. Malek, Gary Kohanbash. GD2 targeted dual-labeled intraoperative molecular imaging probe for neuroblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2575.

Initial local resection versus early referral for spermatic cord sarcoma: Any impact on treatment timelines and oncological outcomes?

ObjectivesSpermatic cord sarcomas are exceedingly rare, often misdiagnosed and subsequently improperly treated at local hospitals. This retrospective study looked at the oncological outcomes of spermatic cord sarcoma cases managed with curative intent resection at a tertiary referral sarcoma centre. We specifically studied how initial inadequate resections impact the oncologic outcomes compared to primary tumour resections at the reference centre. MethodsOne hundred eighteen consecutive patients affected by primary, localized spermatic cord sarcoma surgically managed at our reference centre from January 2001 through January 2021 were included. Primary endpoints were local relapse free (LRFS), distant metastasis free (DMFS) and overall survival (OS). These outcomes were evaluated with multi-nomial logistic regression and Cox proportional hazards regression models for a co-relation to known patient, tumour and treatment-related prognostic factors, including a prior inadequate resection and time from diagnosis to a complete oncologic resection as independent variables. Secondarily, we compared the above variables and treatment intervals among the subgroups of primary versus re-resection surgery. ResultsOver a median follow-up of 54 months (IQR 25–105), 12 patients (10.2%) developed local recurrence (LR) and 14 (11.6%) had distant metastasis (DM). 5-year local relapse (LRFS) and distant metastasis-free survival (DMFS) were 89.3% and 86.5%, respectively. Higher tumour grade and size were associated with a worse DMFS (p=<0.05). Likewise, marginal (R1) resection correlated with an inferior LRFS (p=< 0.05).Eighty-four patients (71.2%) had their initial diagnosis established on an inadequate surgical excision performed in a local hospital, followed by a re-excision at our centre (Re-resection group). During the same period, 34 (28.8%) were managed primarily with biopsy and treatment at our reference centre (Primary-resection group). The two groups had statistically significant differences in tumour size, histopathology, surgery duration, rate of postoperative complication and R0 resection (p < 0.005). Additionally, the difference in time intervals to achieve the treatment targets was statistically insignificant and did not correlate to the risk of recurrence as an independent variable. Residual disease was present in 51.2 % (n = 43) of the re-excision specimens. However, following a complete R0 resection, this did not correlate with a higher risk of recurrence (p = 0.481). ConclusionPrompt referral to a tertiary centre, where multidisciplinary evaluation and sound oncologic resections are the standard of treatment, can align the OS and DFS of patients receiving incomplete surgery elsewhere to those treated primarily in referral centres. The primary determinant of prognosis remains surgical margin, tumour size and grade.

Hospital variation and outcomes after repeat hepatic resection for colorectal liver metastases: a nationwide cohort study

BackgroundApproximately 70% of patients with colorectal liver metastases (CRLM) experiences intrahepatic recurrence after initial liver resection. This study assessed outcomes and hospital variation in repeat liver resections (R-LR). MethodsThis population-based study included all patients who underwent liver resection for CRLM between 2014 and 2022 in the Netherlands. Overall survival (OS) was collected for patients operated on between 2014 and 2018 by linkage to the insurance database. ResultsData of 7479 liver resections (1391 (18.6%) repeat and 6088 (81.4%) primary) were analysed. Major morbidity and mortality were not different. Factors associated with major morbidity included ASA 3+, major liver resection, extrahepatic disease, and open surgery. Five-year OS after repeat versus primary liver resection was 42.3% versus 44.8%, P = 0.37. Factors associated with worse OS included largest CRLM >5 cm (aHR 1.58, 95% CI: 1.07–2.34, P = 0.023), >3 CRLM (aHR 1.33, 95% CI: 1.00–1.75, P = 0.046), extrahepatic disease (aHR 1.60, 95% CI: 1.25–2.04, P = 0.001), positive tumour margins (aHR 1.42, 95% CI: 1.09–1.85, P = 0.009). Significant hospital variation in performance of R-LR was observed, median 18.9% (8.2% to 33.3%). ConclusionSignificant hospital variation was observed in performance of R-LR in the Netherlands reflecting different treatment decisions upon recurrence. On a population-based level R-LR leads to satisfactory survival.

Patterns of recurrence and disease progression in patients with positive-margin olfactory neuroblastoma following primary resection.

Olfactory neuroblastoma (ONB) is a rare, malignant tumor of the sinonasal tract that arises from olfactory epithelium. Although surgery is the preferred first-line treatment, tumor involvement of adjacent structures may preclude the ability to achieve negative margins during initial resection. Herein, the authors examine the oncological outcomes of patients with positive margins after primary resection of ONB, with the aim of determining predictors of disease progression and patterns of recurrence. The authors performed an institutional review of 25 patients with positive-margin ONB after resection. Cox survival analyses were used to determine any statistically significant predictors of worse progression-free survival (PFS) and overall survival (OS). A total of 93 patients who were diagnosed with ONB were identified, of whom 25 patients had positive margins following their primary resection. Eleven (44%) had a delayed finding of positive margins that were initially negative in the operating room but returned as positive on final pathology. Four patients had subtotal resection (STR), whereas the remaining patients underwent gross-total resection. Twenty-four patients received adjuvant radiotherapy (96%), and 15 additionally received adjuvant chemotherapy (60%). Fourteen patients (56%) experienced recurrence/progression at a median time of 35 months following resection (IQR 19-70 months). Local recurrence occurred in 10 patients (40%), regional in 9 (36%), and distant metastasis in 2 (8%). In Cox survival analyses, the 5-year PFS and OS were 55.1% and 79.2%, respectively. Kadish stage D was predictive of worse PFS in univariate (hazard ratio [HR] 15.67, 95% CI 3.38-72.61, p < 0.001) and multivariate (HR 15.46, 95% CI 1.45-164.91, p = 0.023) analyses. Hyams grade, adjuvant chemotherapy, and primary radiotherapy were not associated with PFS. Furthermore, Kadish stage D and STR were predictive of worse OS in univariate analysis (HR 12.64, 95% CI 2.03-78.86, p = 0.007; HR 7.31, 95% CI 1.45-36.84, p = 0.016; respectively). However, local and regional recurrence was not associated with worse OS. Approximately half of patients with positive-margin ONB may experience disease recurrence. Patients with an advanced disease stage (Kadish D) may have a higher likelihood of developing recurrence/progression. Furthermore, patients with tumor burden following resection (STR and Kadish D) may have worse OS. However, in positive-margin ONB with no gross disease following initial resection, the presence of disease recurrence does not significantly alter survival when receiving salvage therapy.

Multidisciplinary management of pleomorphic dermal sarcoma of the scalp: A single institution study

BackgroundPleomorphic dermal sarcoma (PDS) of the scalp is a rare cutaneous malignancy, the location of which creates unique technical and cosmetic obstacles. Optimal management is not defined. We reviewed our institution’s approach and outcomes for this entity. Materials & methodsBetween 2000–2020, 15 patients with scalp PDS were evaluated and treated at our multidisciplinary sarcoma center. Patient characteristics, treatment approach, and outcomes were analyzed. ResultsThirteen patients (87%) presented with primary disease alone, one (7%) presented with recurrent disease after initial resection, and one (7%) presented with synchronous primary and metastatic disease. Radiation therapy (RT) was recommended in 10 patients (67%) and completed in 8 (53%) (3 preoperative, 5 postoperative). Eight patients (53%) underwent staged plastic surgery complex wound closure. Thirteen patients were alive without disease, one was alive with disease, and one was deceased with known recurrent disease at time of last follow-up. ConclusionLimited data are available to guide management of scalp PDS. Due to possible need for staged plastic surgery closure to ensure negative margins and optimize wound healing, initiation of postoperative RT may be delayed. Future multi-institutional study is required to further define the extent of surgery and role and timing of RT.

Development of preoperative and postoperative models to predict recurrence in postoperative glioma patients: a longitudinal cohort study

BackgroundGlioma recurrence, subsequent to maximal safe resection, remains a pivotal challenge. This study aimed to identify key clinical predictors influencing recurrence and develop predictive models to enhance neurological diagnostics and therapeutic strategies.MethodsThis longitudinal cohort study with a substantial sample size (n = 2825) included patients with non-recurrent glioma who were pathologically diagnosed and had undergone initial surgical resection between 2010 and 2018. Logistic regression models and stratified Cox proportional hazards models were established with the top 15 clinical variables significantly influencing outcomes screened by the least absolute shrinkage and selection operator (LASSO) method. Preoperative and postoperative models predicting short-term (within 6 months) postoperative recurrence in glioma patients were developed to explore the risk factors associated with short- and long-term recurrence in glioma patients.ResultsPreoperative and postoperative logistic models predicting short-term recurrence had accuracies of 0.78 and 0.87, respectively. A range of biological and early symptomatic characteristics linked to short- and long-term recurrence have been pinpointed. Age, headache, muscle weakness, tumor location and Karnofsky score represented significant odd ratios (t > 2.65, p < 0.01) in the preoperative model, while age, WHO grade 4 and chemotherapy or radiotherapy treatments (t > 4.12, p < 0.0001) were most significant in the postoperative period. Postoperative predictive models specifically targeting the glioblastoma and IDH wildtype subgroups were also performed, with an AUC of 0.76 and 0.80, respectively. The 50 combinations of distinct risk factors accommodate diverse recurrence risks among glioma patients, and the nomograms visualizes the results for clinical practice. A stratified Cox model identified many prognostic factors for long-term recurrence, thereby facilitating the enhanced formulation of perioperative care plans for patients, and glioblastoma patients displayed a median progression-free survival (PFS) of only 11 months.ConclusionThe constructed preoperative and postoperative models reliably predicted short-term postoperative glioma recurrence in a substantial patient cohort. The combinations risk factors and nomograms enhance the operability of personalized therapeutic strategies and care regimens. Particular emphasis should be placed on patients with recurrence within six months post-surgery, and the corresponding treatment strategies require comprehensive clinical investigation.

Prediction of recurrence risk in patients with non-muscle-invasive bladder cancer

ObjectiveNon-muscle-invasive bladder cancer (NMIBC) remains a common challenge in uro-oncology with conflicting reports on recurrence risk. This study aimed to elucidate the recurrence rate of NMIBC in the Cancer Clinic of Shahid Beheshti Hospital in Iran and to investigate related parameters affecting recurrence risk. MethodsThe data of 143 patients with NMIBC, who underwent treatment between January 2017 and January 2020 and were followed up from the initial transurethral resection of bladder tumor until November 30, 2020 in our institution, were retrospectively assessed. The Cox regression analysis and Kaplan–Meier plot of recurrence-free survival were used to determine independent contributing factors for tumor recurrence. ResultsAmong patients with NMIBC, 83.9% were male, and 16.1% were female, with a mean age of 64.4 (standard deviation [SD] 12.9) years. During the follow-up, 71 (49.7%) patients showed tumor recurrence, with a mean recurrence time of 11.5 (SD 6.9) months. In the Chi-square test or Fisher's exact test, the age (≥65 years) (p=0.037), obesity (body mass index ≥30 kg/m2) (p=0.004), no diabetes mellitus (p=0.005), smoking (current or former smoker) (p=0.001), immediate perfusion therapy (p=0.035), number of tumors (>3) (p<0.001), and tumor stage (Ta, T1, and Tis) (p=0.001) had independent significant effects on the recurrence of NMIBC. The multivariate Cox regression analysis indicated that preoperative obesity (hazards ratio [HR] 7.90; 95% confidential interval [CI] 4.01–15.55; p<0.001), current or former smoking (HR 1.85; 95% CI 1.07–3.20; p=0.027), and a high-grade tumor (HR 4.03; 95% CI 1.59–10.25; p=0.003) were significant predictors of tumor recurrence. The Kaplan–Meier plot of recurrence-free survival showed that obesity (log-rank p<0.001), current or former smoking (log-rank p=0.001), and a high-grade tumor (log-rank p=0.006) were associated with a shorter time interval until the first tumor recurrence. ConclusionThe study found a high recurrence rate of NMIBC in Iran from January 2017 to January 2020, with the obesity, smoking history, and the high-grade tumor as contributing factors.

Adjuvant Stereotactic Radiosurgery for Clear Cell Meningiomas

ObjectiveClear cell meningiomas (CCM) are an uncommon meningioma subtype marked by aggressive growth and high rates of recurrence despite initial resection. The present study evaluates the adjuvant benefit of stereotactic radiosurgery (SRS) for residual or recurrent tumors. MethodsAfter review of our prospectively maintained data base, we identified 6 patients (3 female) with histologically confirmed Grade 2 CCMs. The median age of the patients at the time of SRS was 45 years. Five patients had undergone prior gross total surgical resection and 1 patient had subtotal resection before SRS. The median SRS treatment volume was 4.7 cc and the median radiosurgical margin dose was 13 Gy (range: 10 – 15 Gy). ResultsThe median follow-up time was 35.5 months (range 6 – 168 months). Three patients achieved tumor control after the first SRS procedure. Three patients experienced tumor progression at 4, 22, and 32 months after initial SRS. Tumor control was obtained in 2 of these patients after additional SRS. One patient with multiple SRS procedures had suspected adverse radiation effect that was successfully treated with corticosteroids followed by bevacizumab. ConclusionsTumor control was maintained in 5 of 6 patients after one or more SRS procedures. SRS should be considered for early intervention after surgical resection of CCM. To maximize the tumor control rate, patients with diagnosed CCM should be treated more generously and higher margin dose should be prescribed. Patients with CCM should be counselled that more than one SRS may be necessary to provide sustained tumor control.

Pulmonary Metastasectomy for Adrenocortical Carcinoma-Not If, but When.

Adrenocortical carcinoma (ACC) commonly metastasizes to the lungs, and pulmonary metastasectomy (PM) is utilized due to limited systemic options. All ACC patients with initially only lung metastases (LM) from a single institution constituted this observational case series. Kaplan-Meier and Cox proportional hazard analyses evaluated the association with potential prognostic factors and outcomes. Overall survival (OS) was calculated from the date of the PM or, in those patients who did not undergo surgery, from the development of LM. A total of 75 ACC patients over a 45-year period met the criteria; 52 underwent PM, and 23 did not. The patients undergoing PM had a median OS of 3.1 years (95% CI: 2.4, 4.7 years) with the 5- and 10-year OS being 35.5% and 32.8%, respectively. The total resected LM did not impact the OS nor the DFS. The patients who developed LM after 11 months from the initial ACC resection had an improved OS (4.2 years; 95% CI: 3.2, NR; p = 0.0096) compared to those developing metastases earlier (2.4 years; 95% CI: 1.6, 2.8). Patients who underwent PM within 11 months of adrenalectomy demonstrated a reduced OS (2.2 years; 95% CI: 1.0, 2.7) compared to those after 11 months (3.6 years, 95% CI: 2.6, NR; p = 0.0045). PM may provide benefit to those patients with LM at presentation (HR: 0.5; p = 0.2827), with the time to first PM as a time-varying covariate. PM appears to have a role in ACC patients. The number of nodules should not be an exclusion factor. Patients developing LM within a year of primary tumor resection may benefit from waiting before further surgeries, which may provide additional insight into who may benefit from PM.

Desmoid Tumours: Experience of the Medical Oncology Department of Pierre and Marie Curie Center Algiers

Introduction Desmoid tumours, also known as aggressive deep fibromatoses, are soft tissue tumours. Histologically benign, they are characterised by a slow infiltrative course with a high rate of local recurrence. Patients and methods: We report a retrospective series of 10 patients treated in the medical oncology department of the Pierre &amp; Marie Curie Centre over a period of 4 years. 6 were women and 4 men, with a sex ratio of 1.5 in favour of women. The average age was 36 [23-53]. 20% (n=2) of patients had familial adenomatous polyposis. 90% of patients had an extra-abdominal desmoid tumour compared with only 10% in the abdominal wall. 50% of patients underwent initial resection, 60% of whom recurred after 1 year. Only one patient underwent additional radiotherapy. Initial surveillance was proposed in 50% of patients. 60% progressed after 2 years. Only one patient underwent surgical treatment combined with radiotherapy after an initial monitoring period of 9 years. Treatment with IMATINIB 400mg/d was initiated in 60% (n=6) of patients after progression or local recurrence. One patient received tamoxifen for one year. Results: Lesion stability was observed in 6 patients (60%), a partial response (left scapular) in 1 patient and local progression in 1 patient. Tolerability: Grade 3 neutropenia in 1 patient and Grade 2 liver toxicity. Conclusion : Desmoid tumours are rare tumours which progress slowly and are locally aggressive. Their prognosis is closely linked to their recurrence. The current therapeutic approach advocates a "WAIT AND SEE" strategy, particularly in asymptomatic, non-progressive forms. Surgery is only indicated if the immediate vital or functional prognosis is at risk.

Surgical-decision making in the setting of unsuspected N2 disease: a cost-effectiveness analysis.

Identification of unsuspected nodal metastasis may occur at the time of operation for a stage I non-small cell lung cancer. Guidelines for this scenario are unclear. Our goal was to assess the cost-effectiveness of aborting the operation in an attempt to first provide neoadjuvant systemic therapy compared with upfront resection. A computer simulation Markov model with a lifetime horizon was constructed to compare the costs and clinical outcomes, as measured by quality-adjusted life-years (QALYs), of upfront resection at the time of identification of unsuspected N2 mediastinal disease vs. aborting initial resection and continuing with neoadjuvant therapy prior to resection. Input parameters for the model were derived from published literature with costs measured from the healthcare perspective. The incremental cost-effectiveness ratio (ICER) was evaluated with a willingness-to-pay (WTP) threshold of $150,000/QALY. Both deterministic (one-, two-, and three-way) and probabilistic sensitivity analysis (PSA) were performed to assess the impact of variation in input parameter values on model results. Aborting initial resection in favor of neoadjuvant therapy resulted in both higher costs ($40,415 vs. $29,873) and more QALYs (3.95 vs. 2.84) relative to upfront resection, yielding an ICER of $9,526/QALY. While variation in overall survival had a significant impact on the ICER, perioperative variables did not. As the annual mortality of best-case therapy in the abort group increased from a base-case estimate of 11% to 15%, the ICER exceeded the WTP threshold of $150,000/QALY. Subsequent one- and two-way sensitivity analyses did not find substantially alter the overall results. PSA resulted in aborting resection to be cost-effective in 99.7% of samples, with 13% of samples dominating upfront resection. Treatment of stage IIIa lung cancer requires the input of a multidisciplinary team who must consider cost, quality of life, and overall survival. As new treatments are developed, further analyses should be performed to determine optimal therapy.

Outcomes and complications of postoperative seroma cavities following soft-tissue sarcoma resection.

Seroma development is a known complication following extremity and trunk soft-tissue sarcoma (STS) resection. The purpose of this study is to evaluate and characterize seroma outcomes and the development of associated complications. A retrospective review of 123 patients who developed postoperative seromas following STS resection at a single institution was performed. Various patient and surgical factors were analyzed to determine their effect on overall seroma outcomes. 77/123 seromas (62.6%) were uncomplicated, 30/123 (24.4%) developed infection, and 16/123 (13.0%) were symptomatic and required aspiration or drainage for symptom relief at an average of 12.2 months postoperatively. 65/123 (52.8%) seromas resolved spontaneously at an average time of 12.41 months. Seromas in the lower extremity (p=0.028), surgical resection volume >864 cm3, (p=<0.001) and initial seroma volume >42 cm3 (p=<0.001) increased the likelihood of infection. 90% of infected seromas developed the infection within the first three months following initial resection. No seromas which were aspirated or drained ultimately developed an infection following these procedures, though 50% recurred. Most seromas following STS resection are uncomplicated and do not require intervention, though a large resection cavity >864 cm3 and a large seroma volume >42 cm3 are risk factors for complications.

Second look, in primary site recurrence or second primary for T1 and T2 glottic cancer treated by CO2 laser

Background: Aim was to analyze the impact of second-look surgery in the surveillance of T1 and T2 glottic cancer treated with CO2 laser. Methods: Retrospective review of 98 patients treated between February 2005 and December 2022. Results: Among 98 patients with early glottic cancer (T1/T2), 56 (57%) with suspected recurrence underwent a second-look surgery. Of all patients, 38 (38.77%) recurred 6 months after initial resection, 17 of which (45%) had a lesion in a different site from the primary. Of these 38 patients, 22 (58%) underwent laser surgery once, 12 (32%) underwent laser surgery twice, and 4 (10%) underwent laser surgery on three occasions during follow-up. The 5-year disease-free survival, 5-year survival, and larynx preservation rates were, respectively, 54%, 82%, and 90.8%. Conclusions: Transoral resection is currently the first treatment option for early-stage glottic carcinoma because diagnosis and prompt treatment can be provided on an outpatient basis at the same time.

Randomized phase II study comparing neoadjuvant FLOT versus DOS for patients with type 4 or large type 3 gastric cancer (JCOG2204).

TPS418 Background: A randomized phase III trial (JCOG0501) failed to demonstrate a survival advantage of neoadjuvant chemotherapy with S-1 plus cisplatin (SP) for patients with resectable macroscopic type 4 and large type 3 gastric cancer (GC). Currently, initial resection followed by adjuvant chemotherapy is performed as the standard treatment for this population as well as general type GC in Japan. However, macroscopic type 4 and large type 3, mostly overlapping with scirrhous or linitis plastica type, have distinctive natures in age, dominant histology and metastatic site, exhibiting unfavorable prognosis after surgery with curative intent. Further therapeutic development using peri-operative chemotherapy is urgently desired for the improvement of this hard-to-treat subset of GC. Based on the successful results of the FLOT4 trial and PRODIGY trial, FLOT (5-fluorouracil/leucovorin/oxaliplatin/docetaxel) and DOS (docetaxel/oxaliplatin/S-1) will be anticipated to offer more potent efficacy compared to platinum doublet. However, it remains unclear which of these two regimens should be selected as a test arm of future phase III confirming efficacy of neoadjuvant chemotherapy in Japan. Methods: JCOG2204 is a multi-center, randomized phase II trial comparing neoadjuvant chemotherapy with FLOT (5-fluorouracil/levofolinate/oxaliplatin/docetaxel) versus DOS for resectable type 4 and large type 3 GC. This trial adopted the selection design to determine the most promising regimen for the subsequent phase III trial. Patients with histologically confirmed adenocarcinoma of the stomach, presenting with macroscopic type 4 or larger lesions (≥8 cm) of type 3, are eligible for this trial. Prior to registration, it is required to confirm the absence of non-curable factors other than positive lavage cytology (CY1) or peritoneal dissemination localized around the stomach (P1a) in a staging laparoscopy. Neoadjuvant FLOT arm consist of 4 courses of oxaliplatin (85 mg/m2) and docetaxel (50 mg/m²) with levofolinate (200 mg/m2) IV infusion for 1-2 hours, then 5-FU (2600 mg/m2, civ) for 24 hours on day 1, biweekly. Neoadjuvant DOS arm consists of 3 courses of oxaliplatin (100 mg/m2) and docetaxel (40 mg/m2) IV infusion for 1-2 hours on day 1, followed by oral S-1 80–120 mg/m2/day for 2 weeks (days 1–14), in a 3-week cycle. Adjuvant chemotherapy is performed according to the pathological TNM stage. A sample size was calculated based on Simon’s selection design assuming that a proportion of patients achieving pathological response Grade 1b or higher will be 65% in the superior regimen, 10% higher than 55% in the other. A total of 76 patients, which are required to ensure at least an 80% probability of correct selection, are planned to be enrolled over 2 years. Enrollment in JCOG2204 begun on 14th July, 2023 and clinical trial information is available in Japan Registry of Clinical Trials (jRCTs031230231). Clinical trial information: jRCTs031230231 .

Impact of the COVID-19 pandemic on colorectal cancer stage at presentation.

80 Background: The primary study objective was to assess the impact of COVID-19 on the stage at presentation for patients with newly diagnosed colorectal cancer treated within a large cancer center network. Additionally, we aimed to evaluate differences in pathologic stage and treatment modality for patients diagnosed with colorectal cancer both immediately before and during the height of the COVID-19 pandemic. Methods: A retrospective analysis was performed on all subjects newly diagnosed with colorectal cancer between January 2019 and April 2021 at Levine Cancer Institute. Patients had a primary diagnosis of adenocarcinoma of the colon, rectum, or appendix. Patients were categorized into two cohorts based on date of diagnosis, with the pre-COVID-19 group diagnosed between January 2019 and February 2020 and the COVID-19 group diagnosed between March 2020 and April 2021. Chi-squared tests were used to evaluate the association between COVID-19 group and stage at presentation as well as pathologic stage. Results: A total of 1,190 patients were diagnosed with colorectal cancer within the study timeframe. Of the 613 patients diagnosed pre-COVID-19, 159 (25.9%) had metastatic disease at initial presentation. Comparatively, 577 patients were diagnosed during the COVID-19 study period, with 143 (24.8%) presenting with metastatic disease (p = 0.65).Of the 888 patients who presented with non-metastatic disease, 770 underwent primary surgical intervention for the initial treatment of their cancer, with 396 (87.2%) pre-COVID-19 and 374 (86.2%) COVID-19 patients receiving surgery (p = 0.65). Likewise, no significant difference was observed for T-classification, N-classification, or overall pathologic stage among patients undergoing surgical resection between the pre-COVID-19 and COVID-19 groups (p = 0.20; Table). Furthermore, amongst patients who presented with non-metastatic disease, chemotherapy was utilized for 200 (44.1%) patients diagnosed pre-COVID-19 and 190 (43.8%) patients diagnosed during COVID-19 (p = 0.93). Conclusions: We did not observe a significant difference in the proportion of patients presenting with metastatic colorectal cancer during COVID-19 versus those presenting pre-COVID-19. Furthermore, there was no significant difference observed among non-metastatic patients between the two groups for rates of initial surgical resection, pathologic stage, and treatment with chemotherapy. [Table: see text]