Extended-duration antibiotics are not associated with a reduction in surgical site infection in patients with ovarian cancer undergoing cytoreductive surgery with large bowel resection.

OBJECTIVE(S): To evaluate whether extended dosing of antibiotics (ABX) after cytoreductive surgery (CRS) with large bowel resection for advanced ovarian cancer is associated with reduced incidence of surgical site infection (SSI) compared to standard intra-operative dosing and evaluate predictors of SSI. METHODS: A retrospective single-institution cohort study was performed in patients with stage III/IV ovarian cancer who underwent CRS from 2009 to 2017. Patients were divided into two cohorts: 1) standard intra-operative dosing ABX and 2) extended post-operative ABX. All ABX dosing was at the surgeon's discretion. The impact of antibiotic duration on SSI and other postoperative outcomes was assessed using univariate and multivariable Cox regression models. RESULTS: In total, 277 patients underwent cytoreductive surgery (CRS) with large bowel resection between 2009 and 2017. Forty-nine percent (n = 137) received standard intra-operative ABX and 50.5% (n = 140) received extended post-operative ABX. Rectosigmoid resection was the most common large bowel resection in the standard ABX (89.9%, n = 124) and extended ABX groups (90.0%, n = 126), respectively. No significant differences existed between age, BMI, hereditary predisposition, or medical comorbidities (p > 0.05). No difference was appreciated in the development of superficial incisional SSI between the standard ABX and extended ABX cohorts (10.9% vs. 12.9%, p = 0.62). Of patients who underwent a transverse colectomy, a larger percentage of patients developed a superficial SSI versus no SSI (21% vs. 6%, p = 0.004). CONCLUSION(S): In this retrospective study of patients with advanced ovarian cancer undergoing CRS with LBR, extended post-operative ABX was not associated with reduced SSI, and prolonged administration of antibiotics should be avoided unless clinically indicated.

Proton versus photon adjuvant radiotherapy: a multicenter comparative evaluation of recurrence following spinal chordoma resection.

OBJECTIVE: Chordomas are rare tumors of the skull base and spine believed to arise from the vestiges of the embryonic notochord. These tumors are locally aggressive and frequently recur following resection and adjuvant radiotherapy. Proton therapy has been introduced as a tissue-sparing option because of the higher level of precision that proton-beam techniques offer compared with traditional photon radiotherapy. This study aimed to compare recurrence in patients with chordomas receiving proton versus photon radiotherapy following resection by applying tree-based machine learning models. METHODS: The clinical records of all patients treated with resection followed by adjuvant proton or photon radiotherapy for chordoma at Mayo Clinic were reviewed. Patient demographics, type of surgery and radiotherapy, tumor recurrence, and other variables were extracted. Decision tree classifiers were trained and tested to predict long-term recurrence based on unseen data using an 80/20 split. RESULTS: Fifty-three patients with a mean ± SD age of 55.2 ± 13.4 years receiving surgery and adjuvant proton or photon therapy to treat chordoma were identified; most patients were male. Gross-total resection was achieved in 54.7% of cases. Proton therapy was the most common adjuvant radiotherapy (84.9%), followed by conventional or external-beam radiation therapy (9.4%) and stereotactic radiosurgery (5.7%). Patients receiving proton therapy exhibited a 40% likelihood of having recurrence, significantly lower than the 88% likelihood observed in those treated with nonproton therapy. This was confirmed on logistic regression analysis adjusted for extent of tumor resection and tumor location, which revealed that proton adjuvant radiotherapy was associated with a decreased risk of recurrence (OR 0.1, 95% CI 0.01-0.71; p = 0.047) compared with photon therapy. The decision tree algorithm predicted recurrence with an accuracy of 90% (95% CI 55.5%-99.8%), with the lowest risk of recurrence observed in patients receiving gross-total resection with adjuvant proton therapy (23%). CONCLUSIONS: Following resection, adjuvant proton therapy was associated with a lower risk of chordoma recurrence compared with photon therapy. The described machine learning models were able to predict tumor progression based on the extent of tumor resection and adjuvant radiotherapy modality used.

Assessment of minimum target dose as a predictor of local failure after spine SBRT.

OBJECTIVES: Metastasis-directed stereotactic body radiation therapy (SBRT) has demonstrated robust clinical benefits in carefully selected patients, improving local control and even overall survival (OS). We assess a large database to determine clinical and dosimetric predictors of local failure after spine SBRT. METHODS: Spine SBRT treatments with imaging follow-up were identified. Patients were treated with a simultaneous integrated boost technique using 1 or 3 fractions, delivering 20-24 Gy in 1 fraction to the gross tumor volume (GTV) and 16 Gy to the low dose volume (or 27-36 Gy and 21-24 Gy for 3 fraction treatments). Exclusions included: lack of imaging follow-up, proton therapy, and benign primary histologies. RESULTS: 522 eligible spine SBRT treatments (68 % single fraction) were identified in 377 unique patients. Patients had a median OS of 43.7 months (95 % confidence interval: 34.3-54.4). The cumulative incidence of local failure was 10.5 % (7.4-13.4) at 1 year and 16.3 % (12.6-19.9) at 2 years. Local control was maximized at 15.3 Gy minimum dose for single-fraction treatment (HR = 0.31, 95 % CI: 0.17 - 0.56, p < 0.0001) and confirmed via multivariable analyses. Cumulative incidence of local failure was 6.1 % (2.6-9.4) vs. 14.2 % (8.3-19.8) at 1 year using this cut-off, with comparable findings for minimum 14 Gy. Additionally, epidural and soft tissue involvement were predictive of local failure (HR = 1.77 and 2.30). CONCLUSIONS: Spine SBRT offers favorable local control; however, minimum dose to the GTV has a strong association with local control. Achieving GTV minimum dose of 14-15.3 Gy with single fraction SBRT is recommended whenever possible.

Carboplatin, paclitaxel, and pembrolizumab followed by pembrolizumab maintenance for primary treatment of incompletely resected epithelial ovarian cancer.

Objective: Incompletely resected epithelial ovarian cancer represents a poor prognostic subset of patients. Novel treatment strategies are needed to improve outcomes for this population. We evaluated a treatment strategy combining platinum-based chemotherapy with pembrolizumab followed by pembrolizumab maintenance therapy in the first-line treatment after incomplete resection of epithelial ovarian cancer patients. Methods: This was a single-arm, non-randomized pilot study of carboplatin, taxane, and immune checkpoint inhibitor, pembrolizumab, followed by 12 months of maintenance pembrolizumab in patients with incompletely resected epithelial ovarian cancer (EOC). Results: A total of 29 patients were enrolled and evaluated for efficacy and safety. The best response to therapy was complete response in 16 (55%) patients, partial response in 9 (31%) patients, and 3 (10%) patients with progression of disease. The median progression-free survival (PFS) was 13.2 months. Grade 3 and 4 toxicities occurred in 20% of patients. In all, 7 patients discontinued therapy due to adverse events. Quality-of-life scores remained high during therapy. Response to therapy did not correlate with PD-L1 tumor expression. Conclusions: Combination platinum-taxane therapy with pembrolizumab did not increase median progression-free survival in this cohort of patients. Key message: EOC is an immunogenic disease, but immune checkpoint inhibitor therapy has yet to impact outcomes. The current study utilized pembrolizumab in combination with standard chemotherapy followed by a maintenance treatment strategy in incompletely resected EOC. Progression-free survival was not extended in this poor prognostic group with combined chemotherapy and immunotherapy. Clinical trial registration: https://clinicaltrials.gov/, identifier NCT 027766582.

Laparoscopic predictability of minimally invasive interval debulking in advanced ovarian cancer: The MIID-SOC trial.

BACKGROUND: We sought to create a laparoscopic-based model to predict the ability to perform a minimally invasive (MIS) cytoreductive surgery in advanced epithelial ovarian cancer patients who have received neoadjuvant chemotherapy (NACT). METHODS: Fifty women were enrolled in a multi-institutional prospective pilot study (NCT03378128). Each patient underwent laparoscopic evaluation of 43 abdominopelvic sites followed by surgeon dictated surgical approach, either continue MIS or laparotomically. However, if the procedure continued MIS, the placement of a hand-assist port for manual palpation was mandated to emulate a laparotomic approach and all 43 sites were re-evaluated. Sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy were calculated for each site to predict MIS resectability. Each parameter was assigned a numeric value based on the strength of statistical association and a total predictive index score (PIV) was assigned for each patient. Receiver operating characteristic curve analysis was used to assess the ability of the model to predict the MIS approach. RESULTS: Twenty-seven patients (61%) underwent MIS surgery. The following abdominopelvic sites were selected for inclusion in the model: gastrosplenic ligament, rectum, left mesocolon, transverse colon, right colon, cecum, appendix, liver capsule, intrahepatic fossa/gallbladder, ileum/jejunum. Using the PIV, a ROC was generated with an AUC = 0.695. In the final model, a PIV <2 identified patients able to undergo an optimal MIS cytoreductive surgery with an accuracy of 68.2%. The specificity, or the ability to identify patients who would not be able to undergo an optimal MIS interval cytoreductive surgery, was 66.7%. CONCLUSION: This predictive index model may help to guide future inclusion criteria in randomized studies evaluating the MIS approach in advanced epithelial ovarian cancer.

Salivary iodide status as a measure of whole body iodine homoeostasis?

Iodine is a trace element required to produce the thyroid hormones, which are critical for development, growth and metabolism. To ensure appropriate population iodine nutrition, convenient and accurate methods of monitoring are necessary. Current methods for determining iodine status either involve a significant participant burden or are subject to considerable intra-individual variation. The continuous secretion of iodide in saliva potentially permits its use as a convenient, non-invasive assessment of status in populations. To assess its likely effectiveness, we reviewed studies analysing the association between salivary iodide concentration (SIC) and dietary iodine intake, urinary iodide concentration (UIC) and/or 24-h urinary iodide excretion (UIE). Eight studies conducted in different countries met the inclusion criteria, including data for 921 subjects: 702 healthy participants and 219 with health conditions. SIC correlated positively with UIC and/or UIE in four studies, with the strength of relationship ranging from r = 0·19 to r = 0·90 depending on sampling protocol, age, and if salivary values were corrected for protein concentration. Additionally, SIC positively correlated with dietary intake, being strongest when saliva was collected after dinner. SIC varied with external factors, including thyroid function, use of some medications, smoking and overall health status. Evidence provided here supports the use of SIC as a viable, low-burden method for determining iodine status in populations. However, small sample sizes and high variability indicates the need for more extensive analyses across age groups, ethnicities, disease states and dietary groups to clarify the relative accuracy and reliability in each case and standardise procedure.

Whole Blood Metal Levels in the Setting of an Oncologic Endoprosthesis: Is There Cause for Concern?

BACKGROUND: Massive modular endoprostheses have become a primary means of reconstruction after oncologic resection of a lower extremity tumor. These implants are commonly made with cobalt-chromium alloys that can undergo wear and corrosion, releasing cobalt and chromium ions into the surrounding tissue and blood. However, there are few studies about the blood metal levels in these patients. QUESTION/PURPOSE: What is the whole blood cobalt and chromium ion level in patients with massive modular endoprostheses? METHODS: We performed a cross-sectional study of our total joints registry to identify patients with a history of an endoprosthetic reconstruction performed at our institution. Patients who were alive at the time of our review in addition to those undergoing an endoprosthetic reconstruction after an oncologic resection were included. Whole blood samples were obtained from 27 (14 male and 13 female) patients with a history of a lower extremity oncologic endoprosthesis. The median time from surgery to blood collection was 8 years (range 6 months to 32 years). Blood samples were collected and stored in metal-free ethylenediaminetetraacetic acid tubes. Samples were analyzed on an inductively coupled plasma mass spectrometer in an International Organization for Standardization seven-class clean room using polytetrafluoroethylene-coated instruments to reduce the risk of metal contamination. The analytical measuring range was 1 to 200 ng/mL for chromium and cobalt. Cobalt and chromium levels were considered elevated when the blood level was ≥ 1 ppb. RESULTS: Cobalt levels were elevated in 59% (16 of 27) of patients, and chromium levels were elevated in 26% (seven of 27). In patients with elevated metal ion values, 15 of 17 patients had a reconstruction using a Stryker/Howmedica Global Modular Replacement System implant. CONCLUSION: Blood metal levels were elevated in patients who received reconstructions using modular oncology endoprostheses Future work is needed to establish appropriate follow-up routines and determine whether and when systemic complications occur because of elevated metal levels and how to potentially address these elevated levels when complications occur. Prospective and retrospective collaboration between multiple centers and specialty societies will be necessary to address these unknown questions in this potentially vulnerable patient group. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Midterm outcomes of total hip arthroplasty after internal hemipelvectomy and iliofemoral arthrodesis.

BACKGROUND AND OBJECTIVES: Recent studies have reported acceptable outcomes after arthrodesis takedown and conversion to total hip arthroplasty (THA); however, there are no reports on outcomes after oncologic resection, which are inherently complex and may portend poorer outcomes. The purpose of this study was to examine the surgical and functional outcomes of patients who underwent prior hemipelvectomy for tumor resection and were later converted to THA. METHODS: All patients who had prior iliofemoral arthrodesis after oncologic resection that were later converted to THA at a single institution were examined. Charts were reviewed for demographic information, operative information, functional outcomes, and complications/reoperations. RESULTS: All three patients in this study were males who underwent internal hemipelvectomies for chondrosarcoma. Patients were converted to THA at a mean of 26 years after arthrodesis. Mean follow-up after conversion to THA was 7.4 years. During this follow-up period, two of the three patients required revision surgery. At last follow-up, the mean Harris Hip Score was 81 and the mean Mayo Hip Score was 67, and all patients were ambulatory without significant pain. CONCLUSIONS: Overall, patients who undergo iliofemoral arthrodesis after oncologic hemipelvectomy and are later converted to THA can expect to have a reasonable outcome, despite a high rate of complications and revision surgery.

Comparison of Hounsfield units and vertebral bone quality score for the prediction of time to pathologic fracture in mobile spine metastases treated with radiotherapy.

OBJECTIVE: Spine metastases are commonly treated with radiotherapy for local tumor control; pathologic fracture is a potential complication of spinal radiotherapy. Both Hounsfield units (HUs) on CT and vertebral bone quality (VBQ) on MRI have been argued to predict stability as measured by odds of pathologic fracture, although it is unclear if there is a difference in the predictive power between the two methodologies. The objective of the present study was to examine whether one methodology is a better predictor of pathologic fracture following radiotherapy for mobile spine metastases. METHODS: Patients who underwent radiotherapy (conventional external-beam radiation therapy, stereotactic body radiation therapy, or intensity-modulated radiation therapy) for mobile spine (C1-L5) metastases at a tertiary care center were retrospectively identified. Details regarding underlying pathology, patient demographics, and tumor morphology were collected. Vertebral involvement was assessed using the Weinstein-Boriani-Biagini (WBB) system. Bone quality of the non-tumor-involved bone was assessed on both pretreatment CT and MRI. Univariable analyses were conducted to identify independent predictors of fracture, and Kaplan-Meier analyses were used to identify significant predictors of time to pathologic fracture. Stepwise Cox regression analysis was used to determine independent predictors of time to fracture. RESULTS: One hundred patients were included (mean age 62.7 ± 11.9 years; 61% male), of whom 35 experienced postradiotherapy pathologic fractures. The most common histologies were lung (22%), prostate (21%), breast (14%), and renal cell (13%). On univariable analysis, the mean HUs of the vertebrae adjacent to the fractured vertebra were significantly lower among those experiencing fracture; VBQ was not significantly associated with fracture odds. Survival analysis showed that average HUs ≤ 132, nonprostate pathology, involvement of ≥ 3 vertebral body segments on the WBB system, Spine Instability Neoplastic Score (SINS) ≥ 7, and the presence of axial pain all predicted increased odds of fracture (all p < 0.001). Cox regression found that HUs ≤ 132 (OR 2.533, 95% CI 1.257-5.103; p = 0.009), ≥ 3 WBB vertebral body segments involved (OR 2.376, 95% CI 1.132-4.987; p = 0.022), and axial pain (OR 2.036, 95% CI 0.916-4.526; p = 0.081) predicted increased fracture odds, while prostate pathology predicted decreased odds (OR 0.076, 95% CI 0.009-0.613; p = 0.016). Sensitivity analysis suggested that an HU threshold of ≤ 132 and a SINS of ≥ 7 identified patients at increased risk of fracture. CONCLUSIONS: The present results suggest that bone density surrogates as measured on CT, but not MRI, can be used to predict the risk of pathologic fracture following radiotherapy for mobile spine metastases. More extensive vertebral body involvement and the presence of mechanical axial pain additionally predict increased fracture odds.

Durability of intercalary endoprosthesis for humeral reconstruction.

INTRODUCTION: The humerus is a common site of metastases and primary tumors. For some patients with a segmental defect and/or diaphyseal cortical destruction a cemented intercalary device may provide a more reliable construct, however data on their use is limited. METHODS: We reviewed 43 (28 male and 15 female) patients treated with an intercalary humeral spacer at a single tertiary referral center between 1989 and 2022. Humeral lesions were most commonly secondary to metastatic disease (n = 29, 68%), with 25 (58%) patients presenting with a pathologic fracture. Mean age and body mass index were 66 years and 27.9 kg/m2 . First generation taper joint device were used in 22 patients and second-generation lap device in 21 patients. RESULTS: Following reconstruction the 2-year overall survival was 30%. Mechanical complications occurred in 11 patients, most commonly aseptic loosening (n = 6, 14%). With death as a competing risk, the cumulative incidence of mechanical failure was 28% at 2-years postoperative. Following the procedure, mean Musculoskeletal Tumor Society scores was 70% and mean shoulder elevation was 87°. CONCLUSION: Reconstruction of the humeral diaphysis with an intercalary endoprosthesis provides restoration of function of the upper extremity, however, is associated with one in four patients having mechanical failure.

Improving R0 Resection Rates With a Posterior-First, 2-Stage Approach for En Bloc Resection of Locally Advanced Primary and Recurrent Anorectal Cancers Involving the Deep Pelvic Sidewall.

BACKGROUND: Using standard anterior approaches, consistent R0 resection of locally advanced primary and recurrent rectal and anal cancer involving the deep pelvic sidewall may be unattainable. Therefore, to improve R0 resection rates, we have used a posterior-first, then anterior 2-stage approach to resection of tumors in this location. OBJECTIVE: To assess the R0 resection rate and surgical outcomes of the first 10 patients operated on using this approach. DESIGN: We conducted a retrospective case series review of our prospectively maintained surgical pathology and tumor registries. SETTING: This study was conducted at the Mayo Clinic in Rochester, Minnesota. PATIENTS: Ten patients (6 female individuals, median age 53.5 years) with primary or recurrent anal or rectal cancer treated with a posterior-first, then anterior 2-stage approach were identified. MAIN OUTCOME MEASURES: The primary outcome measures were the R0 resection rate and surgical outcomes. RESULTS: An R0 resection was achieved in all 10 patients. Nine patients developed 1 or more 30-day Clavien-Dindo grade III complications. Nine patients developed gluteal wound complications ranging from superficial wound dehiscence to flap necrosis. During the follow-up period, 4 patients were found to have metastatic disease and 1 patient had local re-recurrence. LIMITATIONS: Small cohort with heterogeneous tumors and a short follow-up duration. CONCLUSION: A posterior-first, then anterior 2-stage approach has allowed us to achieve consistent R0 resection margins in locally advanced primary and recurrent rectal and anal cancers involving the deep pelvic sidewall. Poor wound healing of the posterior gluteal incision is a common complication. See Video Abstract. MEJORANDO LAS TASAS DE RESECCIN R CON UN ABORDAJE DE DOS ETAPAS PRIMERO POSTERIOR PARA LA RESECCIN EN BLOQUE DE CNCERES ANORRECTALES PRIMARIOS Y RECURRENTES LOCALMENTE AVANZADOS QUE AFECTAN LA PARED LATERAL PLVICA PROFUNDA: ANTECEDENTES:Utilizando abordajes anteriores estándares, la resección R0 consistente del cáncer de recto y ano primario y recurrente localmente avanzado involucrando la pared lateral pélvica profunda puede ser inalcanzable. Por lo tanto, para mejorar las tasas de resección R0, hemos empleado un abordaje de 2 etapas primero posterior y luego anterior para la resección de tumores en esta ubicación.OBJETIVO:Este estudio tuvo como objetivo evaluar la tasa de resección R0 y los resultados quirúrgicos de los primeros 10 pacientes operados con este abordaje.DISEÑO:Realizamos una revisión retrospectiva de series de casos de nuestros registros de patología quirúrgica y tumores mantenidos prospectivamente.AJUSTE:Este estudio se realizó en la Clínica Mayo en Rochester, Minnesota, EE. UU.PACIENTES:Se identificaron diez pacientes (6 mujeres, mediana de edad 53.5 años) con cáncer anal o rectal primario o recurrente tratados con un abordaje de dos etapas, primero posterior y luego anterior.PRINCIPALES MEDIDAS DE RESULTADO:Las medidas de resultado primarias fueron la tasa de resección R0 y los resultados quirúrgicos.RESULTADOS:Se logró una resección R0 en los 10 pacientes. Nueve pacientes desarrollaron una o más complicaciones de grado III de Clavien-Dindo a los 30 días. Nueve pacientes desarrollaron complicaciones de la herida del glúteo que variaron desde dehiscencia superficial de la herida hasta necrosis del colgajo. Durante el período de seguimiento, se encontró que 4 pacientes tenían enfermedad metastásica y un paciente tuvo recurrencia local.LIMITACIONES:Cohorte pequeño con tumores heterogéneos y corta duración de seguimiento.CONCLUSIÓN:Un abordaje en 2 etapas, primero posterior y luego anterior, nos ha permitido lograr márgenes de resección R0 consistentes en cánceres de recto y anal primarios y recurrentes localmente avanzados que afectan la pared lateral pélvica profunda. La mala cicatrización de la incisión glútea posterior es una complicación común. (Traducción-Dr. Aurian Garcia Gonzalez).

Reconstruction following oncological iliosacral resection.

Aims: The sacroiliac joint (SIJ) is the only mechanical connection between the axial skeleton and lower limbs. Following iliosacral resection, there is debate on whether reconstruction of the joint is necessary. There is a paucity of data comparing the outcomes of patients undergoing reconstruction and those who are not formally reconstructed. Methods: A total of 60 patients (25 females, 35 males; mean age 39 years (SD 18)) undergoing iliosacral resection were reviewed. Most resections were performed for primary malignant tumours (n = 54; 90%). The mean follow-up for surviving patients was nine years (2 to 19). Results: Overall, 27 patients (45%) were reconstructed, while 33 (55%) had no formal reconstruction. There was no difference in the use of chemotherapy (p = 1.000) or radiotherapy (p = 0.292) between the groups. Patients with no reconstruction had a mean larger tumour (11 cm (SD 5) vs 8 cm (SD 4); p = 0.014), mean shorter operating times (664 mins (SD 195) vs 1,324 mins (SD 381); p = 0.012), and required fewer blood units (8 (SD 7) vs 14 (SD 11); p = 0.012). Patients undergoing a reconstruction were more likely to have a deep infection (48% vs 12%; p = 0.003). Nine reconstructed patients had a hardware failure, with five requiring revision. Postoperatively 55 (92%) patients were ambulatory, with no difference in the proportion of ambulatory patients (89% vs 94%; p = 0.649) or mean Musculoskeletal Tumor Society Score (59% vs 65%; p = 0.349) score between patients who did or did not have a reconstruction. The ten-year disease-specific survival was 69%, with no difference between patients who were reconstructed and those who were not (78% vs 45%; p = 0.316). There was no difference in the rate of metastasis between the two groups (hazard ratio (HR) 2.78; p = 0.102). Conclusion: Our results demonstrate that SIJ reconstruction is associated with longer operating times, greater need for blood transfusion, and more postoperative infections, without any improvement in functional outcomes when compared to patients who did not have formal SIJ reconstruction.

Activity of pembrolizumab and lenvatinib in mismatch repair deficient (dMMR) endometrial cancer patients who have failed pembrolizumab monotherapy: A case series.

To evaluate the efficacy of the combination of pembrolizumab and lenvatinib in MMR deficient (dMMR) endometrial cancer (EC) patients who previously failed to respond to single-agent pembrolizumab. A retrospective review of MMR deficient endometrial cancer patients was performed. Patients who failed to respond to pembrolizumab as a single-agent and subsequently received a combination of pembrolizumab and lenvatinib were analyzed. RECIST 1.1 criteria was used to establish clinical response (complete response, partial response, stable disease, and progression) based on CT and/or PET, comparing imaging before and after the addition of lenvatinib. Radiologic review was conducted by an independent radiologist. Eight patients with dMMR EC meeting treatment criteria were identified. The patients' ages ranged from 54 to 80 and all tumors identified were of endometrioid histology. Initial pathologic stage ranged from FIGO stage IB to IVB and recurrence confirmed via imaging or tissue biopsy. Patients received a median of 14 cycles of therapy with pembrolizumab and lenvatinib (range 1-39). All patients had decrease in measurable disease with an objective response of 75 % (PR 62.5 %, CR 12.5 %). Both patients who received the initial recommended dose of 20 mg daily required a dose reduction. Based on this retrospective study, patients with dMMR EC without significant benefit from pembrolizumab monotherapy have a significant clinical response after the addition of lenvatinib. Combination therapy should be considered for dMMR EC patients who fail pembrolizumab monotherapy.

Response of low HER2-expressing ovarian carcinosarcoma to trastuzumab deruxtecan, a case report.

•Treatment options are limited for recurrent ovarian carcinosarcoma (OCS).•A patient with HER2 1 + IHC and negative FISH amplification was treated with trastuzumab deruxtecan.•A durable partial response was achieved, suggesting a possible treatment option for OCS patients with HER2 expression.

Interpretations of High-Order Transient Absorption Spectroscopies.

Transient absorption (TA) spectroscopy is an invaluable tool for determining the energetics and dynamics of excited states. When pump intensities are sufficiently high, TA spectra include both the generally desired third-order response and responses that are higher in order in the field amplitudes. Recent work demonstrated that pump-intensity-dependent TA measurements allow separating the orders of response, but the information content in those higher orders has not been described. We give a general framework for understanding high-order TA spectra. We extend to higher order the fundamental processes of standard TA: ground-state bleach (GSB), stimulated emission (SE), and excited-state absorption (ESA). Each order introduces two new processes: SE and ESA from previously inaccessible highly excited states and negations of lower-order processes. We show the new spectral and dynamical information at each order and show how the relative signs of the signals in different orders can be used to identify which processes dominate.

Oncological and functional outcomes after resection of malignant tumours of the scapula.

Aims: The scapula is a rare site for a primary bone tumour. Only a small number of series have studied patient outcomes after treatment. Previous studies have shown a high rate of recurrence, with functional outcomes determined by the preservation of the glenohumeral joint and deltoid. The purpose of the current study was to report the outcome of patients who had undergone tumour resection that included the scapula. Methods: We reviewed 61 patients (37 male, 24 female; mean age 42 years (SD 19)) who had undergone resection of the scapula. The most common resection was type 2 (n = 34) according to the Tikhoff-Linberg classification, or type S1A (n = 35) on the Enneking classification. Results: The ten-year disease-specific survival was 76%. High tumour grade (hazard ratio (HR) 4.27; p = 0.016) and a total resection of the scapula (HR 3.84; p = 0.015) were associated with worse survival. The ten-year metastasis-free and local recurrence-free survivals were 82% and 86%, respectively. Total scapular resection (HR 6.29; p = 0.004) was associated with metastatic disease and positive margins were associated with local recurrence (HR 12.86; p = 0.001). At final follow-up, the mean shoulder forward elevation and external rotation were 79° (SD 62°) and 27° (SD 25°), respectively. The most recent functional outcomes evaluated included the mean Musculoskeletal Tumor Society Score (76% (SD 17%)), the American Shoulder and Elbow Score (73% (SD 20%)), and the Simple Shoulder Test (7 (SD 3)). Preservation of the glenoid (p = 0.001) and scapular spine (p < 0.001) improved clinical outcomes; interestingly, preservation of the scapular spine without the glenoid improved outcomes (p < 0.001) compared to preservation of the glenoid alone (p = 0.05). Conclusion: Resection of the scapula is a major undertaking with an oncological outcome related to tumour grade, and a functional outcome associated with the status of the scapular spine and glenoid. Positive resection margins are associated with local recurrence.

Association between immunohistochemical markers and tumor progression following resection of spinal chordomas: a multicenter study.

OBJECTIVE: Chordomas are slow-growing tumors derived from notochord remnants. Despite margin-negative excision and postoperative radiation therapy, spinal chordomas (SCs) often progress. The potential of immunohistochemical (IHC) markers, such as epithelial membrane antigen (EMA), combined with machine learning algorithms to predict long-term (≥ 12 months) postoperative tumor progression, has been understudied. The authors aimed to identify IHC markers using trained tree-based algorithms to predict long-term (≥ 12 months) postoperative tumor progression. METHODS: The authors reviewed the records of patients who underwent resection of SCs between January 2017 and June 2021 across the Mayo Clinic enterprise. Demographics, type of treatment, histopathology, and other relevant clinical factors were abstracted from each patient's record. Low tumor progression was defined as more than a 94.3-mm3 decrease in the tumor size at the latest radiographic follow-up. Decision trees and random forest classifiers were trained and tested to predict the long-term volumetric progression after an 80/20 data split. RESULTS: Sixty-two patients diagnosed with and surgically treated for SC were identified, of whom 31 were found to have a more advanced tumor progression based on the tumor volume change cutoff of 94.3 mm3. The mean age was 54.3 ± 13.8 years, and most patients were male (62.9%) and White (98.4%). The most common treatment modality was subtotal resection with radiation therapy (35.5%), with proton beam therapy being the most common (71%). Most SCs were sacrococcygeal (41.9%), followed by cervical (32.3%). EMA-positive SCs had a postoperative progression risk of 67%. Pancytokeratin-positive SCs had a progression rate of 67%; however, patients with S100 protein-positive SCs had a 54% risk of progression. The accuracy of this model in predicting the progression of unseen test data was 66%. Pancytokeratin (mean minimal depth = 1.57), EMA (mean minimal depth = 1.58), cytokeratin A1/A3 (mean minimal depth = 1.59), and S100 protein (mean minimal depth = 1.6) predicted the long-term volumetric progression. Multiway variable importance plots show the relative importance of the top 10 variables based on three measures of varying significance and their predictive role. CONCLUSIONS: These IHC variables with tree-based machine learning tools successfully demonstrate a high capacity to identify a patient's tumor progression pattern with an accuracy of 66%. Pancytokeratin, EMA, cytokeratin A1/A3, and S100 protein were the IHC drivers of a low tumor progression. This shows the power of machine learning algorithms in analyzing and predicting outcomes of rare conditions in a small sample size.

A phase III, multicenter, randomized study of olvimulogene nanivacirepvec followed by platinum-doublet chemotherapy and bevacizumab compared with platinum-doublet chemotherapy and bevacizumab in women with platinum-resistant/refractory ovarian cancer.

BACKGROUND: Treatment options for patients with platinum-resistant/refractory ovarian cancers are limited and only marginally effective. The development of novel, more effective therapies addresses a critical unmet medical need. Olvimulogene nanivacirepvec (Olvi-Vec), with its strong immune modulating effect on the tumor microenvironment, may provide re-sensitization to platinum and clinically reverse platinum resistance or refractoriness in platinum-resistant/refractory ovarian cancer. PRIMARY OBJECTIVE: The primary objective is to evaluate the efficacy of intra-peritoneal Olvi-Vec followed by platinum-based chemotherapy and bevacizumab in patients with platinum-resistant/refractory ovarian cancer. STUDY HYPOTHESIS: This phase III study investigates Olvi-Vec oncolytic immunotherapy followed by platinum-based chemotherapy and bevacizumab as an immunochemotherapy evaluating the hypothesis that such sequential combination therapy will prolong progression-free survival (PFS) and bring other clinical benefits compared with treatment with platinum-based chemotherapy and bevacizumab. TRIAL DESIGN: This is a multicenter, prospective, randomized, and active-controlled phase III trial. Patients will be randomized 2:1 into the experimental arm treated with Olvi-Vec followed by platinum-doublet chemotherapy and bevacizumab or the control arm treated with platinum-doublet chemotherapy and bevacizumab. MAJOR INCLUSION/EXCLUSION CRITERIA: Eligible patients must have recurrent, platinum-resistant/refractory, non-resectable high-grade serous, endometrioid, or clear-cell ovarian, fallopian tube, or primary peritoneal cancer. Patients must have had ≥3 lines of prior chemotherapy. PRIMARY ENDPOINT: The primary endpoint is PFS in the intention-to-treat population. SAMPLE SIZE: Approximately 186 patients (approximately 124 patients randomized to the experimental arm and 62 to the control arm) will be enrolled to capture 127 PFS events. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Expected complete accrual in 2024 with presentation of primary endpoint results in 2025. TRIAL REGISTRATION: NCT05281471.