Adjuvant Surgery Research Articles

Circulating tumor DNA (ctDNA) detection of molecular residual disease (MRD) as a potential biomarker in localized soft tissue sarcoma (STS).

11547 Background: Surgery and (neo)adjuvant radiotherapy are the mainstay curative treatments for localized STS. Despite treatment, approximately 50% of STS patients (pts) experience metastatic relapse and routine use of adjuvant systemic therapy (AST) remains controversial. The presence of ctDNA following curative treatment of STS is a potential biomarker for MRD and may identify patients who benefit from AST. Given the genomic heterogeneity of STS, a histology-agnostic approach to ctDNA detection in this population is desirable. Methods: Pts with localized, high risk (size ≥ 5cm, grade ≥ 2) disease were enrolled prior to (neo) adjuvant radiotherapy and surgery. Blood for ctDNA was collected at diagnosis; post-radiotherapy, post-surgery and every 3 months for up to 2 years. Whole exome sequencing (WES) of archival tumor- and matched buffy coat-DNA were carried out to identify somatic variants. Personalized and tumor-informed, multiplex PCR next generation sequencing-based ctDNA assay (Signatera™ assay) was performed on plasma obtained at the serial timepoints. A sample level positive call required ≥ 2 variants above a confidence calling threshold. Absolute ctDNA levels were expressed as mean tumor molecules per milliliter (MTM/ml) of plasma, based on variant allele frequencies and quantity of cell free DNA. Standard radiologic surveillance (every 3 months) was performed following surgery. The primary endpoint was a ctDNA detection rate of 70% at diagnosis. Secondary endpoints included MRD detection and correlation of ctDNA levels with disease relapse. Results: Seventy-six plasma samples from 10 pts [8 males and 2 females; median age 64 years (range 46–84)] were obtained prospectively. STS subtypes were undifferentiated pleomorphic sarcoma (n = 4), myxofibrosarcoma (n = 2), dedifferentiated liposarcoma (n = 2), myxoid liposarcoma (n = 1), and pleomorphic liposarcoma (n = 1). All tumors successfully underwent WES with adequate data quality for Signatera™ assay design. The personalized ctDNA assay was performed on a median of 7 plasma samples per patient (range: 5 – 10). ctDNA was detected in 7 pts (70%) at diagnosis, with median ctDNA level of 1.6 MTM/ml (range: 0.2 – 137.8), achieving the study primary endpoint. Immediate post-surgery samples were negative in all pts. However, ctDNA was detected in 2 out of 2 pts who developed metastatic disease during follow-up. Conclusions: Personalized tumor-informed ctDNA assays in localized high-risk STS at diagnosis are feasible. In this series, all patients had undetectable levels of ctDNA post-surgery and patients who experienced disease relapse demonstrated a detectable rise in ctDNA levels. Further interrogation of this approach for detection of post-treatment MRD as a possible biomarker of benefit from AST is ongoing.

Adjuvant chemotherapy after curative D2 gastrectomy in Latin American patients with gastric cancer.

BackgroundGastric cancer (GC) is the fourth most common cause of cancer deaths around the world and the first cause of cancer deaths in Peru; however, there are no prospective trials for adjuvant chemotherapy in GC after curative gastrectomy in this country. The objective of this study was to evaluate the effectiveness of adjuvant chemotherapy in stage II–III gastric cancer patients who underwent D2 gastrectomy.MethodsWe included patients with stage II–III gastric cancer who underwent radical gastrectomy and D2 dissection between 2014 and 2016 at our institution. Patients received 3-week cycles of capecitabine (1,000 mg/m2 twice daily on days 1–14) plus oxaliplatin (130 mg/m2 on day 1) for 6 months. Survival curves were estimated with the Kaplan–Meier method, and the Cox proportional hazards model was used to identify prognostic factors for survival.ResultsIn total, 173 patients were included: 100 (57.8%) patients received adjuvant chemotherapy and surgery (AChS) and 73 (42.2%) surgery alone (SA). Three-year disease-free survival (DFS) was higher in the AChS groups (69%) than in the SA group (52.6%) (p = 0.034). Regarding overall survival (OS), 31 patients (31%) died in the AChS group compared with 34 (46.6%) in the SA group (p = 0.027). In the multivariate analysis, adjuvant chemotherapy was an independent prognostic factor for DFS (HR = 0.60; 95% CI = 0.37–0.97; p = 0.036) and OS (HR = 0.58; 95% CI = 0.36–0.95; p = 0.029). ACh showed consistent benefit in DFS and OS for patients with albumin >3.5 g/dL, lymphovascular and perineural invasion, pT4, pN2–3, pathologic stage (PS) IIIA and IIIB and lymph node ratio (LNR) > 13.1.ConclusionThese data suggest that adjuvant capecitabine and oxaliplatin reduce the recurrence and mortality in patients with stage II–III gastric cancer who underwent D2 gastrectomy. PS IIIA and IIIB and LNR > 13.1 benefited more from receiving adjuvant chemotherapy and poorly cohesive gastric carcinoma did not significantly reduce the rates of survival.

Clinical outcomes in central nervous system solitary-fibrous tumor/hemangiopericytoma: a STROBE-compliant single-center analysis

BackgroundSolitary fibrous tumor (SFT) and hemangiopericytoma (HPC) are rare mesenchymal tumors in the central nervous system with a high tendency to relapse, having a significant impact on quality of life (QoL). Due to the rarity of intracranial SFT/HPC, the prognostic factors and optimal treatment remain to be elucidated. Meanwhile, quality of life in patients with intracranial SFT/HPC is seldomly concerned. Thus, we aim to survey about the quality of life and underline some aspects demanding concern in intracranial SFT/HPC treatment through summarizing our case series in recent ten years.MethodsPatients with intracranial SFT/HPC who underwent surgical resection from January 2009 to June 2019 were included in the study. Clinical features, such as age, gender, and resection extent, were collected. The EuroQol Five Dimensions Questionnaire (EQ-5D) was used to assess the patients’ quality of life (QoL). Prognosis factors related to progression-free survival (PFS) and overall survival (OS) were also evaluated.ResultsThirty-six patients with a mean follow-up period of 61.6 months (range 13–123 months) were included in this study. Sixteen (44.4%) patients achieved gross total resection (GTR). Fourteen patients (38.9%) with tumor progression experienced adjuvant radiotherapy (11.1%) or Gamma Knife surgery (GKS, 27.8%). According to the 2016 WHO classification, there were 6 (16.7%) grade I SFT/HPC, 11 (30.5%) grade II SFT/HPC, and 19 (52.8%) grade III SFT/HPC. The PFS and OS were 29 months (range 4–96 months) and 38 months (range 4–125 months). The median EQ5D-3 L tariff with or without progression was 0.617 (95% CI 0.470–0.756) and 0.939 (95% CI 0.772–0.977) respectively. Gross total resection (GTR, p = 0.024) and grade I SFT/HPC (p = 0.017) were significantly associated with longer PFS. In multivariate analysis, GTR (HR 0.378, 95% CI 0.154–0.927) and adjuvant therapy (HR 0.336, 95% CI 0.118–0.956) result in significantly longer PFS in patients with SFT/HPC.ConclusionsPatients underwent GTR and adjuvant therapy had longer PFS. Similarly, patients with lower WHO grade had relatively longer PFS. Therefore, GTR is advocated for the treatment of SFT/HPC. And adjuvant therapy such as GKS could be an alternative treatment for patients who underwent STR or with tumor progression. Further, the QoL decreased in patients with tumor progression and metastasis, and more attention is demanded to the QoL of intracranial SFT/HPC patients.

Intra-articular injection of stromal vascular fraction for knee degenerative joint disease: a concise review of preclinical and clinical evidence.

Autologous fat-derived stromal vascular fraction (SVF) is a mixed cell population that has been used for many years in regenerative plastic surgery. In terms of animal and clinical research, this concise review was performed to evaluate the efficacy of SVF in knee degenerative joint disease (KDJD), which could cause pain, disability and severely affect patients' lives. Thirteen studies retrieved and screened from the databases were included, including six animal studies and seven clinical trials. The meta-analysis of clinical research shows that intra-articular injection of SVF, in combination with adjuvant surgery, could alleviate pain and improve early functional recovery for patients with KDJD at Kellgren-Lawrence (KL) grades II-III.

Effect of adjuvant chemotherapy on periosteal osteosarcoma: a systematic review.

The effects of adjuvant chemotherapy on periosteal osteosarcoma are controversial. Therefore, we conducted a systematic review of studies comparing mortality, local recurrence, distant metastasis and secondary malignancy incidence among patients who underwent surgery and (neo-) adjuvant chemotherapy or surgery alone for periosteal osteosarcoma without distant metastases at diagnosis. Of the 210 studies identified in the search, 13 were included in this study, involving 291 patients with periosteal osteosarcoma in total. The mortality rates in the surgery and (neo-) adjuvant chemotherapy and surgery alone groups were 11.3% (8/71) and 16.3% (16/98), respectively. The overall pooled odds ratio was 0.89 (P=0.800). The local recurrence rate in the surgery and (neo-) adjuvant chemotherapy group was 12.1% (8/66), while that in the surgery alone group was 17.6% (13/74). The overall pooled odds ratio was 1.31 (P=0.601). The distant metastasis rate in the surgery and (neo-) adjuvant chemotherapy group was 15.2% (10/66) and that in the surgery alone group was 10.8% (8/74). The overall pooled odds ratio was 1.51 (P=0.444). The incidence of secondary malignancy in the surgery and (neo-) adjuvant chemotherapy group was 7.6% (9/118) and that in the surgery alone group was 2.7% (2/74). The overall pooled odds ratio was 2.29 (P=0.187). Adjuvant chemotherapy did not appear to improve the prognosis of patients with periosteal osteosarcoma. No association was found between the use of adjuvant chemotherapy and development of secondary malignancies.

ASO Author Reflections: Role of Adjuvant Surgery in Locally Advanced Cervical Cancer: An Unresolved Issue.

ASO Author Reflections: Role of Adjuvant Surgery in Locally Advanced Cervical Cancer: An Unresolved Issue.

Interventional Palliation of Painful Extraspinal Musculoskeletal Metastases.

The musculoskeletal system is commonly involved by metastases, and skeletal-related events such as intractable pain due to direct osseous tumor involvement, pathologic fracture, and neurologic deficits as a result of nerve compression often adversely affect patient's quality of life. There have been substantial advances in percutaneous minimally invasive musculoskeletal oncologic interventions for the management of patients with musculoskeletal metastases including thermal ablations, cementation with or without osseous reinforcement via implants, osteosynthesis, neurolysis, and palliative injections which are progressively incorporated in clinical practice. These interventions are performed, in conjunction with or supplemented by adjuvant radiation therapy, systemic therapy, surgery, or analgesics, to achieve durable pain palliation, local tumor control, or cure. This article reviews minimally invasive percutaneous image-guided musculoskeletal oncologic interventions for the management of patients with extraspinal musculoskeletal metastases.

Clinical Impact of Pathologic Residual Tumor in Locally Advanced Cervical Cancer Patients Managed by Chemoradiotherapy Followed by Radical Surgery: A Large, Multicenter, Retrospective Study

BackgroundExclusive chemoradiation (E-CT/RT) represents the standard of treatment for locally advanced cervical cancer (LACC). Chemoradiation (CT/RT) followed by radical surgery (RS) may play a role for patients with a suboptimal response to CT/RT or in low-income countries with limited access to radiotherapy. Histologic assessment of residual tumor after CT/RT and RS allows accurate definition of prognostic categories.MethodsData on patients with FIGO stages 1B2 to 4A cervical cancer managed by CT/RT and RS from June 1996 to March 2020 were retrospectively analyzed. Pathologic response on the cervix was defined as complete (pCR), microscopic (persistent tumor foci ≤ 3 mm) (pmicroR), or macroscopic (persistent tumor foci > 3 mm) (pmacroR). Lymph node (LN) residual tumor was classified as absent or present.ResultsThe 701 patients in this study underwent CT/RT and RS. Of the 701 patients, 293 (41.8%) had pCR, 188 (26.8%) had pmicroR, and 220 (31.4%) had pMacroR. Residual tumor was found in the pelvic lymph nodes of 66 (9.4%) patients and the aortic lymph nodes of 29 (4.1%) patients. The 5-year DFS and OS were respectively 86.6% and 92.5% in the pCR cases, 80.3% and 89.1% in the pmicroR cases, and 56.2% and 68.8% in the pmacroR cases. Among the patients with lymph node residual tumor, the 5-year DFS and OS were respectively 16.7% and 40% in the pCR cases, 35.4% and 53.3% in the pmicroR cases, and 31.7% and 31.1% in the pmacroR cases. Cervical residual tumor,, positive pelvic LNs, and positive aortic LNs were associated with worse DFS and OS in both the uni- and multivariate analyses.ConclusionsPersistence of pathologic residual tumor on the cervix and LNs after CT/RT are reliable predictors of survival for LACC patients undergoing CT/RT and adjuvant surgery.

Chronic unilateral leg warty lesion: clinical image and literature review

54 years old diabetic male presented with history of with painless multiple progressive warty lesions on the right lower two third of the left leg remain undiagnosed for twelve years. It was spreading and growing relentlessly, not responding to medication prescribed by multiple doctors and patient thought of a uncurable disease. The biopsy came confirmatory. Antifungal therapy along with surgical excision hasten up the healing. An adequate biopsy is a must in undiagnosed skin lesion. Specific medical therapy and adjuvant surgery give early relief.

Adjuvant stereotactic body radiotherapy after marginal resection for hepatocellular carcinoma with microvascular invasion: A randomised controlled trial

BackgroundMarginal resection frequently occurred in hepatectomy for hepatocellular carcinoma (HCC), leading to increased local recurrence, especially among patients with microvascular invasion (MVI). Stereotactic body radiotherapy (SBRT) showed effectiveness in controlling tumour and tumour thrombosis. This study aimed to investigate the efficacy of SBRT, targeting on suboptimal resection margin, as adjuvant setting in MVI-positive HCC. MethodsThis was a single-centre randomised controlled trial conducted in Eastern Hepatobiliary Surgery Hospital, Shanghai, China. Participants with MVI-positive HCC receiving marginal resection were randomly assigned to the postoperative adjuvant SBRT or surgery alone (SA) group. SBRT was delivered by the CyberKnife® system with marker tracking devices, targeting on resection margin one month after surgery. The disease-free survival (DFS) and overall survival (OS) were compared between the groups, and the adverse events (AEs) were monitored. This trial was registered on ClinicalTrials.gov, NCT04891874. FindingsA total of 76 participants were enrolled, with 38 in each group. The one-, three-, and five-year DFS rates were 92.1%, 65.8%, and 56.1% in SBRT group versus 76.3%, 36.8%, and 26.3% in SA group, respectively (p = 0.005). The one-, three-, and five-year OS rates were 100%, 89.5%, and 75.0% in SBRT group versus 100.0%, 68.4%, and 53.7% in SA group, respectively (p = 0.053). The total dose of SBRT for single participant was 35 Gy, and the biological effective dose (BED) was 59.5 Gy. The overall incidence of radiotherapy-related AE was 31.6% (12/38), and no grade 3 or higher grade AE was developed. InterpretationSBRT on the resection margin provides a safe therapeutic modality of adjuvant setting in MVI-positive HCC with suboptimal resection margin. It prevents local recurrence and improves DFS. Trial registration numberNCT04891874.

The Affects of Adjuvant Radiotherapy on Survival in Elderly Patients with Advanced Head & Neck Squamous Cell Carcinoma

<h3>Purpose/Objective(s)</h3> For locally advanced head and neck squamous cell carcinoma (HNSCC), adjuvant radiotherapy (RT) following definitive surgical resection has been widely shown to confer a survival benefit. However, the presence of this survival benefit for elderly patients has not been clearly demonstrated. Given the numerous morbidities associated with RT, we sought to investigate the difference in overall survival (OS) associated with adjuvant therapy in elderly patients (80+). <h3>Materials/Methods</h3> The National Cancer Database (NCDB) was queried for all cases of HNSCC between 2004-2016 using ICD-O-3 histology and morphology codes. Those with advanced disease, defined as pathologic T3/T4 and/or N2b or greater, were selected for inclusion. Exclusion criteria included those with HPV-positive disease, distant metastasis, positive surgical margins, and/or death within 30 days of surgery. Patients who received neoadjuvant treatment and/or systemic therapy were additionally excluded. Patients treated with surgical resection alone were compared to those treated with surgery + adjuvant RT. OS was compared between these groups in patients younger than 80 and separately for those 80+ using Kaplan meier analysis. Odds ratios (OR) were assessed using Cox proportional hazards to account for differences in patient characteristics, primary site, and HNSCC stage. <h3>Results</h3> NCDB identified 16,504 cases meeting inclusion criteria with 7,375 (44.7%) treated with surgery alone and 9,129 (55.3%) receiving adjuvant RT. The mean age was 63.8 years (SD = 12.0) with 89.0% of patients aged <80 and 11.0% aged 80+. In the younger cohort, adjuvant RT was associated with a significant increase in OS relative to surgery alone when assessed at 1 year (88.4% vs. 83.8%, p=<0.001), 3 years (64.0% vs. 59.2%, p=<0.001) and 5 years (52.8% vs 47.2%, p=<0.001). In the elderly cohort, there was no significant difference in OS between adjuvant RT and surgery alone when measured at 1 year (73.4% vs. 74.8%, 0.296), 3 years (45.8% vs. 41.8%, p=0.465), or 5 years (28.2% vs. 27.7% p=0.759). Cox regression was utilized to assess the OR for 5-year OS associated with adjuvant RT after accounting for differences in primary site, T-stage, and N-stage. In patients under 80, surgery alone remained a significant predictor of 5-year mortality with an OR of 1.32 (95% CI 1.25-1.39, p=<0.001). In the elderly cohort, there was no significant difference between groups with surgery alone carrying an OR of 1.10 (95% CI 0.96-1.25, p=0.169). <h3>Conclusion</h3> In elderly patients undergoing definitive surgical treatment of locally advanced HSNCC, adjuvant RT may not provide a similar overall survival benefit relative to younger patients. Further research is needed to explore differences in disease-specific survival and quality of life to guide shared decision making in this patient population.

Impact of the COVID-19 Pandemic on Colorectal Cancer Care in the Netherlands: A Population-based Study

IntroductionThe COVID-19 pandemic disrupted health care services worldwide. In the Netherlands, the first confirmed COVID-19 infection was on February 27, 2020. We aimed to investigate the impact of the pandemic on colorectal cancer care in the Netherlands. MethodsColorectal cancer patients who were diagnosed in 25 hospitals in weeks 2 to 26 of the year 2020 were selected from the Netherlands Cancer Registry (NCR) and divided in 4 periods. The average number of patients treated per type of initial treatment was analyzed by the Mantel-Haenszel test adjusted for age. Median time between diagnosis and treatment and between (neo)adjuvant therapy and surgery were analyzed by the Mann Whitney test. Percentages of (acute) resection, stoma and (neo)adjuvant therapy were compared using the Chi-squared test. ResultsIn total, 1,653 patients were included. The patient population changed during the COVID-19 pandemic regarding higher stage and more clinical presentation with ileus at time of diagnosis. Slight changes were found regarding type of initial treatment. Median time between diagnosis and treatment decreased on average by 4.5 days during the pandemic. The proportion of colon cancer patients receiving a stoma significantly increased with 6.5% during the pandemic. No differences were found in resection rate and treatment with (neo)adjuvant therapy. ConclusionDespite the disruptive impact of the COVID-19 pandemic on global health care, the impact on colorectal cancer care in the Netherlands was limited.

Oil Cyst Formation after Lower Blepharoplasty with Fat Grafts.

Fat grafting is increasingly used as an adjuvant surgery to blepharoplasty to refill the volume loss of an aged face and promote cellular regeneration. Complications, such as hematoma, infection, seroma, and palpable mass, may occur. We collected the patients that underwent lower blepharoplasty combined with fat graft to evaluate the incidence of oil cyst formation in the lower eyelid and to identify risk factors. A retrospective review was performed of all patients who underwent lower or total blepharoplasty combined with fat graft at the authors' institution between January 2018 and June 2020. Complication rates were observed, and associations between preoperative variables and outcomes were assessed. A total of 119 patients were included in the series (all bilateral, 238 eyelids). The average patient age was 54.88 ± 11.94 years, and the average grafted fat was 1.88 ± 1.0 mL. On a per-eyelid basis for all patients, the complication rate of oil cyst formation was 6.72% (16 of 238 eyelids). The occurrence of oil cyst formation was associated with hypertension (P = 0.012; adjusted odds ratio, 9.27; 95% confidence interval, 1.62-52.99) and diabetes mellitus (P = 0.005; adjusted odds ratio, 14.02; 95% confidence interval, 2.22-88.45), but not associated with anticoagulants use (P = 0.931), age (P = 0.784), sex (P = 0.317), or fat volume (P = 0.215). The mean interval between the fat graft procedure and oil cyst noted was 236.5 ± 118.9 days. Oil cyst in lower eyelid can be defined as a palpable, firm, and persistent subcutaneous cystic lesion found postoperatively in any size during physical examination. The complication rate of oil cyst formation occurring after lower blepharoplasty with autologous fat grafting is 6.72%. Hypertension and diabetes mellitus maybe are risk factors of oil cyst formation. Steroid injection, needle capsulotomy, liposuction, and excision are safe and effective treatments. Reduce surgical trauma by diminishing anterior lamina trauma and capsulopalpebral fascia repair might decrease the complication rate of oil cyst formation.Transconjunctival lower blepharoplasty with fat graft or 2-stage surgery may be a choice to prevent oil cyst formation.

Will the collaboration of surgery and external radiotherapy open new avenues for hepatocellular carcinoma with portal vein thrombosis?

Portal invasion of hepatocellular carcinoma (HCC) occurs in 12.5%-40% of patients diagnosed with cancer and yields poor clinical outcomes. Since it is a common cause of inoperability, sorafenib was regarded as the standard treatment for HCC in the Barcelona Clinic of Liver Cancer guidelines. However, the median survival of the Asian population was only approximately 6 mo, and the tumor response rate was less than moderate (< 5%). Various locoregional modalities were performed, including external beam radiotherapy (EBRT), transarterial chemoembolization, hepatic arterial infusion chemotherapy, and surgery, alone or in combination. Among them, EBRT is a noninvasive method and can safely treat tumors involving the major vessels. Palliative EBRT has been commonly performed, especially in East Asian countries, where locally invasive HCC is highly prevalent. Although surgery is not commonly indicated, pioneering studies have demonstrated encouraging results in recent decades. Furthermore, the combination of neo- or adjuvant EBRT and surgery has been recently used and has significantly improved the outcomes of HCC patients, as reported in a few randomized studies. Regarding systemic modality, a combination of novel immunotherapy and vascular endothelial growth factor inhibitor showed results superior to that of sorafenib as a first-line agent. Future clinical trials investigating the combined use of these novel agents, surgery, and EBRT are expected to improve the prognosis of HCC with portal invasion.

Abstract OT2-11-09: Lidera breast cancer: A phase III adjuvant study of giredestrant (GDC-9545) vs physician’s choice of endocrine therapy (ET) in patients (pts) with estrogen receptor-positive, HER2-negative early breast cancer (ER+/HER2- EBC)

Abstract BACKGROUND ETs that target ER activity and/or estrogen synthesis are the mainstay of ER+ BC treatment. Despite best management, up to 20% of pts with ER+/HER2- eBC develop resistance (in some cases due to the acquisition of tumor mutations in ESR1 that can drive estrogen-independent transcription and proliferation) and still have high recurrence rates on standard ETs. New treatment alternatives for ER+/HER2- eBC are needed to reduce risk of recurrence and improve survival, tolerability, quality of life, and adherence. Giredestrant is a highly potent, nonsteroidal oral selective ER antagonist and degrader (SERD). It achieves robust ER occupancy and is active against tumors that retain ER-sensitivity or have ESR1 mutation(s). Giredestrant has been demonstrated to be more potent in vitro and achieves higher ER occupancy in vivo than fulvestrant, the only currently approved SERD. Early phase clinical studies have demonstrated that single-agent giredestrant (30 mg daily) has promising clinical and pharmacodynamic activity, and is well-tolerated in the ER+/HER2- eBC and metastatic BC settings. TRIAL DESIGN This is a phase III, global, randomized, open-label, multicenter study evaluating the efficacy and safety of adjuvant giredestrant vs physician’s choice of adjuvant ET in pts with medium- and high-risk stage I-III histologically confirmed ER+/HER2- eBC. Pts are randomized 1:1 to oral 30 mg daily giredestrant or physician’s choice of standard ET (tamoxifen, anastrozole, letrozole, or exemestane, given according to prescribing information). Stratification factors are risk (medium vs high, based on anatomic [tumor size, nodal status] and biologic features [grade, Ki67, gene signatures if available]); geographic region (US/Canada/Western Europe vs Asia-Pacific vs rest of the world); prior chemotherapy (no vs yes); and menopausal status (pre-/perimenopausal vs postmenopausal). Beginning on Day 1 of Cycle 1, pts will be treated with giredestrant or physician’s choice of standard ET for at least 5 years. Continuing physician’s choice of standard ET after 5 years is at discretion of the investigator and per local standard of care. ELIGIBILITY Female/male pts with medium-/high-risk stage I-III ER+/HER2- eBC; prior curative surgery; completion of (neo)adjuvant chemotherapy (if administered) and/or surgery &amp;lt;12 months prior to enrolment; no prior ET (up to 4 weeks of [neo]adjuvant ET is allowed). For men and pre-/perimenopausal women, a luteinizing hormone-releasing hormone agonist will be given per local prescribing information (mandatory for pts in the giredestrant arm). AIMS Primary endpoint: Invasive disease-free survival (IDFS). Secondary endpoints: Overall survival; IDFS (STEEP definition, including second non-primary BC); disease-free survival; distant recurrence-free survival; locoregional recurrence-free interval; safety; pharmacokinetics; pt-reported outcomes. In addition, this study aims to improve health equity in research and expand clinical trial access. The study will also use/develop digital healthcare solutions, which will enable better understanding of patients’ needs and their adherence to ET. STATISTICAL METHODS The primary endpoint analysis will use a stratified log-rank test at an overall 0.05 significance level (two-sided). An interim analysis and a futility analysis are planned, and an independent data monitoring committee will be in place. ACCRUAL Target enrollment is 4100 pts globally once the study is open for enrollment. CONTACT INFORMATION For more information or to refer a patient, email global.rochegenentechtrials@roche.com or call 1-888-662-6728 (USA only). Clinicaltrials.gov number NCT04961996. Citation Format: Aditya Bardia, Peter Schmid, Nadia Harbeck, Mothaffar F Rimawi, Sara A Hurvitz, Sherene Loi, Shigehira Saji, Kyung Hae Jung, Gustavo Werutsky, Daniil Stroyakovskii, Vanesa López-Valverde, David Tesarowski, Chenglin Ye, Michael Davis, Tanja Badovinac Crnjevic, Pablo Diego Perez-Moreno, Charles E Geyer, Jr. Lidera breast cancer: A phase III adjuvant study of giredestrant (GDC-9545) vs physician’s choice of endocrine therapy (ET) in patients (pts) with estrogen receptor-positive, HER2-negative early breast cancer (ER+/HER2- EBC) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT2-11-09.

Importance of tumor size in resectable stage III-N2 non–small cell lung cancer

ObjectiveThe 8th TNM edition classifies stage III-N2 disease as IIIA and IIIB based on a tumor size cutoff of 5 cm. However, the importance of tumor size on survival in patients with resectable stage III-N2 disease has not been analyzed systematically. MethodsSurvival analysis based on tumor size (>5 cm vs ≤ 5 cm) for 255 consecutive patients with nonbulky (maximal lymph node diameter of 1.5 cm) stage III-N2 non–small cell lung cancer treated with surgery in our institution. ResultsNinety patients (35.3%) underwent induction chemoradiation therapy (n = 72, 28%) or induction chemotherapy (n = 18, 7%), and 165 patients underwent primary surgery followed by adjuvant chemotherapy (n = 52, 32%), adjuvant chemoradiation therapy (n = 47, 29%), or adjuvant radiation therapy (n = 14, 13.2%). After a median follow-up of 6.5 years, the overall survival was 46.5% at 5 years and 28.9% at 10 years. In tumors 5 cm or less, there was no difference in survival between patients treated with induction or adjuvant therapy. However, in tumors greater than 5 cm, the survival was significantly better after induction therapy compared with adjuvant therapy or surgery alone. Pathologic multi-station N2 disease was more frequently detected in tumors greater than 5 cm (31% vs 18% in tumors ≤5 cm, P = .042), and the rate of R1 resection was lower after induction therapy (2.2% vs 8.5% in primary surgery, P = .048). ConclusionsThese results support the redefinition of tumors greater than 5 cm with resectable N2 disease to stage IIIB. This change should help to refine the multimodality approach for stage III-N2 lung cancer.

Microenvironment-driven intratumoral heterogeneity in head and neck cancers: clinical challenges and opportunities for precision medicine.

Squamous cell carcinoma of the head and neck (SCCHN) is among the most prevalent cancer types worldwide. Despite multimodal therapeutic approaches that include surgical resection, radiation therapy or concurrent chemoradiation, targeted therapy and immunotherapy, SCCHN is still associated with a poor prognosis for patients with locally advanced or recurrent/metastatic (R/M) diseases. Although next-generation sequencing data from thousands of SCCHN patients have provided a comprehensive landscape of the somatic genomic alterations in this disease, genomic-based precision medicine is not implemented yet in routine clinical use since no satisfactory genetic biomarker has been identified for diagnosis, patient outcome prediction and selection of tailored therapeutic options. The lack of significant improvement in SCCHN patient survival over the last decades stresses the need for reliable predictive biomarkers and new therapeutic strategies for personalized clinical management of SCCHN patients. Targeting the SCCHN-associated microenvironment or the interaction of the latter with cancer cells may represent such paradigm shift in the development of new strategies to treat SCCHN patients, as exemplified by the recent implementation of immune checkpoint inhibitors to improve clinical outcomes by increasing anti-tumor immune responses in SCCHN patients. Several clinical trials are in progress in SCCHN patients to evaluate the activity of monoclonal antibodies and small-molecule inhibitors targeting the tumor microenvironment (TME) at different treatment settings, including combinations with adjuvant surgery, radiation therapy and chemotherapy. This review describes the current knowledge about the influence of the TME on intratumoral heterogeneity and clinical relapse in human SCCHN patients. More precisely, the role of hypoxia as well as the presence of non-cancer cells (e.g. cancer-associated fibroblasts and immune cells) on therapy response of SCCHN cells is highlighted. We also discuss relevant (pre)clinical models that may help integrate the microenvironment-tumor cell interplay in translational research studies for SCCHN. Finally, this review explores potential therapeutic strategies that may exploit the crosstalk between TME and SCCHN cells in order to implement fundamental changes in the tumor treatment paradigm of patients with locally advanced or R/M SCCHN.

The current state of pathology and immunohistochemistry in gestational trophoblastic disease therapeutic management: A tertiary center experience

Gestational trophoblastic disease (GTD) is derived from the abnormal development of trophoblastic tissue and covers a broad range of benign and malignant disorders. The histological diagnosis of GTD continues to be a challenge, even among expert pathologists. The present study evaluates the roles of pathology and immunohistochemistry in GTD diagnostic and therapeutic approaches. A retrospective study was conducted in Filantropia Clinical Hospital, Bucharest, Romania, involving cases of GTD between 2010 and 2020. We reported 19 clinically diagnosed and histologically confirmed cases of GTD, 15 moles (complete and partial), along with 4 cases of gestational trophoblastic neoplasia (GTN). The mean age of the patients studied was 31.3±7.5 years. The percentage of cases diagnosed after the sonographic evaluation was 94.7%. The rate of progression of GTD to GTN was 5.2%. Seven patients with low-risk GTD (risk score six or less) were treated with first-line chemotherapy (CT), and two cases required second-line CT. Twelve patients with highrisk GTD (risk score seven or more) were treated with first-line CT (n = 4), first-line CT followed by second-line CT (n = 4), first-line CT with adjuvant surgery (n = 3), and first-line surgery (one case). No causal relationship has been established between the forms of gestational trophoblastic disease regarding hCG level, the rate of normalization of hCG, and the rate of progression to GTN. After chemotherapy for GTD, only 42.1% of patients who wanted a future pregnancy could conceive. Underutilized in the current practice (5.2%), the immunohistochemical markers for trophoblasts and DNA genotyping are particularly useful tools in the fast and accurate diagnosis and prognosis of GTD.

Promotion of angiogenesis toward transplanted ovaries using nitric oxide releasing nanoparticles in fibrin hydrogel

Transplantation of ovary is one method of facilitating fertility preservation to increase the quality of life of cancer survivors. Immediately after transplantation, ovaries are under ischemic conditions owing to a lack of vascular anastomosis between the graft and host tissues. The transplanted ovaries can suffer damage because of lack of oxygen and nutrients, resulting in necrosis and dysfunction. In the technique proposed in this paper, the ovary is encapsulated with nitric oxide-releasing nanoparticles (NO-NPs) in fibrin hydrogels, which form a carrying matrix to prevent ischemic damage and accelerate angiogenesis. The low concentration of NO released from mPEG-PLGA nanoparticles elicits blood vessel formation, which allows transplanted ovaries in the subcutis to recover from the ischemic period. In experiments with mice, the NO-NPs/fibrin hydrogel improved the total number and quality of ovarian follicles after transplantation. The intra-ovarian vascular density was 4.78 folds higher for the NO-NPs/fibrin hydrogel groups compared to that for the nontreated groups. Finally, in vitro fertilization revealed a successful blastocyst formation rate for NO-NPs/fibrin hydrogel coated ovaries. Thus, NO-NPs/fibrin hydrogels can provide an appropriate milieu to promote angiogenesis and be considered as adjuvant surgery materials for fertility preservation.

P-P23 Adjuvant chemotherapy in the treatment of intraductal papillary mucinous neoplasms of the pancreas: systematic review and meta-analysis

Abstract Background The present systematic review aimed to compare survival outcomes of invasive intraductal papillary mucinous neoplasms (IIPMNs) treated with adjuvant chemotherapy versus surgery alone and to identify pathologic features that may predict survival benefit from adjuvant chemotherapy. Methods A systematic search of Medline, Pubmed, Scopus, and EMBASE was performed using the PRISMA framework. Studies comparing adjuvant chemotherapy and surgery alone for patients with IIPMNs were included. Primary endpoint was overall survival (OS). A narrative synthesis was performed to identify pathologic features that predicted survival benefits from adjuvant chemotherapy. Results Eleven studies and 3393 patients with IIPMNs were included in the meta-analysis. Adjuvant chemotherapy significantly reduced risk of death in the overall cohort (HR 0.57, 95%-CI:0.38-0.87, p = 0.009) and node-positive patients (HR 0.29, 95%-CI:0.13-0.64, p = 0.002). Weighted median survival difference between adjuvant chemotherapy and surgery alone in node-positive patients was 11.6 months (95%-CI:3.83-19.38, p = 0.003) favouring chemotherapy. Adjuvant chemotherapy had no impact on OS in node-negative patients (HR 0.53, 95%-CI:0.20-1.43, p = 0.209). High heterogeneity (I2&amp;gt;75%) was observed in pooled estimates of hazard ratios. Improved OS following adjuvant chemotherapy were reported for patients with stage III/IV disease, tumour size &amp;gt;2 cm, node-positive status, grade 3 tumour differentiation, positive margin status, tubular carcinoma subtype, and presence of perineural or lymphovascular invasion. Conclusions Adjuvant chemotherapy was associated with improved OS in node-positive IIPMNs. However, the findings were limited by marked heterogeneity. Future large multicentre prospective studies are needed to confirm these findings and explore additional predictors of improved OS to guide patient selection for adjuvant chemotherapy.