Postoperative Chemoradiotherapy Research Articles

Extensive clinical target volume in postoperative chemoradiotherapy for esophageal squamous cell carcinoma: a phase II clinical trial (ESO-Shanghai 9)

BackgroundTo compare the efficacy and safety of postoperative extensive target volume irradiation with elevated radiation dose and concurrent chemotherapy with radiotherapy only for the postoperative treatment of esophageal squamous cell carcinoma.MethodsThis trial was a single-arm phase II trial. Patients who underwent a radical transthoracic resection with negative margins within 3 months and histologically confirmed esophageal squamous cell carcinoma (pT3-4N0M0 or pTxN + M0, AJCC 7th) were eligible for this study. Postoperative radiotherapy was performed at a total dose of 45 Gy in 25 fractions with clinical target volumes of the tumor bed, anastomosis, bilateral supraclavicular, mediastinal, left gastric and celiac trunk lymph node areas. Five cycles of weekly TC (paclitaxel 50 mg/m2, d1, carboplatin AUC = 2, d1) were given as concurrent chemotherapy. The primary endpoint was the 2-year local control rate, and the secondary endpoints were overall survival, disease free survival, local-regional recurrence free survival, distant metastasis free survival and adverse events. All endpoints were compared with those in ESO-Shanghai 8 study with postoperative radiotherapy alone (40 Gy/20Fx).ResultsA total of 70 patients were enrolled from 2016 to 2018. The 2-year local control rate was 87.9% (95% CI: 83.3–92.3) in this study, which achieved the hypothesized 2-year local control rate of at least 83%. Overall survival, disease free survival, local-regional recurrence free survival and distant metastasis free survival in this study were also longer than those in previous ESO-Shanghai 8 study while most toxicities were increased and two patients in this study died of radiation pneumonitis.ConclusionsPostoperative extensive target volume irradiation with elevated radiation dose and concurrent chemotherapy was effective. Treatment related toxicity was increased due to higher treatment intensity.Trial registration clinicaltrials.gov: NCT02916511.

Intraoperative Assessment of Surgical Margins in Cancer Resection Surgery Via the Sub-Diffuse Optical Tomography "S-DOT"

In Head and Neck Squamous Cell Carcinomas (HNSCC), positive margins after surgical resection dominate the clinical outcome of patients. Between 15-30 precent of all HNSCC surgeries result in a positive margin (>5mm) that requires postoperative chemo-radiation, radiotherapy, and/or revision surgeries. To minimize local recurrence, margin assessment is typically performed through surgical pathology departments; however, this technique often takes more than 24 hours to process and only a small fraction of the total surgical margin is evaluated. A second, intraoperativeapproach used by surgeons to minimize local recurrence is frozen section analysis (FSA), which in time intensive and suffers heavily from sampling errors. To effect change, we have hypothesized a sub-diffuse optical tomography modality that can identify the differences in depth sensitivity of the fluorescence, Cetuximab-IRDye800CW conjugate (ICON), by the fluorescent photons collected from sub-diffused media as a function of the photon exit angle from the excited tissue. Based on promising preliminary simulations using Monte Carlo MATLAB, closed vs. open aperture fluorescence imaging in biological tissue demonstrated an enhanced true depth of fluorescence resolution up to 6mm, well beyond the insufficient 5mm mark. By identifying the deep margins from the fluorescent peaks within 5 minutes, we hope to improve complete oncological surgery by providing surgeons an exact region of interest on the specimen where the tumor is closest to the edge, so they may continue surgery by providing sugeons an exact region of interest on the specimen where the tumor is closest to the edge, so they may continue surgery on the spot to minimize the probability of cancer being left behind.

Time to first treatment and optimal adjuvant treatment strategy in patients with resectable gastric cancer pathologically upstaged to lymph node–positive disease.

473 Background: Treatment strategies in resectable gastric cancer (GC) patients include perioperative chemotherapy (PEC), postoperative chemoradiation therapy (POCR), and postoperative chemotherapy (POC). Treatment delay can lead to metastases with unfavorable outcomes. We aim to identify the distribution of patients upstaged to pathologically node positive disease (pLN+) stratified by time and the optimal treatment in this cohort. Methods: We analyzed resected GC patients in the National Cancer Database (2004-2016) with clinically node negative disease (cLN-). Time from diagnosis to first definitive therapy was stratified as ≤2, >2 to ≤4, and >4 weeks. The distribution of patients upstaged from cLN- to pLN+ disease, the concordance between cLN- and pathologically lymph node negative (pLN-) disease based on treatment strategy, and time to first definitive therapy was analyzed. POC and POCR were compared to evaluate their effect on overall survival (OS) in patients with cLN- upstaged to pLN+ disease. Kaplan-Meier test, log-rank test, multivariable Cox proportional hazards analysis (MVA) were performed. Results: Of the 4,828 gastric cancer patients with cLN- disease, 514 (10.65%) patients received PEC and 4,314 (89.35%) patients received upfront surgery followed by POCR/POC. Distribution of patients stratified by time between diagnosis to first definitive treatment - chemotherapy (PEC) or surgery (POC/POCR), for ≤2 weeks was 9.5% vs. 33%, >2 - ≤4 weeks was 28.4% vs. 24.2% and >4weeks was 62% vs 42.7%, respectively. Patients upstaged from cLN- to pLN+ disease in the PEC group was 43.37%(n=206), and 70%(n=2574) in the upfront surgery group (POC/POCR). Of the 206 (43.37%) patients upstaged from cLN- to pLN+ in the PEC cohort, the upstage rate was 7.77% when chemotherapy was started within 2 weeks of diagnosis, compared to 27.67% with >2 to ≤4 weeks, and 64.56% with >4 weeks. Of the 2,574 (70%) patients upstaged in the upfront surgery cohort (POCR/POC), 30.61% were upstaged in ≤2 weeks, 24.95% in >2 to ≤4 weeks, and 44.44% in ≥4 weeks. On MVA, patients with cLN- disease that were pLN- (POCR=766, POC=341) had no significant difference in OS when treated with POCR (HR 1.11, p=0.39) compared to POC. Patients with pLN+ (POCR=2300, POC=907) disease had an association with improved OS when treated with POCR (HR 0.78, p<0.001) compared to POC. Conclusions: When resectable gastric cancer patients undergoing upfront surgery are upstaged from clinically node negative to pathologically node positive disease, postoperative chemoradiation therapy may be the optimal treatment strategy compared to postoperative chemotherapy. Clinical nodal status may not be an optimal predictor of nodal disease.

A phase II study to evaluate anlotinib plus TQB2450 as adjuvant therapy in patients with esophageal squamous cell carcinoma (ALTER-E005).

TPS488 Background: About 30.3-58.0% of patients who undergo esophagectomy may experience recurrence. The efficacy of postoperative chemoradiation has not been demonstrated in a randomized trial in patients with esophageal squamous cell carcinoma (ESCC) compared to surgery along. Therefore, it is urgent to explore more effective and safer postoperative regimen for resectable ESCC. Checkmate 577 has demonstrated immunotherapy can prolong disease free survival (DFS) for patients who have residual disease following preoperative chemoradiation and R0 resection. Anlotinib is an orally administered tyrosine kinase inhibitor that targets VEGFR1-3, FGFR1-4 and PDGFRα/β. In a randomized, double-blind phase 2 trial, the use of anlotinib in previously treated metastatic ESCC patients significantly improved progression-free survival (PFS) compared with placebo ( NCT02649361 ). TQB2450 is a novel humanized monoclonal antibody against PD-L1, which has shown encouraging activity in combination with anlotinib in the treatment of multiple tumors, such as biliary tract cancer (NCT03996408) and ovarian cancer (NCT04236362). The ALTER-E005 study is designed to evaluate the efficacy and safety of anlotinib combined with TQB2450as adjuvant therapy in ESCC patients. Methods: ALTER-E005 is a multi-center, single-arm, phase II study. A total of 30 patients will be enrolled. Eligible pts (≥18 years) must be histologically confirmed T1-2N1-3M0 or T3-4NanyM0 ESCC; received radical (R0) resection of ESCC with no recurrence in imaging examination within 6-12 weeks after surgery; ECOG PS 0–1. Patients enrolled will receive oral anlotinib 12 mg on days 1-14 and intravenous TQB2450 1,200 mg on day 1 every 3 weeks until disease recurrence. The primary endpoint is DFS. The secondary endpoints include safety, 1-year DFS rate, 3-year DFS rate, 1-year overall survival (OS) rate, and 3-year OS rate. Enrollment to the ALTER-E005 trial is currently ongoing in China. Clinical trial information: NCT05252078 .

Prognostic Value of Controlling Nutritional Status Score in Advanced Hypopharyngeal Cancer.

The purpose of this study was to investigate the prognostic significance of the preoperative controlling nutritional status (CONUT) score in patients with resectable advanced hypopharyngeal cancer. This retrospective study included 113 advanced hypopharyngeal cancer patients who underwent curative resection in our hospital from 2013 to 2017. The association between the CONUT score and clinicopathological variables was evaluated. The association between CONUT score and survival was analyzed using Kaplan-Meier survival curves and Cox regression. The efficacy of the CONUT score and other immune-nutritional markers to predict prognosis was compared using a time-dependent receiver operating characteristic (ROC). Patients were divided into the high-CONUT score group (≥3) and the low-CONUT score group (≤2) according to ROC analysis. The CONUT score was associated with body mass index (p=0.047), monocyte (p=0.021), pharyngocutaneous fistula (p=0.045), flap repairment (p=0.034), tumor (T) classification (p=0.034), node (N) classification (p=0.036), subsite of tumor (p=0.035), and negative pathologic factors (p < 0.001). Tumor, node, metastasis (TNM) stage, negative pathologic factors, adjuvant radiotherapy, postoperative chemoradiotherapy, and CONUT score were independent prognostic factors for survival. Patients with a higher CONUT score had worse overall survival (OS) (hazard ratio: 2.76, 95% confidence interval [CI]: 1.44-5.29, p=0.002) and disease-free survival (hazard ratio: 2.51, 95% CI: 1.28-4.91, p=0.007). The area under the curve of the CONUT score (0.799) to predict 5-year OS wasgreater than those of Preoperative Nutritional Index (0.769), platelet-to-lymphocyte ratio (0.643), neutrophil-to-lymphocyte ratio (0.565), and lymphocyte-to-monocyte ratio (0.577). The CONUT score is a prognostic marker for patients with resectable advanced hypopharyngeal cancer. 3 Laryngoscope, 133:2613-2620, 2023.

PREVLAR: Phase 2a Randomized Trial to Assess the Safety and Efficacy of RRx-001 in the Attenuation of Oral Mucositis in Patients Receiving Head and Neck Chemoradiotherapy

No Food and Drug Administration-approved intervention exists for oral mucositis (OM) from chemoradiotherapy (CRT) used to treat head and neck cancers. RRx-001 is a hypoxia-activated, cysteine-directed molecule that affects key pathways involved in OM pathogenesis. This phase 2a, multi-institutional trial was designed to assess the safety and feasibility of 3 schedules of a fixed concentration of RRx-001; a standard-of-care arm was included to identify potential signals of efficacy for further study. This study enrolled patients with oral cavity and oropharynx squamous cell carcinoma receiving definitive or postoperative cisplatin-based CRT. Patients were randomized into 4 cohorts. In arms 1 to 3, RRx-001 was coinfused with patients' blood at differing intervals. Arm 4 was a control cohort of patients treated with CRT alone. Trained evaluators assessed OM using a standardized data collection instrument twice weekly during treatment and then until resolution. OM severity was scored centrally using World Health Organization criteria. Safety outcomes were assessed using National Cancer Institute - Common Terminology Criteriav4 benchmarks. Long-term tumor response was defined by Response evaluation criteria in solid tumors v1.1 criteria. Fifty-three patients were enrolled, with 46 and 45 individuals contributing safety and efficacy data, respectively. There were no severe adverse events attributed to the study drug. Across all 3 active arms, the study drug was infused fully per protocol in 86% of patients. All 3 RRx-001 treatment cohorts appeared to demonstrate a similar or lower OM duration relative to control; arm 1 had the lowest median duration of severe oral mucositis (SOM), 8.5 days versus 24 days in controls among patients who developed at least 1 day of SOM. There were no locoregional failures in any patient. Our results support the safety and feasibility of RRx-001 as an intervention to mitigate SOM. Additional studies are planned to confirm its efficacy.

Key Clinical Principles in the Management of Glioblastoma.

Glioblastoma is the most common and aggressive primary brain tumor in the adult population and leads to considerable morbidity and mortality. It has a dismal prognosis with average survival of 15-18 months, and the current standard-of-care treatment paradigm includes maximal surgical resection and postoperative concurrent chemoradiotherapy and maintenance chemotherapy, with consideration of Tumor Treating Fields. There is a major emphasis to enroll patients onto ongoing clinical trials to further improve treatment outcomes, given the aggressive nature of the disease course and poor patient survival. Recent research efforts have focused on radiotherapy dose intensification, regulation of the tumor microenvironment, and exploration of immunotherapeutic approaches to overcome the barriers to treatment. This review article outlines the current evidence-based management principles as well as reviews recent clinical trial data and ongoing clinical studies evaluating novel therapeutic options.

Relationship between postoperative nodal skip metastasis of mid-thoracic esophageal squamous cell carcinoma and patient prognosis and its value in guiding postoperative adjuvant treatment.

To evaluate the predictive role of nodal skip metastasis (NSM) in the prognosis of lymph node-positive mid-thoracic esophageal squamous cell carcinoma, and to evaluate the significance of postoperative adjuvant treatment in patients with different sites of metastatic nodes. A retrospective analysis was performed on clinical data of 321 lymph node-positive mid-thoracic esophageal squamous cell carcinoma patients who underwent surgery in the Fourth Hospital of Hebei Medical University. Based on the site and condition of lymph node metastasis by postoperative pathology, the patients were divided into two groups: NSM group and non-NSM (NNSM) group. The propensity score matching (PSM) method was employed to match the two groups. The prognostic factors of patients before and after PSM as well as the effect of different adjuvant treatment modes on the prognosis of patients before and after PSM were analyzed. SPSS 29.0 statistical software was used for analysis. PSM in a 1 : 1 matching ratio was performed, 103 patients were assigned to NSM group and NNSM group respectively. Significant differences were found in the 3- and 5-year OS and DFS between the two groups before PSM, the 3- and 5-year OS also showed a significant difference after PSM (P < 0.05). Multivariate analysis illustrated that gender, postoperative adjuvant treatment mode, N stage and lymph node metastasis were independent risk factors for OS and DFS after PSM (P < 0.05); for NSM patients, postoperative adjuvant chemotherapy and radiotherapy significantly prolonged OS and DFS before and after PSM (P < 0.05). But no significant difference was found in OS and DFS for NNSM patients after PSM (P > 0.05). Postoperative NSM is a good prognostic factor for patients with mid-thoracic esophageal squamous cell carcinoma, postoperative adjuvant chemoradiotherapy was recommended for those group, thereby gaining survival benefits.

Retracted: Postoperative Adjuvant Chemoradiotherapy on the Survival of Stage III Gastric Cancer.

[This retracts the article DOI: 10.1155/2022/8036763.].

A Case of Pharyngo-esophageal Obstruction After Postoperative Chemoradiotherapy for Oropharyngeal Carcinoma Which Was Resolved by Transoral and Transgastrostomy Endoscopy

A Case of Pharyngo-esophageal Obstruction After Postoperative Chemoradiotherapy for Oropharyngeal Carcinoma Which Was Resolved by Transoral and Transgastrostomy Endoscopy

The effect of radiotherapy time and dose on acute hematologic toxicity during concurrent postoperative chemoradiotherapy for early high-risk cervical cancer.

Objective: This study aims to analyze the characteristics and factors that influence acute hematological toxicity (HT) during concurrent chemoradiotherapy (CCRT) for cervical cancer, as well as to provide reference data for clinical practice. Methods: Patients with FIGO IB1-IIA2 cervical cancer who underwent CCRT from May 2018 to August 2020 were included in this study retrospectively. All patients had received external beam radiation therapy and platinum-based concurrent chemotherapy. HT was assessed according to CTCAE 5.0. The pelvic bone marrow was redrawn on the original CT images and divided into four parts: the whole pelvic bone marrow (WP-BM), iliac bone marrow (IL-BM), lower pelvic bone marrow (LP-BM), and lumbosacral bone marrow (LS-BM). The radiation dose and volume of each part of the pelvic bone marrow were recalculated in a new plan created using the original planning parameters. The corresponding dose-volume histogram (DVH) was generated to obtain the bone marrow volumes receiving 10Gy, 20Gy, 30Gy, 40Gy, 45Gy, and 50Gy. Results: In 112 patients, the incidences of grade 2 or higher leukopenia, anemia, thrombocytopenia, and neutropenia were 49.1%, 2.7%, 1.8%, and 20.5%, respectively. Leukopenia was linked to LS-V20 (r = -0.310; P = 0.006) and radiotherapy treatment lengths (days) (r = -0.416; P = 0.013). Anemia was associated with WP-V30, WP-V40, WP-V45, WP-V50, IL-V20, IL-V40, ILV45, IL-V50, LP-V30, LP-V40, LP-V45, and LP-V50 (P <0.05). Thrombocytopenia (r = -0.304, P = 0.007) and neutropenia (r = -0.368, P = 0.009) was associated only with the length of radiotherapy treatment (day). Multiple regression analysis showed that only anemia was negatively correlated with WP-V30, IL-V40, and LP-V40 (P <0.05). Conclusions: Acute HT during CCRT in early-stage high-risk cervical cancer may be related to the duration of radiotherapy and the volume of different radiotherapy doses received at different parts in the pelvic bone marrow.

CLEAR CELL VARIANT OF SQUAMOUS CELL CARCINOMA PENIS – A CASE REPORT

Carcinoma penis is a rare malignancy in males. The World Health Organization Classification of Tumors of the Urinary System and Male Genital Organs classifies squamous cell carcinoma of the penis into human papillomavirus (HPV) and non HPV related. Among the HPV-related Squamous cell carcinomas of the penis, clear cell variant is a rare. Here we report a case of clear cell variant of squamous cell carcinoma of penis with bilateral inguinal lymph node metastasis. We have treated this patient with radical surgery, wide excision and bilateral inguinal lymph node dissection followed by post operative chemo radiation. But during radiation itself the disease progressed, with rapid recurrence of inguinal lymph node metastasis, finally end up with palliative chemotherapy. Clear cell carcinoma is an aggressive form of cancer, with frequent metastasis to the inguinal lymph nodes, as seen in this case. Immunohistochemistry examination P16 was absent. So it is considered as clear cell variant of squamous cell carcinoma. Clinical experience with penile carcinoma is limited because of their rarity.

NQPC-9 CHARACTERIZATION AND MANAGEMENT OF DERMATOLOGIC ADVERSE EVENTS WITH OPTUNE® IN WAKAYAMA MEDICAL UNIVERSITY HOSPITAL

Abstract Introduction The NovoTTF-100A System (NovoTTF™ Therapy, Optune®, Novocure Inc.) is approved for use as a combination therapy with adjuvant temozolomide after postoperative chemo-radiation for newly diagnosed supratentorial glioblastoma (GBM). In our experience, dermatologic adverse events (dAEs) due to the continuous contact between the array and the scalp is not infrequently occurred, and we believe that the addition of skincare strategy is vital to maximize adherence to the NovoTTF™ Therapy. In Wakayama Medical University Hospital (WMUH), “WOC nurses,” certified Nurses in Wound, Ostomy and Continence Nursing, cooperate with neurosurgeons for the skincare of the patients.In this presentation, we review our dAE experience and introduce our skincare strategy by WOC nurse. Methods We collected and analyzed clinical information of GBM patients treated with NovoTTF™ Therapy in WHUH and focused on the dAEs of the patients. Results Total 7 patients (Male, 6; Female, 1). Median age, 64.4 (38-78). dAEs occurred in 6/7 cases (86%). dAEs includes contact dermatitis 5 (71%), erosion 3 (43%), ulcers 0, foliiculitis 3 (43%). CTCAE grading of dAEs, 1 or 2. Two cases (29%) abandoned NovoTTF™ Therapy due to dAEs. Based on our skincare strategy, which consists of three essential rules of scalp care (cleansing, moisturization, protection), WOC nurses have close contact with the patients and their caregivers from the beginning of the therapy. Conclusion The addition of skincare strategies to the NovoTTF-100A System would be vital for the adherence to NovoTTF therapy, which contribute to the therapeutic benefit of the Therapy. Not only neurosurgeons and patients but also nurses and caregivers must cooperate in scalp care and dAE treatment.

The efficacy of postoperative radiotherapy for patients with non-small cell lung cancer: An updated systematic review and meta-analysis.

The controversy over the efficacy of postoperative radiotherapy (PORT) has existed for a long time. The present study reassessed the overall survival (OS) and disease-free survival (DFS) data to investigate whether PORT can improve survival in resectable non-small cell lung cancer (NSCLC) patients. The following databases were used to perform literature search: PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), and Embase (from January 1, 1986 to July 5, 2021). The results of overall survival (OS) and disease-free survival (DFS) were calculated as hazard ratio (HR). Confidence intervals are chosen with 95% confidence intervals. A total of 12 RCTs and 19 retrospective cohort studies were found to meet the inclusion criteria. A significant DFS improvement was detected in the PORT group (4111 patients from 15 studies), although statistical difference was not detected for OS between the non-PORT and PORT groups (31 studies, 49,342 total patients). PORT prolonged OS in patients undergoing PORT plus postoperative chemotherapy (POCT) and in pN2 patients. Patients with a median radiation dose of 50.4 Gy and a median radiation dose of 54 Gy had a better OS after PORT. However, if the total radiotherapy dose went up to 60 Gy, PORT increased the risk of death in NSCLC patients. Significant difference in OS was not found in the results of studies with regard to treatment methods, pathologic stages, study type, radiation beam quality, and radiation dose. Patients undergoing postoperative chemoradiotherapy and pN2 patients can benefit from PORT. Patients exposed to median radiation doses of 50.4 and 54 Gy demonstrated relatively good efficacy. For patients with non-small-cell lung cancer, PORT has not been proven to extend OS, but its effect on DFS remains strong.

Chemoradiotherapy for elderly patients with rectal cancer: A single-institution study.

The incidence of cancer, particularly rectal cancer (RC), in older adults is gradually increasing. The aim of the present study was to evaluate radiotherapy (RT) and chemoradiotherapy (CRT) results, clinicopathological features, and survival factors in older patients with RC. We evaluated patients aged ≥65 years with RC treated at a radiation oncology clinic. The demographic, clinical, and histopathological data of the patients were obtained by reviewing their medical records. The toxicity criteria of the Radiation Therapy Oncology Group were applied. Among 401 patients with RC, 183 (45.6%) were older adults (65-92 years). Furthermore, 122 (66.7%) patients had clinically stage 3 and above RC, and 183 and 91 patients received RT and neoadjuvant CRT, respectively. Surgical treatment was performed for 116 (63.4%) patients, 41 (34.4%) and 76 (65.6%) of whom underwent postoperative CRT and preoperative RT, respectively. Grade 3 or higher toxicity was observed in 22 (18.9%) patients during CRT. RT was performed in 64 patients (35%) at a 1-15-day interval. The mean follow-up duration was 34.7 (range, 1.4-149.0) months. The 2- and 5-year overall survival (OS) rates were 71.4 and 37.4%, respectively, and the 2- and 5-year disease-free survival (DFS) rates were 65.7 and 35.3%, respectively. OS was 49.4 and 34.9 months for patients aged 65-74 and ≥75 years, respectively. Survival was shorter in patients with the advanced geriatric disease (p = 0.013). In the multivariate analysis, factors affecting overall and DFS were age, distance from the tumor to the anal canal, and metastasis (p < 0.05). The results of this study suggested that the selection of treatment modalities for older patients with RC should be based on performance status and not age. RT and CRT were safe treatment modalities for older patients with RC, particularly for those who could not undergo surgery.

The impacts of minimally invasive surgery on intermediate- or high-risk cervical cancer patients received adjuvant radiotherapy

BackgroundAdjuvant chemoradiotherapy (CRT) has been shown to reduce the risk of recurrence for patients with risk factors after radical hysterectomy (RH). Early initiated CRT could result in superior oncological outcomes. Here, we aimed to compare the survival outcome of intermediate- or high-risk cervical cancer (CC) patients who, received adjuvant CRT between minimally invasive surgery (MIS) and open surgery.MethodsData on stage IB1-IIA2 patients who underwent RH and postoperative CRT in our institution, from 2014 to 2017, were retrospectively collected. Patients with high or intermediate-risk factors who met the Sedlis criteria received sequential chemoradiation (SCRT). According to the surgical approaches, the enrolled patients were divided into MIS and open surgery groups. Then, the disease-free survival (DFS), overall survival (OS), and prognostic factors were analyzed.ResultsAmong 129 enrolled CC patients, 68 received open surgery and 61 received MIS. The median time interval from surgery to chemotherapy and to radiotherapy was shorter in the MIS group (7 days vs. 8 days, P=0.014; 28 days vs. 35, P<0.001). Three-year DFS and OS were similar in both groups (85.2% vs. 89.7%, P=0.274; 89.9% vs. 98.5%, P=0.499). Further, sub-analysis indicated that the DFS and OS in intermediate/high-risk groups had no significant difference. Cox-multivariate analyses found that tumor size >4 cm and time interval from surgery to radiotherapy beyond 7 weeks were adverse independent prognostic factors for DFS.ConclusionBased on the population we studied, for early-stage (IB1-IIA2) CC patients with intermediate- or high-risk factors who received postoperative SCRT, although the difference was not significant, the DFS and OS in the MIS group were slightly lower than the ORH group, and tumor size >4 cm and delayed adjuvant radiotherapy beyond 7 weeks were risk factors for recurrence.

Diagnostic performance of perfusion-weighted imaging combined with serum MMP-2 and -9 levels in tumor recurrence after postoperative concomitant chemoradiotherapy of glioblastoma.

To evaluate diagnostic accuracy of dynamic susceptibility contrast- perfusion weighted imaging (DSC-PWI) combined with serum MMP-2 and -9 levels in differentiating recurrent glioblastoma (GBM). We enrolled a total of 220 GBM patients, including recurrent cases (n=150) and non-recurrent cases (n=70) after postoperative concomitant chemoradiotherapy. All patients performed preoperative and follow-up DSC-PWI, and two parameters [normalized cerebral blood volume (nCBV) and cerebral blood flow (nCBF)] were obtained. Preoperative serum levels of MMP-2 and MMP-9 were detected using ELISA. The diagnostic performance was evaluated by analyzing receiver operating characteristic (ROC) and area under the curve (AUC). At baseline, the recurrence patients had higher nCBF and nCBV than the non-recurrence patients, accompanying by the increased MMP-2 and MMP-9 levels in serum. Serum MMP-2 level were positively associated with MMP-9 in recurrent patients. In patients classified as recurrence, both MMP-9 and MMP-2 in serum had a significant correlation with nCBV and nCBF. A sensitivity and specificity of nCBF for recurrence vs. non-recurrence were 94.29% and 63.33%, respectively. nCBV also could provide high discrimination between recurrence and non-recurrence patients (sensitivity: 84.29%, specificity: 62.67%, AUC: 0.821). In ROC analyses, both MMP-2 and MMP-9 distinguished recurrence from non-recurrence with AUC values of 0.883 and 0.900, respectively. Finally, the combination of DSC-PWI parameters (nCBF and nCBV) and serum MMP-2 and -9 levels showed much better discrimination capacity between recurrence and non-recurrence patients with a sensitivity of 92.86%, specificity of 79.33% and AUC of 0.899. The combination of DSC-PWI parameters together with serum MMP-2 and -9 levels offered an attractive approach to noninvasively distinguish recurrence after postoperative radiotherapy of GBM.

The effectiveness of consolidation chemotherapy in high-risk early-stage cervical cancer patients following concurrent chemoradiation after radical surgery.

Studies determining which early-stage cervical cancer patients with high-risk factors benefit from consolidation chemotherapy after postoperative concurrent chemoradiotherapy (CCRT) are limited and inconsistent. The aim of this study was to evaluate the value of consolidation chemotherapy in early-stage cervical cancer. From 2010 to 2019, a retrospective review was conducted among high-risk early-stage cervical cancer patients who were treated with postoperative CCRT or consolidation chemotherapy after postoperative CCRT. Disease-free survival (DFS) and overall survival (OS) were calculated using the Kaplan-Meier method and compared using the log-rank test. A total of 293 patients with early-stage cervical cancer were included in this study. A total of 188 patients were in the consolidation chemotherapy group, and 105 patients were in the postoperative CCRT alone group. The median follow-up was 48.3months (range: 3-123months). In the survival analyses, no significant differences in DFS (P=0.21) or OS (P=0.15) were observed between the groups. The grade 3-4 leukopenia and neutropenia rates in the consolidation group were higher than those in the concurrent chemoradiotherapy alone group (54.8% vs. 28.6%, P=0.02; 49.4% vs. 10.5%, P=0.001, respectively). For patients with ≥2 positive lymph nodes or ≥2 high-risk factors, consolidation chemotherapy significantly improved DFS (P=0.013 and P=0.002) and OS (P<0.001 and P<0.001) compared with CCRT alone. For early-stage cervical cancer, consolidation chemotherapy after postoperative CCRT improved survival outcomes in patients with ≥2 positive lymph nodes or ≥2 high-risk factors.

NIMG-40. RAPID EARLY PROGRESSION (REP) OF GLIOBLASTOMA IS AN INDEPENDENT NEGATIVE PROGNOSTIC FACTOR: RESULTS FROM A SYSTEMATIC REVIEW AND META-ANALYSIS

Abstract INTRODUCTION In patients with newly-diagnosed glioblastoma, rapid early progression (REP) refers to tumour regrowth between surgery and postoperative chemoradiotherapy. This systematic review and meta-analysis appraised published data on REP to better characterise and understand it. METHODS Systematic searches of MEDLINE, EMBASE and the Cochrane database from inception to 21/10/21. Studies describing the incidence of REP – tumour growth between the postoperative MRI scan and pre-radiotherapy MRI scan in newly-diagnosed glioblastoma, were included. The primary outcome was REP incidence. RESULTS From 1590 search results, 9 studies were included with 716 patients. The median age was 56.9 years (IQR 54.0-58.8 years). There was a male predominance with a median male-to-female ratio of 1.4 (IQR 1.1-1.5). The median number of days between MRI scans was 34 days (IQR 18-45 days). The mean incidence rate of REP was 45.9% (range 19.3%-72.0%) and significantly lower in studies employing functional imaging to define REP (p&amp;lt; 0.001). REP/non-REP groups were comparable with respect to age (p=0.99), gender (p=0.33) and time between scans (p=0.81). REP was associated with shortened overall survival (HR 1.78, 95% CI 1.30-2.43, p&amp;lt; 0.001), shortened progression-free survival (HR 1.78, 95% CI 1.30-2.43, p&amp;lt; 0.001), subtotal resection (OR 6.96, 95% CI 4-51-10.73, p&amp;lt; 0.001) and IDH wildtype versus mutant tumours (OR 0.20, 95% CI 0.02-0.38, p=0.03). MGMT promoter methylation was not associated with REP (OR 1.29, 95% CI 0.72-2.28, p=0.39). CONCLUSIONS REP occurs in almost half of patients with newly-diagnosed glioblastoma and has a strongly negative prognostic effect. Future studies should investigate its biology and effective treatment strategies.

CTNI-66. THE PREOPERATIVE BRAIN IRRADIATION IN GLIOBLASTOMA (POBIG) STUDY: A NOVEL TREATMENT PARADIGM TO IMPROVE OUTCOMES?

Abstract OBJECTIVE The Preoperative Brain Irradiation in Glioblastoma (POBIG) study evaluates for the first time the safety, feasibility, and impact of single fraction preoperative radiotherapy in newly diagnosed glioblastoma patients. METHODS Operable patients with a radiological diagnosis of glioblastoma, by consensus of a multidisciplinary tumor board including two dedicated neuro-radiologists, are screened for the study. Anatomical and functional MRI sequences are acquired for further tumor characterization and preoperative radiotherapy planning. Radiotherapy is delivered approximately two weeks after the initial screening. Radiation targets the macroscopic and microscopic tumor region at risk of being left behind during surgery and spares at least 2cc tumor volume being debulked to safeguard unperturbed and clinically relevant tissue examination and molecular profiling. The study dose-escalates (from 8Gy to 14Gy) based on the time-to-event Continual Reassessment Methodology. Subsequently, patients undergo surgical debulking followed by postoperative fractionated radiotherapy 60Gy/30fr with concurrent temozolomide. RESULTS The first POBIG study patient underwent preoperative radiotherapy followed by a subtotal resection of a left posterior fronto-opercular tumor and completed the postoperative chemoradiotherapy. Screening, study consent, MRI imaging and analysis, radiotherapy planning and delivery until surgery can be achieved within three weeks from screening while maintaining adequate and personalized patient communication. There were no surgical or radiotherapy delays or complications. During surgery, we successfully sampled unirradiated and irradiated tumor regions. The radiotherapy field covered the whole remnant tumor, and image-guided obtained tumor samples and imaging analysis showed clear evidence of differential radiation-induced changes. CONCLUSION We successfully initiated a new treatment strategy of preoperative radiotherapy for glioblastoma patients. The first patient completed the treatment, and the study is now open for further recruitment. Paired tumor sampling and advanced imaging analysis showed promising results. The POBIG study offers a unique opportunity for a paradigm shift towards personalized treatment regimens, hopefully leading to better outcomes.