Stage IIIB Patients Research Articles

Feasibility of neoadjuvant chemotherapy for bulky early stage to stage IIIB cervical cancer in Uganda

IntroductionExternal beam radiotherapy (EBRT) became unavailable in Uganda from February 2016 to November 2017. Following resource stratification guidelines, an alternative treatment strategy was developed. MethodsBulky early stage to Stage IIIB patients received at least 3 cycles of neoadjuvant chemotherapy (NAC). Surgery was performed if adequate response was achieved and adjuvant therapy given for high risk factors. Chemotherapy versus supportive care was advised in unresectable disease. NAC protocol completion was defined as receiving at least 3 cycles of NAC followed by either surgery, chemotherapy and/or radiation, or best supportive care. The purpose of this study was to determine the completion rate of NAC and assess the adverse events associated with treatment. Data were collected through retrospective chart review. ResultsFrom February 2016 to November 2018, 53 evaluable patients were identified. 86.8% (46/53) of patients presented in Stage IIB or higher. The completion rate of the NAC protocol was 75.5% (40/53). 94.3% (50/53) received platinum-taxane combination. 7.6% (4/52) grade 3 adverse events occurred related to chemotherapy, all hematologic. 18.8% (10/53) patients underwent surgery with 2 aborted cases due to metastatic or inoperable disease. No adverse events related to surgery were reported. 5 patients underwent adjuvant therapy after surgery due to high risk factors or incomplete pathology findings. 26 patients received adjuvant radiation (3 brachytherapy, 23 EBRT after it became available). Reported side effects related to radiation included vaginal fibrosis and skin reactions. ConclusionIn this limited-resource setting, majority of patients completed a NAC treatment strategy for cervical cancer with acceptable toxicities.

Medially Based “Abdominal Rotation Advancement Flap”: A Promising Technique for Mastectomy Defect Reconstruction in “High-Risk Patients” Awaiting Adjuvant Radiotherapy

Abstract Background Extensive postmastectomy defects and soft-tissue defects often require some additional flap cover of reconstruction after excision. The reconstruction aim in this group should be a diligent and easy closure with a quality skin cover, early recovery, and brief stay in hospital so that the patients can receive early postoperative radiotherapy/chemotherapy. Medially based abdominal transposition flap is a type C fasciocutaneous flap based on medial perforating vessels. We present our experience in significant postmastectomy defects, especially in high-risk morbid patients. Materials and Methods This is a retrospective study conducted by the department of plastic surgery, from an analysis of the breast cancer database maintained by our hospital from 2019 to 2023. A total of 826 breast cancer patients underwent surgery, of which 547 were locally advanced breast cancer (LABC) patients and 138 (32.5%) LABC patients needed flap cover for mastectomy defect. Medially based abdominal transposition flap was used in 56 of 138 (40.5%) LABC patients for defect closure, and 42 of the 56 patients were stage IIIB patients. Upfront surgery was primarily done in 20 patients and 36 patients underwent surgery after neoadjuvant chemotherapy. This analysis aimed to assess the operative duration, postoperative morbidity, hospital stay, and time taken to start adjuvant treatment by analyzing the medical records of patients who underwent this procedure. Results Fifty-six patients with breast cancer underwent surgical intervention, whereby 8 patients presented with tip and edge necrosis, and 3 patients were infected. The mean duration of operation was 58.852 minutes, and the average length of hospital stay was 5.39 days. It took 24.57 days for the patients to stabilize sufficiently for adjuvant therapy. The average age of the patients in the study was 48.73 years. Conclusion Our clinical experience has demonstrated that the medial abdominal transposition fasciocutaneous (MATF) flap represents a straightforward, reliable, and cost-effective method for managing extensive postmastectomy soft-tissue defects in a subset of patients with LABC. This group typically consists of high-risk and comorbid patients. The procedure holds considerable promise for developing countries with limited infrastructure and expertise, owing to its ease of execution and short learning curve. By its simplicity and affordability, the MATF flap offers a viable and sustainable solution for treating LABC-associated soft-tissue defects.

Comparison of Short-term Efficacy of Neoadjuvant Immunotherapy Combined with Chemotherapy and Surgery Alone for Locally Advanced Resectable Non-small Cell Lung Cancer

Lung cancer is the cancer with the highest incidence and mortality rates in China, and non-small cell lung cancer (NSCLC) accounts for 80%-85% of all malignant lung tumors. Currently, surgical treatment remains the primary treatment modality for lung cancer. In recent years, the effectiveness of immune checkpoint inhibitors for NSCLC has become a consensus, and neoadjuvant immunochemotherapy (nICT) has shown promising efficacy and safety in early to intermediate stage NSCLC. However, there are fewer studies related to nICT for locally advanced NSCLC. This study aims to evaluate the efficacy and safety of nICT therapy in locally advanced resectable NSCLC. 85 confirmed resectable stage IIIA and IIIB patients treated in the Department of Thoracic Surgery, Second Hospital of Lanzhou University, from January 2021 to April 2024, were divided into the nICT group (n=32) and the surgery alone group (n=53). Clinical baseline data, perioperative indicators, postoperative complications, imaging response rate, pathological response rate, incidence of adverse events, and quality of life were compared between the two groups. There were no statistically significant differences in clinical baseline data between the two groups (P>0.05). Incidence of choosing thoracotomy was higher in the nICT group than in the surgery alone group (P=0.002). There were no significant differences in surgical time, intraoperative blood loss, number of dissected lymph nodes, duration of chest tube placement, postoperative hospital stay, and R0 resection rate between the two groups (P>0.05). The overall incidence of postoperative complications was 31.25% in the nICT group and 22.64% in the surgery alone group, with no statistically significant difference (P=0.380). In the nICT group, the objective response rate (ORR) was 84.38%, with 5 cases of complete response (CR)(15.63%), 22 cases of partial response (PR)(68.75%), 15 cases of pathological response rate (pCR)(46.88%), and 11 cases of major pathological reaponse (MPR) (34.38%). During nICT treatment, 12 cases (37.50%) experienced grade 3 treatment-related adverse events, no death induced by adverse events or immune related adverse events. Moreover, the symptoms of the patients were improved after nICT treatment. Neoadjuvant immunochemotherapy shows promising efficacy in locally advanced resectable NSCLC, with manageable treatment-related adverse events. It is a safe and feasible neoadjuvant treatment modality for locally advanced resectable NSCLC.

A real-life study of daratumumab combinations in newly diagnosed patients with light chain (AL) amyloidosis.

Daratumumab-based regimens are the new standard of care for newly diagnosed patients with AL amyloidosis based on the results of the ANDROMEDA study. However, real-world data on daratumumab efficacy in upfront therapy in unselected patients are scanty. In the framework of a prospective observational study, we investigated the efficacy and safety of daratumumab in 88 newly diagnosed patients, including subjects with IIIb cardiac stage (26%) or myeloma defining events (29%). Daratumumab was administered with bortezomib in 50 (56%) patients, lenalidomide in 31 (35%), and monotherapy in 7 (8%). The rate of serious adverse events was low (16%). The overall hematologic response rate was 75% with 52 (59%) patients attaining at least a very good partial response (VGPR) at six months. Amongst patients evaluable for organ response, the rate of cardiac and renal responses at 6months was 31% and 21%, respectively. Comparing stage IIIb patients with the remaining ones, the rate of profound hematologic response was not significantly different (≥VGPR 57% vs. 59%, p 0.955) likewise the rate of cardiac (33% vs. 30%, p 0.340) and renal (40% vs. 16%, p 0.908) responses. Daratumumab-based regimens demonstrated to be safe and effective in treatment-naïve AL amyloidosis even in advanced stage disease.

Real-World Treatment Patterns and Survival Outcomes for Patients with Non-Metastatic Non-Small-Cell Lung Cancer in Sweden: A Nationwide Registry Analysis from the I-O Optimise Initiative.

Non-small-cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide, with ~40-50% of patients diagnosed with non-metastatic disease (stages IA-IIIC). The treatment landscape is evolving rapidly as immunotherapies and targeted therapy are introduced in the non-metastatic setting, creating a need to assess patient outcomes prior to their introduction. This real-world study using Swedish National Lung Cancer Registry data examined outcomes (overall survival (OS) and time to next treatment or death (TTNTD)) and treatment patterns for adults diagnosed with non-metastatic NSCLC. Baseline characteristics and OS from diagnosis were described for all patients; OS, treatment patterns, and TTNTD from treatment start were described for the treatment subgroup (patients diagnosed from 2014 onwards), stratified by disease stage and initial treatment. OS and TTNTD were described using the Kaplan-Meier estimator. The overall population (2008-2019) included 17,433 patients; the treatment subgroup included 5147 patients. Median OS (interquartile range) overall ranged from 83.3 (31.6-165.3) months (stage I patients) to 10.4 (4.3-24.2) months (stage IIIB patients). Among the treatment subgroup, median OS and TTNTD were longest among patients receiving surgery versus other anticancer treatments. These findings provide a baseline upon which to evaluate the epidemiology of non-metastatic NSCLC as newer treatments are introduced.

Prognostic mortality factors in advanced light chain cardiac amyloidosis: A prospective cohort study.

Predicting mortality in severe AL cardiac amyloidosis is challenging due to elevated biomarker levels and limited thresholds for stratifying severe cardiac damage. This prospective, observational, cohort study included de novo, confirmed cardiac AL amyloidosis patients at the Henri Mondor National Reference Centre. The goal was to identify predictors of mortality to enhance prognostic stratification and improve informed decision-making regarding therapy. Over the 12-year study period, among the 233 patients included, 133 were NYHA III-IV and 179 Mayo 2004 III. The independent predictors for mortality identified were hsTnT, NT-proBNP, cardiac output, and conjugated bilirubin. A novel prognostic, conditional stratification, Mondor amyloidosis cardiac staging (MACS) was developed with biomarker cut-off values for Stage 1: hsTnT≤107ng/L and NT-proBNP≤3867ng/L (n=77; 33%); for stage 2 NT-proBNP>3867ng/L (n=72; 30%). For stage 3, if troponin >107ng/L, regardless of NT-proBNP then CB 4μmol/L, was added (n=41; 17.5%) and stage 4: CB>4μmol/L (n=43; 18.5%). The median overall survival was 8months 95% CI [2-24]. At 1year, 102 (44%) patients died and the Kaplan-Meier median survival with MACS Stage 1 was not reached, while stage 2 was 15.2months (95% CI [11-18]) and stage 3, 6.6months (95% CI [1-13]). Notably, among European stage II patients, 17.1%, n=8 were MACS stage 3 and European stage IIIb 21.4% (n=23) were MACS stage 4. Importantly, among European stage IIIb patients 42.2% (n=29) were classified MACS stage 4 and 12.5% n=9 were only MACS stage 2. The Mondor prognostic staging system, including conjugate bilirubin may significantly improve prognostic stratification for patients with severe cardiac amyloidosis.

Prognostic and predictive role of liquid biopsy in lung cancer patients.

Lung cancer (LC) is a leading cause of cancer-related mortality worldwide. Approximately 80% of LC cases are of the non-small cell lung cancer (NSCLC) type, and approximately two-thirds of these cases are diagnosed in advanced stages. Only systemic treatment methods can be applied to patients in the advanced stages when there is no chance of surgical treatment. Identification of mutations that cause LC is of vital importance in determining appropriate treatment methods. New noninvasive methods are needed to repeat and monitor these molecular analyses. In this regard, liquid biopsy (LB) is the most promising method. This study aimed to determine the effectiveness of LB in detecting EGFR executive gene mutations that cause LC. One hundred forty-six patients in stages IIIB and IV diagnosed with non-squamous cell non-small cell LC were included. Liquid biopsy was performed as a routine procedure in cases where no mutation was detected in solid tissue or in cases with progression after targeted therapy. Liquid biopsy samples were also obtained for the second time from 10 patients who showed progression under the applied treatment. Mutation analyses were performed using the Cobas® EGFR Test, a real-time PCR test designed to detect mutations in exons 18, 20, and 21 and changes in exon 19 of the EGFR gene. Mutation positivity in paraffin blocks was 21.9%, whereas it was 32.2% in LB. Solids and LB were compatible in 16 patients. Additionally, while no mutation was found in solid tissue in the evaluation of 27 cases, it was detected in LB. It has been observed that new mutations can be detected not only at the time of diagnosis, but also in LB samples taken during the follow-up period, leading to the determination of targeted therapy. The results showed that "liquid biopsy" is a successful and alternative non-invasive method for detecting cancer-causing executive mutations, given the limitations of conventional biopsies.

Comparative Analysis of VMAT and IMRT Techniques: Evaluation of Dose Constraints and Bone Marrow Sparing in Cervical Cancer Patients Undergoing Chemoradiotherapy.

Carcinoma of the cervix is a globally significant cause of morbidity and mortality among women. Concurrent chemoradiotherapy, a standard approach for locally advanced cervical cancer, invariably involves pelvic irradiation. Although this strategy is effective, it inevitably affects the pelvic bone marrow, a crucial hematopoietic site, and leads to hematological toxicity The potential of IMRT to spare bone marrow in pelvic irradiation settings has been an area of significant interest, with the aim to mitigate the hematological toxicity associated with pelvic radiotherapy. Radiotherapy techniques have evolved in terms of conformity and normal tissue sparing. Our study intends to explore the use of BM sparing techniques among patients of carcinoma cervix. Twenty patients of carcinoma cervix FIGO Stage IIIB treated with concurrent chemoradiotherapy were selected for this study. The external contour of bones was delineated on planning CT as a surrogate for BM. We generated three plans on a single patient:1. without BM as the dose constraint, namely N-IMRT plan; 2. with BM constraint, namely BMS-IMRT plan; 3. VMAT plan in which BM constraint was given. The dose volume histogram (DVH) for planning target volume (PTV) and organs at risk (OAR) were analyzed. BM parameters: V10, V20, V30, V40, mean, maximum and minimum dose were compared. Results: PTV coverage was comparable in all techniques. VMAT plans resulted in superior BM sparing compared with N-IMRT plan (P-<0.001) and BMS-IMRT plan (P-<0.001, 0.021 and 0.001 respectively for V20, V30 and V40). VMAT plans had better CI compared with BMS-IMRT (P-0.002) and N-IMRT (P-0.001) plans. Our study adds to the growing evidence that VMAT might be the preferred technique for patients with carcinoma of the cervix undergoing concurrent chemoradiotherapy, as it provides comparable target coverage and better sparing of bone marrow compared to IMRT.

Daratumumab-Based Regimens Versus Cybord in Newly Diagnosed Patients with AL Amyloidosis and IIIb Cardiac Stage: A Matched Case-Control Study

Background: Improving the outcomes of light chain (AL) amyloidosis patients and advanced heart involvement, IIIb Mayo cardiac stage, is an unmet need. The standard front-line treatment has been cyclophosphamide-bortezomib-dexamethasone (CyBorD) until the approval of daratumumab with CyBorD (Dara-CyBorD) in 2021, which significantly improved the rate of hematologic response (HR) as reported by the ANDROMEDA trial. However, stage IIIb patients were excluded from the study and the best upfront treatment strategy in these patients remains to be clarified. For this reason, daratumumab was not licensed for use in stage IIIb patients in many countries. Preliminary data of the ongoing EMN22 phase II multicenter study (NCT04131309), that specifically addresses this issue using daratumumab monotherapy, are promising. Chakraboty et al. reported that Dara-CyBorD is effective in inducing profound hematologic response, at least a very good partial response (VGPR), in treatment-naïve patients with IIIb AL amyloidosis. Similar results were reported by Theodorakakou et al. using different daratumumab combinations. Finally, in a study conducted by Oubari et al. daratumumab-based regimens were associated with better clinical outcomes compared to others treatments. However, all available data on daratumumab in stage IIIb patients derive from uncontrolled studies or lacked a matched or stratified control group. We designed the present retrospective case-control study to assess the efficacy of daratumumab-based therapies versus CyBorD regimens as upfront treatment for newly diagnosed AL amyloidosis with IIIb cardiac stage. Methods:the whole study population comprises 62 matched newly diagnosed patients with IIIb stage AL amyloidosis evaluated in our center between 2012 and 2022. The daratumumab cohort is composed of all the 31 consecutive subjects treated with daratumumab-based regimens between 2021 and 2022. Thirteen patients (41%) received daratumumab in combination with bortezomib [11 (35%) associated with melphalan and dexamethasone; 2 (6%) Dara-CyBorD], 11 (35%) with lenalidomide and 7 (22%) were treated with daratumumab monotherapy. They were matched with 31 controls selected from a total of 71 subjects treated with CyBorD. Patients and controls were matched for age, estimated glomerular filtration rate, N-terminal pro-brain natriuretic peptide, free light chain and bone marrow plasma cell. Hematologic response was assessed according to the International Society of Amyloidosis criteria. The analysis of response was by intent-to-treat: patients who died before response evalutation were considered non responders . PFS is defined as the time from diagnosis to any one of the following events, whichever comes first: death, starting a second line of therapy, organ or hematologic progression as per consensus guidelines. Results:Patients' characteristics are listed in Table 1. Median follow-up of living patients was 20.5 months (95% CI: 14.3 - 55.9 months). Median OS was 4.6 months (95% CI: 3 - 6.3 months), and patients of the daratumumab cohort had a significantly prolonged OS (6.7 vs 4 months; p=0.032, Fig. 1). No differences in early mortality rate, within 3 months from diagnosis, were observed between the two cohorts (32% vs 35%, p=0.796). At three months, the overall HR rate to daratumumab was 50% [complete response (CR) 12%, VGPR 29%, partial response (PR) 9%] as compared with 21% (CR 6%, VGPR 9%, PR 6%) of the control group, p=0.021. A higher proportion of ≥VGPR was observed in the daratumumab cohort (41% vs 16%; p=0.029). Cardiac response rate was significantly more frequent in patients treated with daratumumab [8 (25%), 3 cardiac VGPR and 5 cardiac PR] compared to controls [1 (3%) cardiac PR], p=0.014. A significantly prolonged PFS was observed in patients receiving daratumumab compared to CyBorD (5 vs 2.4 months; p=0.017). Conclusions: This matched case-control study shows that even in stage IIIb patients the addition of daratumumab to CyBorD results in higher rates of deep hematologic response. This is associated with higher cardiac response rates and prolonged OS and PFS. Although the outcome of stage IIIb patients remains dismal, Dara-CyBorD was able to improve response rate and survival in these severely compromised subjects. Taken together these observations encourage the use of daratumumab combinations also in stage IIIb patients with AL amyloidosis.

Efficacy and Safety of Modified BV-AVD-R Regimen in Chinese Children with Previously Untreated Intermediate- and High-Risk Classical Hodgkin's Lymphoma: An Open Label, Non-Randomized, Single-Arm, Phase 2 Study from Single Center

Introduction Classical Hodgkin lymphoma (cHL) accounts for about 4.8% of childhood malignant neoplasm, and the incidence of cHL in Chinese children and adolescents (0-19 years old) is about 1.78/million, which is a group of relatively low malignancy and curable tumor. With the prolonged survival of children and adolescents with cHL, the incidence of muscle and skeletal malformations, lung and cardiovascular diseases, infertility and secondary tumors increased significantly during long-term follow-up. Therefore, the goal of childhood cHL treatment is to achieve and maintain the high efficacy while reduce the treatment-related complications. Brentuximab vedotin (BV), an antibody-drug conjugates (ADC) targeting CD30, has been evaluated well in American children and some regions, but no clinical studies to explore the efficacy and safety of BV in Chinese children with cHL. Therefore, the objective of our study is to evaluate the efficacy (objective response rate, including CR and PR) and safety (short - and long-term safety) of modified BV-AVD-R regimen (Brentuximab vedotin + Rituximab + Doxorubicin + Vinblastine + Dacarbazine) in Chinese children with previously untreated intermediate- and high-risk classical HL. Methods This study is a prospective study with period from October 2022 to December 2024, and planned to enroll 44 children with newly diagnosed intermediate- and high-risk classical HL. All patients will undergo PET/CT at the time of initial diagnosis and after 2 cycles of modified BV+R+AVD regimen to determine early response. Rapid early responders (RER) defined as CR after 2 cycles of therapy. Slow early responders (SER) defined as no CR (partial response (PR) or stable disease) after 2 cycles of therapy. Intermediate-risk patients were stage IA bulk/E, IB, IIA bulk/E, IIB, and IIIA. High-risk patients were stage IIB bulk/E, IIIA bulk/E, IIIB, and IVA/B(Figure 1). The primary endpoints include ORR (CR+PR) and adverse events. The secondary endpoints include progression-free survival (PFS), event-free survival (EFS) and overall survival (OS) at 6 months and 1 year. Results From October 2022 to July 2023, a total of 14 children with newly diagnosed classical HL were enrolled, and 12 patients who had completed at least 2 cycles treatment were eligible for evaluation. 9 boys and 3 girls were enrolled, with median age of 10 years (range 7-15 years). Risk group: 9 patients in high-risk group, 3 patients in intermediate-risk group; Clinical stage: 5 patients in stage IIIA, 2 patients in stage IIIB, 4 patients in stage IVA, and 1 patient in stage IVB. Pathologic subtype: 7 patients of nodular sclerosis type and 5 patients of mixed cell type. Treatment: A total of 33 cycles of modified BV+R+AVD regimen were completed, with 66 doses of BV. The median number of treatment cycles was 3 cycles (range 2-6). 11 patients achieved CR and 1 patient achieved PR after 2 cycles, and the ORR was 100% (12/12). As of July 28, 2023, 4 children had stopped follow-up and achieved CR without sequential radiotherapy. The median follow-up was 6 months (range 2-10). 12 patients successfully received and completed BV infusions, mild nausea and vomiting (10/12), alopecia (9/12) and sensory abnormalities (3/12) were observed. Serious adverse events were mainly grade ≥3 blood cell abnormalities (10/12), none of which had an impact on the treatment flow. No patient withdrew from the study, indicating good adherence to the regimen. Conclusion The risk-adapted modified BV+R+AVD regimen for newly diagnosed Chinese children and adolescents with classical HL showed favorable treatment outcomes with good early response rate and sustained response rate. The regimen could also reduce sequential radiotherapy and demonstrated well safety and tolerability. The study is still ongoing.

Orthotopic Heart Transplantation Followed By Autologous Stem Cell Transplantation in Patients with Cardiac AL Amyloidosis: Results from a Single Centre Prospective Study

Background: Patients with advanced cardiac AL amyloidosis have a dismal prognosis, with an overall survival (OS) of only 5 months for Stage IIIb patients (Palladini et al, 2023). Induction chemotherapy followed by high dose chemotherapy and autologous stem cell transplantation (HDT and ASCT) has been widely used as treatment for AL amyloidosis. However, patients with advanced cardiac AL amyloidosis are often not suitable for HDT and ASCT due to high transplant related mortality (TRM). Orthotopic cardiac transplantation (OHT) following induction treatment may improve patient fitness and thus allow HDT and ASCT to deepen and prolong responses. We present our single centre, prospective study of patients with Stage IIIa and Stage IIIb cardiac AL amyloidosis who received OHT followed by sequential HDT and ASCT. Aims: The primary outcomes were 3 year OS and progression-free survival (PFS). Efficacy and safety were assessed as secondary outcomes. Efficacy was evaluated by light chain and cardiac response after ASCT. Safety was assessed by rate of TRM, cardiac rejection, opportunistic infections, and cytopenia related complications. Methods: During 2015 to 2021, patients with Stage IIIa or Stage IIIb AL amyloidosis aged under 65 years underwent OHT followed by HDT and ASCT. Patients with multiple myeloma were excluded. At approximately 6 months following OHT, patients underwent stem cell mobilization with granulocyte colony-stimulating factor alone followed by peripheral blood apheresis stem cell collection. Mycophenolate immunosuppression was temporarily withheld during stem cell mobilization and collection. Patients then received a high dose melphalan ASCT followed by 3-6 monthly assessments. Results: Nine patients (median age of 53 years, range 47-60 years) completed both OHT and ASCT. Seven other patients were screened but did not proceed with OHT. The cohort included both stage IIIa (55%) and stage IIIb (44%) patients. Most patients received cyclophosphamide-bortezomib-dexamethasone induction therapy (89%) and one patient received lenalidomide-bortezomib-dexamethasone. The median time from diagnosis of AL amyloidosis to OHT was 11 months (range 5-57 months) and median time from OHT to ASCT was 7 months (range 5-8 months). 3 year OS was 83% and PFS was 56% (Figure 1). At a median follow up of 37 months (range 17-69 months), 89% of patients remain alive. One patient with Stage IIIa disease who underwent HDT and ASCT with progressive disease (PD) died 28 months following ASCT due to PD. Subgroup analysis demonstrated 3 year OS in Stage IIIa patients of 75% compared to 100% in Stage IIIb (p=0.48). 3 year PFS was 53% in Stage IIIa patients and 66% in Stage IIIb (p=0.8). Patients in complete remission (CR) prior to ASCT had an improved 3 year OS of 100% compared to 66% for those in partial remission (PR) or with PD (p=0.32). 3 year PFS was significantly improved at 100% when ASCT occurred in CR compared to 0% in those in PR or with PD (p=0.01) (Figure 2). All patients either maintained a CR or achieved an improved haematological response following HDT and ASCT, with 89% of patients in CR at 6 months post ASCT. At the median follow up of 37 months, 78% were in CR and 22% had PD. At last follow up, there has been no documented amyloid recurrence in a cardiac allograft. There was no TRM noted in this study. All patients had cardiac rejection with 66% developing Grade 3A/2R rejection requiring methylprednisone. The most common infective complication was CMV reactivation (44%). Other infective complications included cryptococcal infection (11%), aspergillus and MAC infection (11%) and HSV reactivation requiring hospitalization (11%). During admission for HDT and ASCT, 89% had febrile neutropenia and there were no bleeding complications. Conclusions: We have demonstrated, in a prospective design, that sequential OHT/ASCT following induction therapy is safe in patients with Stage IIIa/b cardiac AL amyloidosis without an increase in TRM. This approach was associated with excellent survival outcomes compared with historical cohorts. Given the deep and prolonged responses seen with daratumumab based induction, a risk adapted strategy may be more appropriate moving forward, with only those not achieving a haematological CR undergoing consolidation ASCT following OHT.

Survival outcomes of 2018 FIGO stage IIIC versus stages IIIAand IIIB in cervical cancer: A systematic review with meta-analysis.

To assess the difference in survival outcomes between stage IIIC and stages IIIA and IIIB in the 2018 FIGO cervical cancer staging system. The PubMed, EMBASE, MEDLINE and Web of Science were searched for articles published from November 1, 2018 to January 31, 2023. Articles published in English were considered. The included studies compared the survival outcomes of patients with cervical cancer in FIGO 2018 stage IIIC with those in stages IIIA and IIIB. Studies focused on rare histopathological types were excluded. The statistical analyses were performed using Stata 17 software. The endpoints were overall survival (OS) and progression-free survival (PFS). Ten retrospective cohort studies were eligible, involving 2113 (6.2%), 9812 (28.6%), 44 (0.1%), 10 171 (29.7%), 11 677 (34.1%) and 445 (1.3%) patients in stage IIIA, IIIB, IIIA&B, IIIC, IIIC1, and IIIC2, respectively. In the OS group, stage IIIC/C1 was significantly associated with superior survival compared with stage IIIA (hazard risk [HR] 0.62, 95% confidence interval [CI] 0.41-0.93, P = 0.022; I2 = 92.9%) and stage IIIB(A&B) (HR 0.56, 95% CI 0.44-0.71, P < 0.001; I2 = 94.0%). The FIGO 2018 stage IIIC2 was not associated with an increased mortality risk compared with stage IIIA and stage IIIB(A&B). In the PFS group, the outcome of FIGO 2018 stage IIIC/C1 was similar to stage IIIA (HR 0.66, 95% CI 0.27-1.64, P = 0.371; I2 = 65.6%), but better than stage IIIB(A&B) (HR 0.75, 95% CI 0.68-0.83, P < 0.001; I2 = 0.0%). The FIGO 2018 stage IIIC2 has similar PFS outcomes to stage IIIA and stage IIIB(A&B). Our findings demonstrate that survival outcomes of stage IIIC are no worse than those of stage IIIA and stage IIIB in the 2018 FIGO cervical cancer staging system. In cervical cancer, FIGO 2018 stage IIIC1 has significantly better OS outcomes than stage IIIA and stage IIIB.

Improved Staging of Ciliary Body and Choroidal Melanomas Based on Estimation of Tumor Volume and Competing Risk Analyses

The current, 8th edition of the American Joint Committee on Cancer (AJCC) anatomic classification and staging model for uveal melanoma does not fully separate survival estimates for patients with advanced stages of the disease (e.g., IIIB and IIIC). Furthermore, some tumors in higher size categories have a smaller volume than tumors in lower categories. Therefore, we developed a novel model for prognostication of metastatic mortality based on estimations of tumor volume. Retrospective, multicenter case series of patients with uveal melanoma involving the choroid, ciliary body, or both. Six thousand five hundred twenty-eight consecutively registered patients treated at 3 tertiary ocular oncology centers on 2 continents between 1981 and2022. Data on survival, tumor size, and extent were collected for all 6528 patients. Tumor volume was estimated using a simple equation based on largest basal diameter and thickness. Volume-based size categories and stages were developed and validated in independent patient cohorts using competing risk analyses, and correlations with cytogenetic and cytomorphologic features were examined. Cumulative incidence of metastatic death. The 6528 patients were distributed over 7 stages based on estimated tumor volume and anatomic extent (V stages IA, IB, IIA, IIB, IIIA, IIIB, and IIIC), with a 15-year incidence of metastatic death ranging from 7% to 77%. A new category, V1min, and corresponding stage IA, were introduced, indicating an excellent prognosis. Metastatic mortality in V stage IIIC was significantly higher than that in V stage IIIB (P= 0.03), whereas incidence curves crossed for patients in AJCC stages IIIC vs. IIIB (P= 0.53). Univariable and multivariable competing risk regressions demonstrated higher Wald statistics for V stages compared with AJCC stages (1152 vs. 1038 and 71 vs. 17, respectively). The frequency of monosomy 3, gain of chromosome 8q, and epithelioid cytomorphologic features increased with tumor volume (R2= 0.70, R2= 0.50, and R2= 0.71, respectively; P < 0.001) and showed similar correlations with both AJCC and V stages. Anatomic classification and staging of ciliary body and choroidal melanomas based on estimation of tumor volume improves prognostication of metastatic mortality. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Real-world treatment patterns and survival outcomes for patients with stage III non-small cell lung cancer in Spain: a nationwide cohort study.

The burden of non-small cell lung cancer (NSCLC) remains high in Spain, with lung cancer accounting for 20% of cancer-related deaths annually. Programs such as the Spanish Thoracic Tumour Registry (TTR) and the global I-O Optimise initiative have been developed to observe patients in clinical practice with the aim of improving outcomes. This analysis examined treatment patterns and survival in patients with stage III NSCLC from the TTR. These patients represent a heterogenous group with complex treatment pathways. The TTR is an ongoing, observational, prospective, and retrospective cohort multicentre study (NCT02941458) that follows patients with thoracic cancer in Spain. Adults aged ≥18 years with stage IIIA/IIIB NSCLC enrolled in the TTR between 01 Jan 2010 and 31 Oct 2019 were included in this analysis. Initial treatment received was described by cancer stage and histology (squamous and non-squamous NSCLC). Kaplan-Meier estimates of progression-free survival (PFS) and overall survival (OS) were calculated over a 5-year period. A total of 1,838 patients were included in the cohort, including 1,082 with stage IIIA (58.9%) and 756 with stage IIIB (41.1%). Median follow-up was 18.3 months. The median age of patients was 66 years, and most had non-squamous NSCLC (54.0%), were male (81.2%), and were active or former smokers (93.4%). Overall, 26.3% of patients received surgical resection (37.0% for stage IIIA and 11.1% for stage IIIB). The most frequent initial treatment received was concurrent chemoradiotherapy for stage IIIA (30.2%) and stage IIIB (37.0%) patients. Median OS was lower in patients with stage IIIB than stage IIIA (28 vs. 37 months) disease and was lower for patients with squamous than non-squamous histology (19 vs. 26 months). Median PFS and OS varied when patients were stratified by initial treatment. This TTR analysis describes the clinical reality surrounding the initial management and survival outcomes for stage III NSCLC in Spain and presents survival outcomes comparable with other real-world evidence. It provides insights into the diverse approaches used before the availability of immunotherapies and targeted treatments in the non-metastatic NSCLC setting.

Cervical Cancer Progression in Patients Waiting for Radiotherapy Treatment at a Referral Center in Ethiopia: A Longitudinal Study

ABSTRACT Nonmetastatic cervical cancer is a highly curable malignancy, and radiotherapy (RT) remains the mainstay treatment. Early initiation is critical, and the optimal time to initiate RT for cure is 6 weeks, with a reported 15% decrease in 3-year overall survival for those who wait 40 days. There is considerable variation in the waiting time to initiate RT between countries, with a median time of 27.2 days in Ontario, Canada and 108 days in South Africa. Real-world evidence of cancer progression because of treatment delay is scarce in low-income countries. Ethiopia, a country of 120 million, had a single machine at Tikur Anbessa Specialized Hospital (TASH) until it acquired a linear accelerator very recently. This study aimed to assess the extent of delay in receiving RT and the effect of delay on the natural disease court in patients with cervical cancer treated at TASH. This study was conducted at TASH between January 2019 and May 2020 and evaluated patients at different time points before and after RT. All individuals who were diagnosed with cervical cancer (stage IIB to stage IVA) and booked for RT at TASH were included. Concurrent chemoradiotherapy was administered for cervical cancer with weekly cisplatin as a chemotherapy agent. A total of 115 patients were included in this study. The median time between pathologic diagnosis and booking RT was 19 days, and the median time from booking to RT initiation was 458 days. The total median time from diagnosis to treatment was 477 days, and the median time to disease progression was 51 days. During the waiting period for RT, the stage was reassessed for 105 patients. The number of patients in stage IIB, IIA, and IIIB decreased during this period, whereas the number of patients in stage IVA increased from 20 (17.4%) to 30 (26.1%), 2 (1.8%) developed distant metastasis to the lungs (stage IVB), and 37 died before receiving a phone call for RT. Of 115 patients booked to receive CCRT, only 9 (7.8%) received CCRT, 80 (69.9%) received a single shot of palliative RT due to disease progression, and 25 (21.7%) did not receive RT at all. The mean and median survival times were 20.1 months (95% confidence interval [CI], 18.3–22.7) and 21 months (95% CI, 18.3–23.8), respectively. Waiting time, stage at presentation, distant metastasis during the waiting time, hydronephrosis during the waiting time, and type of treatment were significantly associated with survival. Multivariate cox regression using these variables found that patients with stage IIIB were 2.2 times more likely to die than those with stage IIB (adjusted hazards ratio, 2.2; 95% CI, 1.07–4.48), and patients with stage IVA were 20.95 times more likely to die than patients with stage IIB (adjusted hazards ratio, 20.95; 95% CI, 6.26–70.03). Prolonged waiting time increased the mortality rate of cervical cancer by 2.9 (95% CI, 1.07–4.5). This study provides a significant advancement in our understanding of cervical cancer care in low-income countries. The median waiting time diagnosis to treatment was 477 days, whereas the median waiting period for disease progression was 51 days, resulting in unnecessary disease progression, change in treatment intent from curative to palliative, and increased mortality. These findings highlight the need to increase access to RT services in lower-income nations to reduce wait times and provide better cancer care.

Effect of sevoflurane on CD4+CD25+FOXP3+ regulatory T cells in patients with gastric cancer undergoing radical surgery.

In this study, the proportion of CD4+CD25+FOXP3+ regulatory T (Treg) cells in CD4+ T cells in the peripheral blood of gastric cancer patients before anesthesia induction (T1), after surgery (T2) and the first day after surgery (T3) was studied to explore the effect of sevoflurane and propofol anesthesia on the prognosis of gastric cancer patients. Forty patients with advanced gastric cancer were recruited and randomly divided into the sevoflurane group (S group) and the propofol group (T group). Flow cytometry was used to detect the proportion of CD4+CD25+FOXP3+ Treg cells in CD4+ T cells in the peripheral blood of patients with T1, T2 and T3, respectively. Compared with stage ⅡB, the proportion of CD4+CD25+FOXP3+ Treg cells in T1, T2 and T3 of stage ⅢA and stage ⅢB patients was increased. Compared with the T group, the expression of CD4+CD25+FOXP3+ Treg cells in the peripheral blood of T2 and T3 in the S group was decreased. The results showed that the expression of CD4+CD25+FOXP3+ Treg cells might be related to the TNM stage of gastric cancer and sevoflurane could alleviate the inhibition of postoperative immune function more than propofol. Sevoflurane effectively reduced the expression level of CD4+CD25+FOXP3+ Treg cells in peripheral blood of T2 and T3 of patients with gastric cancer, providing the theoretical basis for the selection of surgical anesthetics for patients with gastric cancer.

Enrolling patients in Cardiac Amyloid Reaching for Extended Survival (CARES) trials: Two placebo-controlled, double-blind, randomized, international phase 3 trials assessing CAEL-101 in patients with Mayo stage IIIa or stage IIIb AL amyloidosis.

TPS8071 Background: Light-chain (AL) amyloidosis is a rare, progressive, systemic disorder caused by plasma cell dyscrasia (PCD). Amyloid fibrils deposit in organs leading to progressive organ damage and death. Prognosis is poor for patients with cardiac involvement. Median survival is 24 and 4 months for patients in Mayo Stages IIIa and IIIb (based on the 2013 European Modification of the Mayo 2004 staging criteria), respectively. The standard of care (SoC) is anti-PCD therapy to suppress amyloid fibril generation. As yet, there are no therapies that remove deposited fibrils. CAEL-101 is a monoclonal antibody that binds to amyloid fibrils and may facilitate their systemic removal, improve organ function, and patient survival. These ongoing trials will evaluate the efficacy and safety of CAEL-101 as first-in-class treatment to reduce amyloid burden in patients with cardiac AL amyloidosis. Notably, 301 (Mayo Stage IIIb) is the first randomized, placebo-controlled efficacy clinical trial to formally assess the effects of a pharmacological in this severely ill population. Because the median expected survival for Mayo Stage IIIb patients is far shorter than for Mayo Stage IIIa patients, the resulting sample size required for the Mayo Stage IIIb study is less than for the Mayo Stage IIIa study. The objective of these trials is to evaluate the efficacy and safety of CAEL-101 when administered concurrently with SoC anti-PCD therapy in treatment-naïve patients with cardiac AL amyloidosis in Mayo Stages IIIb (NCT04504825; 301) or IIIa (NCT04512235; 302). Methods: These international, multicenter, double-blind, randomized, phase 3 trials, initiated in 2020, are enrolling patients at &gt; 100 sites in &gt; 20 countries. Newly diagnosed adults with AL amyloidosis stage IIIb or IIIa measurable hematologic disease, and histopathological diagnosis of amyloidosis with cardiac involvement are eligible. Patients with other forms of amyloidosis, symptomatic orthostatic hypotension, or supine systolic blood pressure &lt; 90 mm Hg are ineligible. Patients in Mayo Stages IIIb (N = 124) and IIIa (N = 267) are being randomized 2:1 to receive once-weekly IV infusions of CAEL-101 (1000 mg/m2) or placebo for 4 weeks, followed by maintenance dosing every 2 weeks. In these event-driven studies, treatment will continue to a minimum of 101 and 79 events for 301 and 302, respectively. Patients will receive concurrent institutional SoC anti-PCD therapy at the discretion of the investigator. Overall survival (primary endpoint) will be analyzed via time-to-event log-rank statistics. Secondary endpoints include functional outcomes, quality of life, and echocardiography. Clinical trial information: NCT04504825 , NCT04512235 .

Clinical profile of geriatric cervical cancer patients in a tertiary hospital in Surabaya, Indonesia

HIGHLIGHTS Squamous cell carcinoma majorly covered in histopathologic of the records, while adenosquamous followed second. Most of the subjects were referral patients to Dr. Soetomo General Academic Hospital. They were mostly originated from Java outside Surabaya. ABSTRACT Objective: To identify the distribution of age, histopathology type, clinical stage, treatment type, parity, first complaint, and referral origin of geriatric cervical cancer patients at Dr. Soetomo General Academic Hospital, Surabaya, Indonesia. Materials and Methods: This study was a retrospective study observing data from medical records and presented the data descriptively. The medical records were taken from Oncology Outpatient Clinic in Dr. Soetomo Hospital, from 2020-2021, covering geriatric patients aged more than 55 years old. The data were screened and processed. Results: At Dr. Soetomo Hospital, in 2020-2021 there were 228 cervical cancer patients. From 176 patient data that met the inclusion criteria, the average age was 65.38 ± 4.86 years, with 4 types of histopathology dominated by squamous cell carcinoma (82.39%), adenocarcinoma (11.93%), adenoquamous (3.41%) and others (4%), divided into 8 clinical stages and dominated by stages IIIB (77.27%), IIB (15.9%), IVB (2.84%), IIIA and IB had same number (1.14%), 1A (0.57%) and no cases of IIA were found. The treatments were dominated by chemotherapy (86.36%), radiation therapy (7.38%), no treatment (3.41%), hysterectomy (1.7%), while for conization and palliative therapy each in 1 case (0.57%). Most experienced 3 parity (29.5%), followed by 4 parity (17.61%), &gt;5 (13.07%), 5 (10.23%), 1 (6.82%) and no parity (2.27%). The three first complaints were. vaginal bleeding (82.38%), vaginal discharge (46.02%), and pain (82.38%), and the patients were dominated by referrals from Java Island other than Surabaya City (78.40%), outside Surabaya in Java Island as many as 36 referrals (20.45%) and outside Java Island 2 referrals (1.14%). Conclusion: There were 176 geriatric patients with cervical cancer at Dr. Soetomo General Academic Hospital, Surabaya, Indonesia, in the 2020-2021 period, dominated by age 56-65 years, the histopathology type of squamous cell carcinoma, stage IIIB patients, most received therapy was chemotherapy, most were multiparous with 3 parities, the majority experienced complaints of vaginal bleeding when diagnosed with cervical cancer, and were dominated by referrals from Java Island outside Surabaya.

Abstract LB163: A microfluidic platform for developing circulating tumor cells (CTCs) organoids for precision medicine in pancreatic cancer

Abstract Introduction Pancreatic ductal adenocarcinoma (PDAC) is predicted to be the second leading cause of cancer death in the US by 2030. Besides the late detection and lack of effective treatments, the greatest treatment hurdle to PDAC is the ineffectiveness of patient-derived tumor models. Precision medicine-based treatment decisions require the generation of consistent and trackable complex organoid models that is not achievable by tissue biopsies. Liquid biopsies such as blood, instead, contain circulating biomarkers released by the tumor, among which especially interested in for this study are circulating tumor cells (CTCs). This work develops microfluidic 3D organoids from CTCs to be used as a precision medicine tool to predict and guide the drug response of early stage I-IIB (PDAC) patients. Experimental Methods CTCs are isolated from PDAC patient blood samples using microfluidic Labyrinth following removal of red blood cells with 6% dextran. Collected cells post-isolation are immunofluorescence (IF) stained with DAPI (nuclei), CD45 (leukocyte), pancytokeratin (type I/II cytokeratin 1-8, 10, 14- 16 and 19), Vimentin, and Epithelial cell adhesion molecule (EpCAM) to identify CTCs and characterize their phenotypes. The mold of the microfluidic platform for CTC organoids is fabricated with the standard SU-8 photolithography. The PDMS-based device is tested with a low seeding number of a pancreatic cancer CTC cell line labeled fluorescently. Decellularization of cancer associated fibroblasts (CAFs) generates the in vitro matrix that supplies amino-acid precursors for PDAC metabolism, promoting CTC organoid formation. Serial images of cell growth are obtained throughout the course using a Ti-20 microscope. After each 7-day culture, organoids are dissociated from the device and IF stained using a similar panel as above (with Ki67 marker instead of CD45 for cell proliferation). Preliminary gemcitabine dosage-performance analysis is performed on-chip. Results CTC count from the tested patient panel (n=16) averages 17.0±8.4/mL of blood. CAFs are successfully decellularized on-chip and the embedded pancreatic CTC cell line growth curve is generated. IF staining of the dissociated cells from the organoids confirms the proliferation of the loaded pseudo-CTCs. Conclusion The work above demonstrates the successful isolation of CTCs from PDAC patient blood samples and an engineered microfluidic platform to expand low abundance of cells into organoids. It has a potential to be tested and employed to expand CTCs from PDAC into organoids for drug screening. Citation Format: Yu Zhang, Scott Smith, Minal Nenwani, Valerie Gunchick, Vaibhav Sahai, Sunitha Nagrath, Deepak Nagrath. A microfluidic platform for developing circulating tumor cells (CTCs) organoids for precision medicine in pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB163.

Adjuvant chemoradiotherapy in resected gallbladder cancer: A SEER-based study

BackgroundThe prognosis of gallbladder cancer (GBC) is dismal. This study aimed to compare the outcomes of adjuvant chemoradiotherapy (ACR) with those of surgery alone (S) and adjuvant chemotherapy (AC). MethodThe Surveillance, Epidemiology, and End Results (SEER) Program database was used to identify patients diagnosed with GBC and undergoing surgery between 2004 and 2015. The patients were divided into the S, AC, and ACR groups according to their treatment. Categorical variables were compared by Pearson’s chi-square test, and a 1:1:1 propensity score matching analysis (PSM) was performed. Overall survival was assessed by Kaplan-Meier curves with log-rank tests. Subgroup analyses were conducted. ResultA total of 5451 patients were identified in the SEER database. After PSM, the two-year survival among patients who received S, AC, and ACR was 36%, 39%, and 45%, respectively. ACR was associated with improved two-year survival (p < 0.001), while the survival rates were similar in the AC and S groups (p = 0.127) but better in the ACR group than in the AC group (p = 0.012). Subgroup analyses indicated that while the two-year survival rates did not differ significantly in stage II GBC patients between the groups (all p > 0.05), ACR was associated with significantly improved two-year survival in stage Ⅲa (p = 0.008), Ⅲb (p < 0.001), and Ⅳb (p < 0.001) GBC patients. ConclusionThe combination of surgery and ACR as the treatment modality provided greater survival benefits for GBC patients, particularly for those with advanced tumor staging.