Patients Underwent Induction Chemotherapy Research Articles

Assessment of measurable residual disease after induction chemotherapy in acute lymphoblastic leukemia patients in a tertiary care hospital

Background: Measurable residual disease (MRD) is a crucial prognostic factor in acute lymphoblastic leukemia (ALL), influencing treatment outcomes and long-term survival. This study investigates the prevalence of MRD post-induction chemotherapy and its association with clinical, demographic, and biochemical markers in ALL patients at a tertiary care hospital. Methods: This observational cross-sectional study was conducted at Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh, from August 2021 to July 2022. A total of 22 newly diagnosed ALL patients underwent induction chemotherapy and MRD evaluation using flow cytometry. Clinical signs, demographic data, and laboratory findings, including serum creatinine, uric acid, and BCR-ABL1 status, were recorded. Statistical analyses assessed the relationships between MRD status and various predictors. Results: Of the 22 patients, 7 (31.82%) remained MRD positive after induction chemotherapy. Anaemia was prevalent, affecting 20 participants (90.91%). MRD positive patients had higher serum creatinine (mean 1.23±0.31 mg/dl) and uric acid levels (mean 7.09±1.62 mg/dl) compared to MRD negative patients. None of the MRD positive patients tested positive for BCR-ABL1. Six of the 7 MRD positive patients were male (85.71%). Bone marrow analysis showed 5 MRD positive patients (71.43%) achieved complete remission. Risk stratification did not significantly correlate with MRD status. Conclusions: MRD is a critical prognostic tool in ALL management, correlating with higher biochemical markers of tumor burden and a distinct clinical profile. These findings support integrating MRD assessment with detailed clinical and laboratory evaluations to refine treatment strategies and improve patient outcomes in ALL.

Stereotactic Magnetic Resonance-Guided Daily Adaptive SABR (SMART) for Localised Non-Metastatic Pancreatic Cancer: First Reported Clinical Outcomes From the UK

AimsPrognosis of locally advanced pancreatic cancer (LAPC) remains poor with limited therapeutic options. Radiation therapy in pancreatic cancer has been restricted by the disease's proximity to radiosensitive organs at risk (OAR). However, stereotactic magnetic resonance-guided adaptive radiation therapy (SMART) has demonstrated promise in delivering ablative doses safely. We sought to report clinical outcomes from a UK-based Compassionate Access Programme that provided access to SMART to patients with LAPC. Materials and methodsThis was a registry retrospective study conducted at a single centre with access to SMART. Patients with LAPC were treated with prescription dose of 40 Gy in 5 fractions. The planning objective was that 98% of PTV received ≥95% of the prescribed dose, prioritising duodenal, stomach and bowel UK SABR consortium constraints. Daily online adaptation was performed using magnetic resonance guidance and on-table re-optimisation. 0–3 months and > 3-month post-treatment-related toxicities, local progression-free survival, metastatic-free survival and overall survival were evaluated. Results55 patients were treated with SMART at our institution from 2020 to 2022. Median follow-up from date of diagnosis was 17 months (range 5–37 months). Median age was 69.87% of patients underwent induction chemotherapy. 71% of patients reported 0–1 grade acute toxicity only. No grade >3 acute toxicity was reported. 5 patients (9%) reported a grade 3 toxicity (fatigue, nausea, abdominal pain, duodenal stricture). No grade >3 toxicity after 3 months was reported. 6 (10%) of patients had grade 3 toxicity (fatigue, nausea, abdominal pain, duodenal haemorrhage). Median local PFS post diagnosis was 17 months (95% CI 15.3–18.7). Median OS post diagnosis was 19 months (95% CI 15.9–22.1). One-year local control post SMART was 65%. ConclusionThis is the first UK-reported experience of MR-guided daily adaptive pancreatic SABR. SMART shows promise in delivering ablative doses with acceptable toxicity rates and good clinical outcomes.

The Outcomes of Neoadjuvant Chemoradiotherapy Using Moderately Hypofractionated Intensity Modulated Radiotherapy for Borderline Resectable Pancreatic Cancer

Complete resection of borderline resectable pancreatic cancer (BRPC) is difficult because of its invasion to the vital vessels. Although neoadjuvant therapy is recommended for BRPC, its optimal regimens remain unclear. Neoadjuvant chemoradiotherapy using moderately hypofractionated intensity-modulated radiotherapy (NAC-MH-IMRT) has potentials to improve the treatment outcomes with shorter treatment periods. Therefore, we evaluated the outcomes for BRPC patients treated with NAC-MH-IMRT. Between February 2013 and June 2021, patients with BRPC treated with NAC-MH-IMRT at our institution were evaluated. All patients were classified as BRPC-A and BRPC-V according to NCCN guidelines. Information regarding patient status, tumor and treatment characteristics, margin-negative resection (R0) rates, histological effects assessed by Evans classification, and outcomes were obtained from the clinical records. Overall survival (OS) and progression-free survival (PFS) were calculated by the Kaplan-Meier method from the start date of any first treatment for BRPC. Toxicity was evaluated by CTCAE version 5.0. Sixty-eight patients were included in this study (Table). All patients underwent induction chemotherapy, and 67 were treated with IMRT at 42 Gy in 15 fractions with concurrent gemcitabine (for 65) or S-1 (for 2). All patients achieved completion of radiotherapy. Fifty-seven of the 68 patients (83.8%) underwent surgical exploration, and 48 patients (70.6%) had a resection. The R0 resection was achieved in 44 patients, and the R0 resection rate was 91.7% in resected patients. Therapeutic effects by Evans classification showed as below: Grade 1/2a/2b/3/4 = 6 (12.5%)/17 (35.4%)/17 (35.4%)/7 (14.6%)/1 (2.1%). Adjuvant chemotherapy was performed for 41 patients, and S-1 and gemcitabine were used for 40 and 1 patient(s), respectively. The median follow-up time and median survival time (MST) were 23.6 months and 42.7 months, and 2-year OS and PFS were 67.3% and 30.2%, respectively. Recurrence was observed in 54 patients (79.4%), and the first recurrence pattern was as follows: 7 (13.0%)/42 (77.8%)/5 (9.3%) patients had local recurrence, distant metastases, and both of them, respectively. Regarding ≥ Grade 3 gastrointestinal toxicity related NAC-MH-IMRT, grade 3 ileus was observed in 1 patient. NAC-MH-IMRT for BRPC showed preferable outcomes and acceptable toxicities with high completion rate.

Acute leukemias in pregnant women: Results of a retrospective study at a local tertiary-care hospital in Japan.

Leukemia may rarely develop in a woman during pregnancy, posing clinical challenges to the patient, fetus, family, and medical staff managing malignancy and pregnancy. We retrospectively analyzed cases of pregnancy-associated leukemia consecutively diagnosed and treated at a local tertiary-care hospital in Nagano, Japan, over the past 20 years. Five cases were identified among 377,000 pregnancies in the area (one in every 75,000 pregnancies), all involving acute leukemia (three acute myelogenous leukemia [AML] and two acute lymphoblastic leukemia [ALL]). The cases were diagnosed in the first trimester (n = 1), second trimester (n = 3), or third trimester (n = 1). There were no apparent pregnancy-associated delays in diagnosing and treating the cases. Three patients underwent induction chemotherapy during pregnancy, two of whom eventually delivered healthy babies. One of the five patients chose abortion before chemotherapy initiation. Two cases showing high-risk features at the diagnosis (AML with an FLT3-ITD mutation [n = 1] and relapsed ALL [n = 1]) eventually died despite consolidative allogeneic hematopoietic stem cell transplantation. Our results suggested that patients with pregnancy-associated acute leukemia can be treated similarly to nonpregnant patients, although pregnancy imposes particular clinical challenges that should be resolved with multidisciplinary care.

Postoperative radiotherapy with modern techniques does not improve survival for operable stage IIIA-N2 non–small cell lung cancer

ObjectivesThis study aims to evaluate whether postoperative radiotherapy using newer techniques (intensity-modulated radiotherapy [IMRT]) is associated with improved survival for patients with stage IIIA-N2 non–small cell lung cancer (NSCLC) who underwent complete resection. MethodsThe overall survival of patients with stage IIIA-N2 NSCLC who received postoperative IMRT versus no postoperative IMRT following induction chemotherapy and lobectomy in the National Cancer Database from 2010-2018 was assessed via Kaplan-Meier analysis, Cox proportional hazards analysis and propensity score-matched analysis. Additional survival analyses were also conducted in patients with completely resected stage IIIA-pN2 NSCLC who had upfront lobectomy (without induction therapy) followed by adjuvant chemotherapy alone or adjuvant chemotherapy with postoperative IMRT. Only patients receiving IMRT, which is a newer, more conformal radiotherapy technique, were included. Patients with positive surgical margins were excluded. ResultsA total of 3203 patients with stage IIA-N2 NSCLC who underwent lobectomy were included. Five hundred eighty-eight (18.4%) patients underwent induction chemotherapy followed by lobectomy, and 2615 (82%) underwent lobectomy followed by chemotherapy. In unadjusted, multivariable-adjusted, and propensity score--matched analyses, there were no significant differences in overall survival between the patients who also received postoperative IMRT versus those who did not. ConclusionsIn this national analysis, the use of postoperative IMRT was not associated with improved survival in patients with completely resected stage IIIA-N2 NSCLC with or without induction chemotherapy.

Computed tomography-based radiomic to predict resectability in locally advanced pancreatic cancer treated with chemotherapy and radiotherapy.

BACKGROUNDSurgical resection after neoadjuvant treatment is the main driver for improved survival in locally advanced pancreatic cancer (LAPC). However, the diagnostic performance of computed tomography (CT) imaging to evaluate the residual tumour burden at restaging after neoadjuvant therapy is low due to the difficulty in distinguishing neoplastic tissue from fibrous scar or inflammation. In this context, radiomics has gained popularity over conventional imaging as a complementary clinical tool capable of providing additional, unprecedented information regarding the intratumor heterogeneity and the residual neoplastic tissue, potentially serving in the therapeutic decision-making process.AIMTo assess the capability of radiomic features to predict surgical resection in LAPC treated with neoadjuvant chemotherapy and radiotherapy.METHODSPatients with LAPC treated with intensive chemotherapy followed by ablative radiation therapy were retrospectively reviewed. One thousand six hundred and fifty-five radiomic features were extracted from planning CT inside the gross tumour volume. Both extracted features and clinical data contribute to create and validate the predictive model of resectability status. Patients were repeatedly divided into training and validation sets. The discriminating performance of each model, obtained applying a LASSO regression analysis, was assessed with the area under the receiver operating characteristic curve (AUC). The validated model was applied to the entire dataset to obtain the most significant features.RESULTSSeventy-one patients were included in the analysis. Median age was 65 years and 57.8% of patients were male. All patients underwent induction chemotherapy followed by ablative radiotherapy, and 19 (26.8%) ultimately received surgical resection. After the first step of variable selections, a predictive model of resectability was developed with a median AUC for training and validation sets of 0.862 (95%CI: 0.792-0.921) and 0.853 (95%CI: 0.706-0.960), respectively. The validated model was applied to the entire dataset and 4 features were selected to build the model with predictive performance as measured using AUC of 0.944 (95%CI: 0.892-0.996).CONCLUSIONThe present radiomic model could help predict resectability in LAPC after neoadjuvant chemotherapy and radiotherapy, potentially integrating clinical and morphological parameters in predicting surgical resection.

Multimodal therapy for synchronous bone oligometastatic NSCLC: The role of surgery

The study aimed to assess the feasibility of radical surgical treatment for selected bone-oligometastatic non-small cell lung cancer (NSCLC) patients and to identify prognostic factors associated with survival. The clinical records of 27 patients with bone synchronous oligometastatic NSCLC were retrospectively analyzed. Thirteen (48.1%) bone metastases were treated by surgery and 14 (51.9%) by local radiotherapy. Eighteen (66.7%) patients underwent induction chemotherapy before lung surgery, and 3 (11.1%) concurrent radiotherapy. Pulmonary surgery was a major lung resection in 23 (85.2%) cases. Intraoperative and 30-days mortality was null. Only one major (ARDS) and 10 (37.04%) mild complications (like air leakage, arrhythmia, and mucus retention) were recorded. 1-year and 5-years OS from the diagnosis and 1-year, 3- years disease-free survival (DFS) were 96%, 38%, and 66%, 30%, respectively. After stepwise Cox regression analysis, local recurrence (p = 0.05) and metachronous metastases (p = 0.04) maintained their independent prognostic value as overall survival negative determinants. Nodal upstaging (p = 0.04) and nonsurgical treatment of bone lesion (p = 0.03) turned out to be independent risk factors for shorter DFS; the vertebral localization of bone metastases showed only a remarkable trend towards significance (p = 0.06) as a risk factor for a worse DFS. In selected patients, surgical treatment of primary NSCLC and bone synchronous metastasis seems to be safe and feasible and rewarding survivals may be expected.

Quality of Life Is Not Deteriorated After Extrapleural Pneumonectomy vs. (Extended) Pleurectomy/Decortication in Patients With Malignant Pleural Mesothelioma.

Background: Extrapleural pneumonectomy (EPP) for malignant pleural mesothelioma (MPM) is highly abandoned due to high morbidity and mortality rates and impaired quality of life (QoL). However, there are still rare indications for this intervention. The aim of this longitudinal prospective study was to monitor QoL and lung function in patients undergoing EPP and compare the outcomes with extended pleurectomy/decortication [(E)PD].Methods: Between June 2013 and June 2017, 42 patients underwent induction chemotherapy followed by either EPP (n = 7) or (E)PD (n = 35). All patients filled out the EORTC QLC-C15-PAL, –LC13, and SF-36 self-rating questionnaires pre-operatively, 6 weeks and 4 months after the operation. Additionally, lung function was measured pre-operatively and 4 months post-operatively.Results: We observed no significant differences in all QoL categories (general global health, pain, and dyspnea) between both surgical procedures, over the whole observation period. Moreover, a general tendency toward restoration of the pre-operative QoL status was documented at 4 months after the both operations. Forced expiratory volume in 1 s (FEV1) showed a significant decrease after surgery in both the groups [EPP group p = 0.06 and (E)PD group p < 0.001]; also, the forced volume vital capacity (FVC) significantly decreased (EPP group p = 0.046 P/D group <0.001). Diffusion capacity did not show significant changes.Conclusion: According to these results, QoL is no longer severely impaired after EPP compared with EPD, and therefore should not be used as an argument against EPP in principle. However, indication has to be carefully evaluated for each patient.

Distal pancreatectomy with en bloc celiac axis resection (DP‐CAR) and arterial reconstruction: Techniques and outcomes

Ischemic complications are still prevalent after distal pancreatectomy with en bloc celiac axis resection (DP-CAR) despite the use of preoperative arterial embolization. We described our institutional experience with arterial reconstruction during DP-CAR. We retrospectively reviewed short- and long-term outcomes of all DP-CAR performed for pancreatic adenocarcinoma between January 1, 1995 and March 30, 2020. Outcomes were compared according to the presence of arterial reconstruction. Sixty consecutive DP-CARs were reviewed. Most patients underwent induction chemotherapy (85%) based on FOLFIRINOX protocol (80.3%). The hepatic artery was reconstructed in 50 patients (83.3%). The left gastric artery was reconstructed in 4 and preserved in 14 patients. A venous resection was associated during 44 DP-CARs (36 segmental venous resections/8 lateral venous resections). Ninety days mortality was 5.0% with 48.3% (n = 29) overall rate of morbidity. Postoperative outcomes in term of mortality, morbidity, and ischemic events between patients with and without arterial reconstruction were similar despite a higher rate of venous resection (81% vs. 40%; p = 0.005) and more complex cases (Mayo clinic DP-CARs class1B, 2A, and 3A) in the reconstructed group. Arterial reconstruction represents a safe surgical option during DP-CAR to lessen postoperative ischemic events. This technique, reserved to high volume centers expert in vascular resection during pancreatectomy, deserves further comparison with standard technique in a larger setting.

LINC-33. MULTIMODALITY MANAGEMENT OF PAEDIATRIC PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA- UPDATED EXPERIENCE FROM A REGIONAL CANCER CENTRE IN NORTH INDIA

Paediatric primary central nervous system lymphoma(PCNSL) constitutes 1% of all PCNSLs. Data pertaining to paediatric PCNSL (2016–19) was abstracted by retrospective chart review. We identified 7 paediatric patients with PCNSL. None had congenital or acquired immunodeficiency. The median age at presentation was 13 years. The male to female ratio was 4:3. The median ECOG performance status was 2. On neuro-imaging, 3 patients had solitary and 4 patients had multiple lesions. CSF cytology showed atypical cells in 1 patient. None had ocular involvement. Systemic lymphoma work-up was negative in all. Biopsy and resection of tumour were done in 4 patients each. Histopathology revealed DLBCL in 6 and B-cell NHL in 1 patient. All patients underwent induction chemotherapy (median-5 cycles)- modified DeAngelis protocol (IV Methotrexate-2.5g/m2,IT Methotrexate-12 mg,Vincristine,Procarbazine and Rituximab-375mg/m2 every 2 weeks) in 6 and single agent Methotrexate -3.5g/m2 every 3 weeks in 1 patient. Severe haematological toxicities included grade 3 neutropenia, leucopenia and febrile neutropenia in 2,1 and 1 patient respectively. Radiotherapy(RT) was administered in all-whole brain RT(36-45Gy/20-25fractions/4-5weeks) in 6 patients and craniospinal RT(36Gy/18fractions/3.5weeks) followed by whole brain RT(9Gy/5fractions/1week) in 1 patient(with positive CSF cytology). Subsequently consolidation chemotherapy with 2 cycles of Cytarabine(3g/m2 IV D1-2 every 3 weeks) was administered in 5 patients. After a median follow-up of 14 months(mean-18.2 months), all patients are in complete radiological remission. Paediatric PCNSL is a rare tumour entity and multimodality management with high dose Methotrexate and Rituximab based chemo-immunotherapy and cranial radiotherapy leads to excellent early clinical outcome.

The Impact on Outcome by Adding Bevacizumab to Standard Induction Chemotherapy Prior to Mesothelioma Surgery: A Retrospective Single Center Analysis.

ObjectivesAdding bevacizumab, an anti-Vascular Endothelial Growth Factor (VEGF), to platinum-based chemotherapy/pemetrexed in 1st line treatment of advanced malignant pleural mesothelioma (MPM), significantly improved overall survival. However, increased high grade bleeding after operation was reported in patients with colorectal cancer who previously received bevacizumab. In the present analysis, we assessed for the first time the impact of adding bevacizumab to induction chemotherapy prior to surgery for mesothelioma patients.MethodsTwo hundred twenty-seven MPM patients, intended to be treated with induction chemotherapy followed by surgery at the University Hospital of Zurich between 2002 and December 2018, were included in the present analysis. After propensity score matching for gender, histology and age (1:3 ratio), data from 88 patients were analyzed. Sixty-six patients underwent induction chemotherapy (with cis-/carboplatin and pemetrexed: control group) alone and 22 patients underwent induction chemotherapy with the addition of bevacizumab (bevacizumab group) prior macroscopic complete resection (MCR). Perioperative and long-term outcome variables were analyzed.ResultsPatients undergoing combination treatment with bevacizumab had a significantly better response than with chemotherapy alone as assessed by modified RECIST (p=0.046). Intraoperative complications in the bevacizumab group (one patient), or in the control group (three patients) were not related to intraoperative bleeding. Postoperative transfusion of blood products occurred in a larger amount in the control group than in the bevacizumab group (p=0.047). Overall survival was not statistically different between both groups.ConclusionThese initial data demonstrate that MCR can be performed safely after triple induction chemotherapy with bevacizumab without increased intra- and postoperative bleeding complications. Response rates were significantly improved by the addition of bevacizumab.

High-dose methotrexate monotherapy for newly diagnosed primary central nervous system lymphoma: 15-year multicenter experience.

Primary central nervous system lymphoma (PCNSL) is rare disease and shows poor prognosis although methotrexate-based chemotherapy is used. Here, we present our experiences with high-dose methotrexate (HD-MTX) monotherapy for immunocompetent patients with PCNSL at three institutions and investigate factors related to survival. PCNSL patients, who were histologically confirmed with diffuse large B cells and treated with HD-MTX monotherapy from 2001 to 2016, were retrospectively reviewed. Patients underwent induction chemotherapy with 8g/m2 of MTX every 10 days (maximum three cycles). Maintenance chemotherapy of 3.5g/m2 of MTX (maximum six cycles) was selectively performed depending on the response to induction chemotherapy. A total of 67 patients were included. Although seven patients discontinued induction chemotherapy because of MTX toxicity, 40 (59.7%) patients showed a complete response (CR) to induction chemotherapy. Twenty-six (38.8%) and three (4.5%) patients showed a CR and partial response, respectively, after maintenance chemotherapy. Forty-one patients with recurrence or progression following HD-MTX underwent second-line treatment. Progression-free survival rates were 43% and 24% at 1 and 2 years, respectively. The median overall survival was 40.3 months. In a multivariate analysis, a radiological CR to induction chemotherapy was a significant factor related to prolonged progression-free survival and overall survival (P<0.05). MTX-monotherapy is tolerable in terms of adverse effects and still considered as a treatment option in patients with PCNSL. However, an additional therapeutic option should be prepared for non-CR responders to induction chemotherapy.

Infection at diagnosis-a unique challenge in acute myeloid leukemia treatment in developing world.

A large number of AML patients present with infection at the time of initial presentation in Indian settings. There is lack of published data on the proportion of patients with infection at initial presentation and its impact on induction mortality. A retrospective audit of patients with newly diagnosed AML more than 14years of age, who underwent standard induction chemotherapy between the periods of January 2011 to December 2018, was done. Infection at presentation if any was documented. Induction mortality was defined as death happening within 28days of starting induction chemotherapy. Among a total of 315 cases of AML, 96 (30%) patients underwent induction chemotherapy with 7 + 3 regimen. Documented infection at baseline was present in 30 (31%) of patients. Another 10 patients had fever at the time of presentation but without any documented infection focus. Fifteen patients died within 4weeks of induction amounting to induction mortality of 15.6%. Induction mortality was 28% among patients with infection at baseline compared with 7% without baseline infections (P = 0.01). Around 40% of patients had fever at the time of presentation, and 31% had documented infections. Baseline infections led to increase in induction mortality. We would like to propose that infection at baseline is to be considered as one of the potential variables in the predictive scoring system for induction mortality in developing countries.

Outcomes of patients with initially locally advanced pancreatic adenocarcinoma who did not benefit from resection: a prospective cohort study

BackgroundThe current study aimed to evaluate the outcomes of patients with unresectable non-metastatic locally advanced pancreatic adenocarcinoma (LAPA) who did not benefit from resection considering the treatment strategy in the clinical settings.MethodsBetween 2010 and 2017, a total of 234 patients underwent induction chemotherapy for LAPA that could not be treated with surgery. After oncologic restaging, continuous chemotherapy or chemoradiation (CRT) was decided for patients without metastatic disease. The Kaplan–Meier method was used to determine overall survival (OS), and the Wilcoxon test to compare survival curves. Multivariate analysis was performed using the stepwise logistic regression method.ResultsFOLFIRINOX was the most common induction regimen (168 patients, 72%), with a median of 6 chemotherapy cycles and resulted in higher OS, compared to gemcitabine (19 vs. 16 months, hazard ratio (HR) = 1.2, 95% confidence interval: 0.86–1.6, P = .03). However, no difference was observed after adjusting for age (≤75 years) and performance status score (0–1). At restaging, 187 patients (80%) had non-metastatic disease: CRT was administered to 126 patients (67%) while chemotherapy was continued in 61 (33%). Patients who received CRT had characteristics comparable to those who continued with chemotherapy, with similar OS. They also had longer progression-free survival (median 13.3 vs. 9.6 months, HR = 1.38, 95% confidence interval: 1–1.9, P < .01) and limited short-term treatment-related toxicity.ConclusionsThe median survival of patients who could not undergo surgery was 19 months. Hence, CRT should not be eliminated as a treatment option and may be useful as a part of optimised sequential chemotherapy for both local and metastatic disease.

Lung cancer surgery in oligometastatic patients: outcome and survival.

A few studies have already demonstrated survival benefits for local treatment in solitary metastatic non-small-cell lung cancer (NSCLC). The aim of this study is to retrospectively investigate the role of surgery in patients with oligometastatic (OM) NSCLC. Between January 1998 and December 2018, 57 patients with OM stage IV NSCLC (1 or 2) underwent a multidisciplinary approach including lung cancer surgery, local treatment of the distant metastasis (DM) and systemic medical treatments. All patients had DM synchronous to lung cancer. Fifty-one (90%) patients had a single DM whereas 6 (11%) patients had 2 DMs. Forty-eight (84%) patients underwent induction chemotherapy. We performed 47 (82%) lobectomies, 4 (7%) segmentectomies and 6 (11%) pneumonectomies. Pathological lymph node involvement was evident in 28 (49%) patients. Adjuvant chemotherapy was administered in 20 (35%) patients. Forty-six (81%) patients had local treatment of the DM before lung resection, and 11 (19%) patients had after lung resection; 6 (11%) patients had both treatments. The median overall survival (OS) was 30 months, with the 2-, 3- and 5-year OS of 57%, 50% and 30%, respectively. OS was significantly related to lymph node involvement (P = 0.04), size of the primary tumour (P < 0.001), neoadjuvant chemotherapy (P = 0.02) and the time period between metastasis diagnosis and primary tumour removal (P = 0.04). Multidisciplinary approach is the gold standard in OM patients. Patients with no lymph node involvement are the best candidates, with an acceptable OS. Thus, patients with OM-NSCLC should not be excluded from surgery as a matter of principle.

Sporadic Late Onset Nemaline Myopathy with a Monoclonal Gammopathy: Comparative Effectiveness of Immuno- and Chemotherapy

Introduction A rare subset of sporadic late-onset nemaline myopathy (SLONM) is associated with monoclonal gammopathy of unknown significance (MGUS). The role of monoclonal protein (M-protein) in SLONM is unknown, but SLONM with MGUS (SLONM+MGUS) demonstrates an aggressive disease course with severe muscular weakness, early development of respiratory failure, and is often fatal. Whether SLONM+MGUS represents a malignant or dysimmune disease remains unclear. Currently, two approaches are used to treat SLONM+MGUS: 1) immunosuppression ± plasmapheresis/exchange; or 2) chemotherapy (ChT) ± autologous stem cell transplantation (ASCT). Unfortunately, due to the rare occurrence of the disease, the best treatment modality is unknown. Methods We conducted a literature search to identify previous treatment modalities for patients diagnosed with SLONM+MGUS using PubMed, Elsevier, Medline, and CINAHL databases from 1975 to 2019. All publications were carefully reviewed to remove "duplicate" patients. Overall, 28 reports were included for the final analysis. Results We identified 38 unique patients diagnosed with SLONM+MGUS treated either with immunotherapy (IT) (n=19) or ChT ± ASCT (n=19). The median age was 49 years [range: 26-75] in the IT group and 47 years [range: 24-64] in the ChT group. There was a slight male preponderance in the IT group [n=14 (74%)] than in the ChT group [n=10 (53%)]. Similarly, more cases with kappa light chain restricted M-protein were observed in the IT group [n=12 (67%)] than in the ChT group [n=8 (42%)]. In the IT group, M-protein values were only reported in two patients (mean: 0.42 g/L), while M-protein values were reported for 14 patients in the ChT group (mean: 6.54 g/L). In the IT group 16 patients (84%) received steroids, 5 (26%) plasmapheresis, 10 (53%) steroid-sparing immunosuppressants (low dose cyclophosphamide, azathioprine, cytarabine, and mycophenolate mofetil), 2 (11%) rituximab, and 10 (53%) IVIG. Twelve (63%) patients received oral prednisone (mean dose: 67 mg) and 3 (16%) received pulse methylprednisolone (1 g). Patients received IT modalities sequentially or in parallel. Six patients (32%) received 1 and 13 patients (68%) received 2 or 3 (median = 2) IT types. Neurological improvement was observed in 10 patients, a 53% overall response rate (ORR) with 3 (16%) patients in complete remission (CR), and 7 (37%) patients in partial response (PR). No improvement or progression was observed in 9 (47%) patients (Figure 1). In 2 patients, neurological CR was associated with complete disappearance of M-protein. Mean time to best response was 19 months in a follow-up duration of 23 months. The ChT group included three categories: 1) 10 (53%) patients received ASCT with high dose melphalan (mean: 164 mg/m2); 2) 3 patients (16%) were treated with Cyclophosphamide/Bortezomib/Dexamethasone (CyBorD), cyclophosphamide/Thalidomide/Dexamethasone and Lenalidomide and Dexamethasone (Ld) chemotherapy without ASCT; and 3) 6 (31%) patients underwent induction chemotherapy with CyBorD (n=2) and Ld (n=4), followed by consolidative ASCT. Neurological improvement was achieved in 18 patients, a 94.7% ORR with CR in 14 (73.7%) and PR in 3 (21.0%) patients. Only one patient did not respond to therapy. The best neurological improvement correlated with disappearance of M-protein [complete hematological remission (CHR)]. Mean time to best response was 10 months, which was shorter than the IT group. Follow-up duration was 31 months. Conclusion Based on a comprehensive evaluation of existing treatment modalities for patients with SLOMN+MGUS we conclude that the best course of treatment is through consideration of the disease as a malignancy rather than a dysimmune disease. Our review supports that the best method of treatment entails ChT with or without of consolidative ASCT in the pursuit of eliminating the malignant plasma cell clone. In conjunction with nemaline myopathy presence of M-protein has clinical significance and it may be worth considering reclassifying SLONM+MGUS as SLONM with Monoclonal Gammopathy of Clinical (Neurological) Significance (SLONM+MGCS). Disclosures No relevant conflicts of interest to declare.

Radical accelerated radiotherapy for non-small cell lung cancer (NSCLC): A 5-year retrospective review of two dose fractionation schedules

Background and purposeNumerous fractionation regimes are used for inoperable NSCLC patients not suitable for stereotactic ablative radiotherapy. Continuous hyperfractionated accelerated radiotherapy (CHART, 54 Gy, 36 fractions over 12 days) and hypofractionated accelerated radiotherapy (55 Gy, 20 fractions over 4 weeks) are recommended UK schedules. In this single-centre retrospective analysis, we compare both fractionation schemes for patients treated at our institution from 2010 to 15. Materials and methodsClinical demographic, tumour and survival data were collected alongside radiotherapy dosimetric data from the Varian Eclipse Scripting application programming interface. Differences were assessed using independent samples t-tests. Multivariate survival analysis was performed using Cox regression. ResultsWe identified 563 eligible patients; 43% received CHART and 57% hypofractionated radiotherapy. Median age was 71 years, 56% were male, 95% PET staged with 53% WHO performance status 0–1. 30%, 14%, 50% and 6% were stage I, II, III and IV, respectively. 38% of patients underwent induction chemotherapy. 99% completed their prescribed radiotherapy treatment. Overall response rate was 50% with a 6.5% 90-day mortality rate. Median disease-free survival was 19 months, 50% recurred locally. Median overall survival was 22.5 months with 48% alive at 2 years. Multivariate analysis identified histology, stage, performance status, chemotherapy and radiotherapy response as independent predictors of survival; no significant differences between radiotherapy regimes were observed. ConclusionIn our centre, CHART and hypofractionated accelerated radiotherapy produce similar outcomes. Dose escalation studies are in progress to develop these schedules to match outcomes reported in concurrent chemo-radiation studies.

PB1937 CHROMOSOMAL ABERRATIONS IN CHRONIC MYELOID LEUKEMIA AND THEIR IMPACT ON RESPONSE TO CONVENTIONAL TYROSINE KINASE INHIBITORS AND RISK OF BLASTIC TRANSFORMATION.

Background:Chronic Myeloid Leukemia(CML) is a common hematological malignancy with tyrosine kinase inhibitors(TKI) forming the main stay of treatment.Aims:The purpose of this project was to study the clinical presentation of patients with CML harboring additional chromosomal abnormalities at diagnosis and disease outcomes.Methods:This is a retrospective chart review of all patients who were diagnosed with CML in chronic phase (CP) with additional chromosomal abnormalities (ACAs) over a period of 5 years from 2010 to 2015 at our institution.Results:Response to initial TKI A total of 283 patients were diagnosed with CML from January 2010 to January 2015. Thirty one patients were found to have ACAs at the time of diagnosis in addition to BCR‐ABL fusion gene.23 patients (74.2%) were males whereas 8(25.8%) were females. 13(41.9%) were in the age group of 31 to 50 years. 30 patients were started on Imatinib and one on Nilotinib. 16 patients (51.6%) achieved complete hematological response within 3 months. However a complete molecular and cytogenetic response was never achieved in 17 (54.8%) and 18 (58.1%) patients respectively.Cytogenetics Analysis and ACAs Conventional cytogenetic analysis revealed that 11 (35.5%) of patients had variant Philadelphia chromosome followed by 7 patients (22.6%) with trisomy 8. 5 patients (16.1%) had multiple chromosomal abnormalities including trisomy 8, deletion 1 and isochrome 17q.Risk of blastic transformation Eight patients (25.8%) transformed to acute myeloid leukemia(AML) whereas 3 (9.7%) patients had a transformation to acute lymphoblastic leukemia(ALL).Therapy and response in transformed patients Out of the 11 patients who transformed to AML and ALL, 6 patients underwent induction chemotherapy while 5 were not considered fit for it on account of poor performance score and lack of resources. Out of these 6 patients, none responded to induction chemo.Summary/Conclusion:In summary, this study aimed to look at the clinical presentation of patients with CML harboring additional chromosomal abnormalities at diagnosis, cytogenetic analysis, risk of blastic transformation and response to treatment in transformed patients. Despite an early hematological response, more than half of the patients failed to achieve complete molecular and cytogenetic response which clearly shows suboptimal response to the tyrosine kinase inhibitors in this particular set of CML patients. There was transformation to acute leukemia in 35.5% of patients. We were able to give induction chemotherapy to only 6 out of 11 patients and none of them responded to it. This study showed that presence of ACA at the time of diagnosis is a high risk feature for patients with CML and confers poor prognosis when treated with conventional TKI. Further studies are required in our population regarding alternative therapy for such patient population.

PB1668 EARLY T‐CELL PRECURSOR (ETP) ACUTE LYMPHOBLASTIC LEUKEMIA (ETP‐ALL) IN ADOLESCENTS AND ADULTS: A HIGH‐RISK SUBTYPE

Background:Early T‐cell precursor (ETP) acute lymphoblastic leukemia/lymphoma (ALL/LBL) is recognized as high‐risk T‐ALL/LBL subgroup. The optimal therapeutic approached to adult patients with ETP‐ALL/LBL not well characterized.Aims:In this study, we compared the outcomes of adults with ETP‐ALL receiving treatment with frontline regimes to those with other T‐ALL immunophenotypic subtypes.Methods:This is a 10 years retrospective analytical study of adult patient diagnosed with T‐ALL. Patients with newly‐diagnosed T‐ALL/LBL receiving frontline chemotherapy between the years of 2008‐2018 at Ampang Hospital, Malaysia were identified and immunophenotypically categorized into TI(pro‐T), T‐II(pre‐T), T‐III (cortical‐T) and T‐IV(mature‐T) as per European Group for the Immunological Characterization of Leukaemia (EGIL) classification using CD1a and cytoplasmic/surface CD3. Overall survival (OS) was analysed using Kaplan‐Meier survival function and different groups were compared using log‐rank test. Event‐free survival (EFS) was calculated from the time of CR until relapse or death.Results:A total of 77 patients with T‐ALL were identified with adequate immunophenotype data. Of the 77 patients, only 60 could be subtyped into Pro‐T (6.7%), Pre‐T (21.7%), Cortical‐T (6.7%), Mature T (23.3%) and ETP (41.7%) subtypes, largely due to discordant expression of differentiation markers that do not conform to this immunophenotypic classification scheme. The ETP‐ALL group had a median age of 29 years, compared to non‐ETP which was 25 years. Among these subtype T‐ALL, 71.7% (n = 43) were age of 35 and above, and 28.3% (n = 17) were below age of 35. There was male predominance (76.7%). Patients were mainly Malay (58.3%), followed by Chinese (21.7%) and Indian (16.7%), with the remaining 3.3% of other racial origins. There was no significant association between total white count (TWC) at presentation and ALL subtypes (ETP vs non‐ETP) using cut‐off of 100 TWC (χ2 = 1.34, df = 1, p = 0.248). This cohort presented median overall survival (OS) of 13 month (95%CI: 9.4; 18.0) and median event free survival (EFS) of 10 month (95%CI: 6.6; 16.4). The majority of patients underwent induction chemotherapy with curative intent (95%, n = 60)whereas 5%(n = 3) were upfront palliative intent. The induction chemotherapy were mainly GMALL or HyperCVAD (93%, n = 57) where less than 10% were BLOCK and BFM (5.3% and 1.8%, n = 6). Median OS and EFS were further evaluated and we found no significant difference among patients of different subtypes, TWC (cut‐off = 100). However, among these factors, TWC appeared to be a potential predictor for OS due to marginal p‐value to 0.05.Summary/Conclusion:ETP‐ALL/LBL represents a high‐risk disease subtype of adult ALL. Novel treatment strategies are needed to improve treatment outcomes of this T‐ALL/LBL subset.

Role of induction chemotherapy in sinonasal malignancies: a systematic review.

Cancers of the paranasal sinuses are rare tumors that tend to be aggressive and usually are diagnosed at an advanced stage. Despite being rare, these tumors include a wide spectrum of histological subtypes with different biological behaviors. Choosing the optimal treatment modalities and analyzing the different oncological outcomes is therefore challenging. This study aims to evaluate the role of induction chemotherapy prior to definitive local therapy for sinonasal malignancies. A systematic review of the literature in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted. With the assistance of a medical librarian, data sources including MEDLINE, PubMed, Cochrane library, EMBASE, NCBI Bookshelf, National Guideline Clearinghouse, and Clinicaltrials.gov were searched using a customized search strategy that yielded 1758 articles. Inclusion criteria used were as follows: (1) the study has a patient population with 3 or more patients with previously untreated sinonasal malignancies; (2) patients underwent induction chemotherapy prior to definitive local therapy; (3) pretreatment staging information was documented; (4) overall survival was reported by histology type either in table or Kaplan-Meier format. Nine studies with 220 patients ultimately met inclusion criteria and were analyzed in groups based on tumor histology. For squamous cell carcinoma (SCC), the 5-year overall survival was 51%. For neuroendocrine tumors, the 5-year overall survival was 78%. Eighteen percent (18%) of patients with pretreatment orbital involvement ultimately underwent orbital exenteration. Induction chemotherapy in the management of sinonasal malignancies has similar overall survival outcomes as other standard treatment modalities and can be offered as an option to patients as part of multimodality therapy.