stage-IV Disease Research Articles

Impact of 18FDG PET/CT on Clinical Management, Cost Effectiveness, and Radiation Exposure in Newly Diagnosed Breast Cancer Patients.

For the initial staging of breast cancer (BC), 18FDG PET/CT is recommended by professional guidelines in stage III (except T3N1) and inflammatory BC (T4d) and optional when conventional imaging is equivocal or suspicious. However, growing evidence also supports its role in the staging of intermediate-risk groups (IIA, IIB, T3N1 of IA). This study aimed to compare the impact of 18FDG PET/CT with conventional imaging (CT-chest+abdomen+pelvis and bone scan; CT-CAP+BS) in staging, cost-effectiveness, and radiation exposure in the initial staging of BC. A retrospective study (April 2020 2024) included 115 biopsy-proven BC patients who had CT-CAP+BS and 18FDG PET/CT for initial staging. Data were analyzed to see the impact of 18FDG PET/CT on change in staging, cost-effectiveness, and radiation exposure compared to CA-CAP+BS. Out of 115 patients (113 female and 02 male), 110 had unilateral and 5 had bilateral BC (Invasive Ductal Ca. 107; Non-IDC: 08) with non-significant laterality. The overall upstaging rate for regional nodal and/or distant metastases was 36% (24/66; excluded 49 with stage IV). The overall upstaging rate due to unsuspected higher nodal metastases was 20% (predominantly stage IIA, and IIB). Upstaging rate to stage IV was seen in 17% (11/66; predominantly in IIIA-C). The overall concordance (no change in staging) was seen in 64% (42/66) while no downstaging was found in any patient. In patients with stage-IV disease (n = 49), 18FDG PET/CT identified a higher number of hypermetabolic lesions in 18 (37%), lesser in 07 (14%), and similar in 24 (49%) cases. The estimated cost in Pak rupees for CT-CAP+BS and PET/CT was 139000 and 106000 respectively. The mean effective dose imparted by 18FDG PET/CT was 8.85 mSv compared to the reported 26.6 mSv by CT-CAP+BS. We conclude that in the initial staging of BC, 18FDG PET/CT compared with CT-CAP+BS has a significant impact on decision-making by upstaging the disease in stage II and III and detecting more metastatic lesions in stage-IV disease. Furthermore, 18FDG PET/CT is more cost-effective and imparts significantly lower radiation exposure as compared with CT+CAP+BS. These findings support the inclusion of 18FDG PET/CT in the initial staging of stage II-IV BC.

Phase angle is a predictor of overall 5-year survival after head and neck cancer surgery

ObjectiveTo evaluate the ability of the variables Muscle Mass percentage (%MM), Body Fat percentage (%BF), Phase Angle (PhA), and Standardized Phase Angle (SPhA) to predict overall survival rates in individuals with surgically treated HNC. MethodsA prospective cohort study of surgically treated HNC patients was carried out between 2017 and 2022 at a cancer referral center in Feira de Santana, Bahia. All subjects were seen by an experienced dietitian the week before surgery. During this visit, patients had their sociodemographic and clinical data collected, as well as anthropometric measurements (weight and height) and BIA variables. In this study, postoperative overall 5-year survival was defined as the time in months between the date of surgery and the date of death, regardless of the cause of death. Patients were followed up after surgery until death. ResultsSeventy-eight older adult patients were consecutively included. Patients had a median age of 65.5-years, were mostly men (83.3%), and most had low education levels (62.3%) and low household income, ranging from zero (19.2%) to the minimum wage (60.2%). They were mostly alcohol drinkers (91%) and tobacco smokers (87.2%). Glottic cancer was diagnosed in 48.7% of patients, with 44.8% of cases with stage-IV disease. Forty (51.2%) deaths were recorded in the follow-up period, with a median survival time of 39 months. Variables %MM, %BF, and SPhA were not significantly different between groups (alive vs. dead patients). PhA was considered an independent predictor of overall survival, with an accuracy of 69% (95% CI 0.57‒0.80). When comparing survival curves, patients with a preoperative PhA < 6.8° were more than twice as likely to die during follow-up (HR = 2.38; p = 0.02; 95% CI 1.14‒4.97). ConclusionOut of the assessed BIA variables, preoperative PhA was considered a good predictor of overall survival after HNC surgery. Level of evidence3.

A retrospective analysis of efficacy and safety of lenvatinib combined with PD-1 inhibitor and chemotherapy in advanced biliary tract cancer (BTC).

e16173 Background: Lenvatinib combined with PD-1 inhibitor and chemotherapy has showed a relatively high antitumor activity for ICC in phase 2 clinical trials. This study retrospectively analyzes the efficacy and safety of real-world lenvatinib combined with PD-1 inhibitor and chemotherapy in BTC. Methods: Patients with advanced BTC who received lenvatinib combined with PD-1 inhibitor plus oxaliplatin and gemcitabine (Gemox) chemotherapy were retrospectively screened. The overall survival, progression-free survival, objective response rate, disease control rate and safety were evaluated. Results: From Jan 2021 to Apr 2023, 27 pathologically-confirmed advanced BTC pts were enrolled. The median age is 61 (range, 39-74) years, 18 (66.7%) were male. Fourteen patients had TNM stage Ⅳdisease, and 7 patients had stage III. Twenty-six (96.3%) patients had an ECOG performance status of 1. All patients were child-pugh A. Fourteen patients had metastasis, 8 patients with lymph node metastasis, 4 with bone metastasis. 11 (40.7%) had positive PD-L1 expression. At baseline, 18 (66.7%) patients had a CA19-9 level &gt; 200 U/mL. The median CEA level was 3.56 ng/mL; 48.1% of the patients had a level &gt; 5 ng/mL. At the date cut off (Dec 15, 2023), the median follow-up time was 10.4 months (range: 4.8-25.7). ORR was 70.4% (19/27), and disease control rate (DCR) was 85.2% (23/27). Three pts with locally advanced disease were down-staged and then underwent resection. They remained disease-free survival at the end of last follow-up. The median PFS was 9.0 months (95% CI: 4.0-14.0) and median duration of response (DOR) was 9.8 months. The median OS was 20.4 months (95% CI: 13.6-27.2). 12-months OS rate was 73.3% (95% CI: 57.5%-89.2%).20/27 pts experienced treatment-related adverse events (AE). No grade 5 AE was observed. The most common AE was fatigue 66.7% (18/27), headache 7.4% (2/27). Grade 3 fatigue and grade 3 kidney injury occurred in 1 patient separately. Conclusions: Lenvatinib combined with PD-1 inhibitor and Gemox chemotherapy provided remarkable efficacy with reasonable tolerability in advanced BTC patients.

Reduced chemokine C-C motif ligand 1 expression may negatively regulate colorectal cancer progression at liver metastatic sites.

Colorectal cancer (CRC) liver metastasis, albeit a stage-IV disease, is completely curable by surgical resection in selected patients. In addressing the molecular basics of this phenomenon, differentially expressed genes at primary and liver metastatic sites were screened by RNA sequencing with the use of paraffin-embedded surgical specimens. Chemokine C-C motif ligand 1 (CCL1), a chemotactic factor for a ligand of the chemokine C-C motif receptor 8 (CCR8), was isolated as one of the differentially expressed genes. Histological analysis revealed that the number of CCL1-positive cells, mainly tumour associated macrophages (TAMs) located in the stroma of CRC, decreased significantly at liver metastatic sites, while the expression level of CCR8 on CRC remained unchanged. To explore the biological significance of the CCL1-CCR8 axis in CRC, CCR8-positive CRC cell line Colo320DM was used to assess the effect of the CCL1-CCR8 axis on major signalling pathways, epithelial mesenchymal transition induction and cell motility. Upon stimulation of recombinant CCL1 (rCCL1), phosphorylation of AKT was observed in Colo320DM cells; on the other hand, the corresponding significant increase in MMP-2 levels demonstrated by RT-qPCR was nullified by siRNA (siCCR8). In the scratch test, rCCL1 treatment significantly increased the motility of Colo320DM cells, which was similarly nullified by siCCR8. Thus, the activation of the CCL1-CCR8 axis is a positive regulator of CRC tumour progression. Reduced CCL1 expression of TAMs at liver metastatic sites may partly explain the unique slow tumour progression of CRC, thus providing for a grace period for radical resection of metastatic lesions.

Sidedness is not a prognostic factor in an unselected cohort of patients with colon cancer but prognosis for caecal carcinoma is worse – A multivariate analysis of a large single institution database

PurposeSidedness has emerged as a prognostic factor for metastatic colorectal cancer treated with modern systemic therapies. This study investigates whether it is also relevant for an unselected patient cohort including all stages.MethodsAll consecutive patients admitted with colon cancer between 1995 and 2018 were retrieved from an institution-held database. Patients were divided into two cohorts. The first cohort included patients without distant metastases who were able to undergo curative resection. The second cohort presented with distant metastases (stage IV). Potentially prognostic factors were subjected to multivariate Cox Regression analysis.ResultsOverall, 1,606 patients met the inclusion and exclusion criteria. An R0-resection was achieved in 1,222 patients without distant metastases. Five-year cause-specific survival rate was 89.3% for this group. There was no difference between right- and left-sided cancers (88.2% vs. 90.1%, p = 0.220). However, prognosis of caecal carcinoma was significantly worse than that of all other sites combined (83.5% vs. 90.2%, p = 0.007). In multivariate analysis, pT-category, pN-category, grading, vascular invasion, emergency operation, adjuvant chemotherapy, and caecal carcinoma remained as independent prognostic factors. In the 384 patients with stage IV-disease, 3-year overall survival for right- vs. left-sided cancers differed only in univariate analysis (17.7% vs. 28.6%, p = 0.013).ConclusionIn non-metastatic colon cancer, location in the caecum is an independent prognostic factor. In unselected patients with stage IV colon cancer, sidedness was not found to be a prognostic factor. Differentiation into right- and left-sided tumors may be simplistic, and further studies on the biological behavior of different colonic sites are warranted.

Translated article] Cost of Treating Cutaneous T-Cell Lymphoma in Spain: Analysis of MICADOS Study Data by Disease Stage

Background and objectiveThe cost of treating cutaneous T-cell lymphoma (CTCL) in Spain is unknown. With the advent of new treatments, it is more important than ever to gain an accurate picture of the true costs involved. The MICADOS study had 2 primary objectives: 1)to evaluate the impact of CTCL on patient quality of life, and 2)to evaluate the costs associated with the disease. This article reports the results of the cost analysis. MethodsWe estimated the cost of treating CTCL over a period of 1year from the perspective of the Spanish National Health System. Twenty-three dermatologists and hematologists from 15 public hospitals analyzed data for adult patients with mycosis fungoides (MF) or Sézary syndrome (SS). ResultsA total of 141 patients (57.4% male) with a mean age of 63.6 years (95%CI: 61.4-65.7 years) were included. The mean direct annual cost of treating CTCL was €34,214 per patient. The corresponding costs by stage were €11,952.47 for stageI disease, €23,506.21 for stageII disease, €38,771.81 for stageIII disease, and €72,748.84 for stageIV disease. The total direct annual cost of treating MF/SS in public hospitals in Spain was estimated at €78,301,171; stageI disease accounted for 81% of all costs, stageII for 7%, and stagesIII andIV for 6% each. ConclusionsThe MICADOS study offers an accurate picture of the direct cost of treating CTCL in patients with MF/SS in Spain and shows that costs vary significantly according to disease stage. Patient-borne and indirect costs should be analyzed in future studies.

Evaluación de los costes asociados a la enfermedad de pacientes con linfoma cutáneo de células T en España: análisis en función del estadio clínico (estudio MICADOS)

Background and objectiveThe cost of treating cutaneous T-cell lymphoma (CTCL) in Spain is unknown. With the advent of new treatments, it is more important than ever to gain an accurate picture of the true costs involved. The MICADOS study had 2 primary objectives: 1)to evaluate the impact of CTCL on patient quality of life, and 2)to evaluate the costs associated with the disease. This article reports the results of the cost analysis. MethodsWe estimated the cost of treating CTCL over a period of 1year from the perspective of the Spanish National Health System. Twenty-three dermatologists and hematologists from 15 public hospitals analyzed data for adult patients with mycosis fungoides (MF) or Sézary syndrome (SS). ResultsA total of 141 patients (57.4% male) with a mean age of 63.6 years (95%CI: 61.4-65.7 years) were included. The mean direct annual cost of treating CTCL was €34,214 per patient. The corresponding costs by stage were €11,952.47 for stageI disease, €23,506.21 for stageII disease, €38,771.81 for stageIII disease, and €72,748.84 for stageIV disease. The total direct annual cost of treating MF/SS in public hospitals in Spain was estimated at €78,301,171; stageI disease accounted for 81% of all costs, stageII for 7%, and stagesIII andIV for 6% each. ConclusionsThe MICADOS study offers an accurate picture of the direct cost of treating CTCL in patients with MF/SS in Spain and shows that costs vary significantly according to disease stage. Patient-borne and indirect costs should be analyzed in future studies.

Patient Characteristics, Testing and Treatment Patterns, and Outcomes in EGFR-Mutated Advanced Non-Small Cell Lung Cancer: A Multinational, Real-World Study.

Treatment landscape for advanced/metastatic NSCLC (aNSCLC) has evolved considerably over the past few decades with the advent of targeted therapies for epidermal growth factor receptor-mutated (EGFRm+) aNSCLC treatment. This study described real-world patient and disease characteristics, treatment and practice patterns, and clinical, economic, and patient-reported outcomes (PROs) in patients with EGFRm+ aNSCLC. Data were derived from the Adelphi NSCLC Disease Specific Programme™ (DSP™), a point-in-time survey conducted between July and December 2020. The survey included oncologists and pulmonologists, and their consulting patients (with physician-confirmed EGFRm+ aNSCLC) from nine countries: the US, Brazil, theUK, Italy, France, Spain, Germany, Japan, and Taiwan. All analyses were descriptive. Overall, 542 physicians reported data for 2857 patients (mean age 65.6years), and most patients were female (56.0%), white (61.0%), and had stageIV disease at initial diagnosis (76.0%), and adenocarcinoma histology (89.0%). Most patients received EGFR-tyrosine kinase inhibitors (TKI) therapy in first- (91.0%), second- (74.0%), and third-line (67.0%). The most common tumor samples and methods for EGFR detection were EGFR-specific mutation detection tests (44.0%) and core needle biopsy (56.0%). Median time to next treatment was 14.0 (IQR 8.0-22.0) months and disease progression was the main physician-reported reason for early discontinuation. The most common physician-reported disease symptoms were cough (51.0%), fatigue (37.0%), and dyspnea (33.0%). In patients assessed for PROs, mean EQ-5D-5L index and FACT-L health utility scores were 0.71 and 83.5, respectively. On average, patients lost 10.6h of work/week for approximately 29.2weeks due to EGFRm+ aNSCLC. This real-world multinational dataset showed that most patients with EGFRm+ aNSCLC were treated per the country relevant clinical guidelines, with progression as the main reason for early treatment discontinuation. For the included countries, these findings may offer a useful benchmark for decision makers to determine future allocation of healthcare resources for patients with EGFRm+ aNSCLC.

Real-World Outcomes Following First-Line Treatment in Patients with Advanced Ovarian Cancer with Multiple Risk Factors for Disease Progression who Received Maintenance Therapy or Active Surveillance.

We evaluated real-world outcomes in patients with advanced ovarian cancer (AOC) based on their cumulative risk profile and maintenance therapy (MT) status following first-line (1L) treatment. This retrospective observational study of a nationwide electronic health record-derived de-identified database included adult patients diagnosed with stageIII/IV OC from January1, 2011 to February28, 2021, who received 1L therapy and had ≥ 12weeks of follow-up after the index date (end of 1L therapy). Patients were grouped according to whether they received MT or active surveillance (AS) following 1L treatment and by the cumulative number of risk factors (RF) present (stageIV disease; no surgery/treated with neoadjuvant therapy and interval debulking surgery; had postoperative visible residual disease; and had BRCA wild-type disease/unknown BRCA status). Time to next treatment (TTNT) and overall survival (OS) were assessed with a cloning and inverse probability of censoring (IPC)-weighted Kaplan-Meier method. Among 1920 patients, 22.2% received MT and 77.8% received AS. Median IPC-weighted TTNT and OS were 13.3months (95%CI 11.7-15.8) and 39.1months (95%CI 32.5-48.6) in the MT cohort, respectively, and 8.6months (95%CI 8.0-9.5) and 38.4months (95%CI 36.4-41.0) in the AS cohort, respectively. Almost all patients had ≥ 1 RF (MT 95.3%; AS 96.7%). Median IPC-weighted TTNT was shorter among patients with more RF in both cohorts (MT: 1RF, 19.3months, 95%CI 13.5-37.8; 2RF, 17.2months, 95%CI 12.8-20.2; 3RF, 11.0months, 95%CI 8.2-13.8; 4RF, 7.0months, 95%CI 6.2-8.8; AS: 1RF, 17.7months, 95%CI 13.5-22.3; 2RF, 10.2months, 95%CI 9.1-11.5; 3RF, 6.5months, 95%CI 5.8-7.4; 4RF, 4.1months, 95%CI 3.5-4.5). Regardless of RF number, MT was associated with longer TTNT in real-world patients with AOC.

Comparison of characteristics and outcomes of young-onset versus average onset pancreatico-biliary adenocarcinoma.

Young-onset gastrointestinal malignancies appear to be increasing in incidence. There are limited data on young-onset pancreaticobiliary adenocarcinoma (YO-PBA). The study comprised patients with PBA (pancreatic adenocarcinoma, intra-, and extra-hepatic cholangiocarcinoma) and included in the National Cancer Database (NCDB) between 2004 and 2017. YO-PBA was defined as a diagnosis at age less than 50 years. Logistic regression to assess factors associated with YO-PBA status, and cox proportional hazards modeling to associate relevant factors with overall survival was performed. The study cohort comprised 360,764 patients, with 20,822 (5.8%) YO-PBA. YO-PBA was associated with (p-values<0.0001 for all): male sex (6.3% YO-male out of all male patients vs. 5.2% YO-female, OR 1.29, 95% CI 1.25-1.33), Black race (7.9% YO-Black vs. 5.0% YO-White, OR 1.72, 95% CI 1.64-1.80), lower income (6.4% YO-lowest household income based group vs. 5.5% highest, OR 1.08, 95% CI 1.03-1.13). YO-PBA were more likely to present with stage-IV disease (6.4% YO-Stage IV of all stage IV vs. 5.4% YO-Stage I-III, OR 1.25, 95% CI 1.21-1.29 p-value < 0.0001). Factors associated with overall survival (OS) in non-operable patients included-sex - male vs. female, HR 1.12 (95% CI 1.08-1.15); race - Black vs. White, HR 1.23 (95% CI 1.06-1.42); income group - lowest vs. highest, HR 1.33 (95% CI 1.27-1.39), and treatment center type - academic vs. nonacademic center, HR 0.87 (95% CI 0.85-0.90). Socioeconomic factors significantly impact incidence and outcomes for young-onset pancreaticobiliary adenocarcinoma (YO-PBA). More work is needed to help understand the mechanisms involved while addressing the disparities.

Avascular Necrosis of Femoral Head: A Retrospective Study of MRI Scan in A Orthopedic Hospital

Background : Avascular necrosis (AVN), also known as osteonecrosis of femoral head is a pathology in which many etiologies play role and cause decreased vascular supply to subchondral bone of femoral head which results in osteocyte death. MRI is the most sensitive modality for detection of AVN and is helpful for screening and detecting at early stage. Purpose: The aim of the study was to determine the prevalence pattern and stages of presentation of Avascular Necrosis (AVN) of the femoral head. Materials and Methods: This was a retrospective study carried out at the department of Radiology &amp; Imaging, National Institute of Traumatology &amp; Orthopedic Rehabilitation (NITOR), Dhaka where MRI of the hip joint was performed during our study period, only those patients which showed positive signs for avascular necrosis of femoral head were included and were analysed over a period of five years. The age, sex, laterally distribution, causative factors, staging according to Ficat and Arlet classification was done. Results: It was found that most commonly males of productive age group (21 to 40 years) were affected. Though most of them had unilateral involvement however number of bilateral cases were also significant. Mostly, patient presented with stage-IV disease accounting for 104 out of 152 patients (68.42%). Conclusion: Considering that the young males were commonly affected and presented with advanced stage disease at the time of diagnosis, it was recommended that screening MRI should be done in all patients presenting with hip complaints. Sir Salimullah Med Coll J 2022; 30: 180-185

Comparison of characteristics and outcomes of young onset versus average onset pancreatobiliary adenocarcinoma.

10522 Background: Young-onset gastrointestinal malignancies appear to be increasing in incidence but most investigations have focused on colorectal cancer and there are limited data on young-onset pancreatobiliary cancers (YO-PBA). We evaluated trends and characteristics of YO-PBA in comparison to average-onset disease (AO-PBA). Methods: The study cohort comprised patients with PBA (pancreatic adenocarcinoma, intra- and extra-hepatic cholangiocarcinoma) diagnosed between 2004 and 2017 from the National Cancer Database. YO-PBA was defined as diagnosis at age &lt; 50 years and AO-PBA as &gt;50 years. Logistic regression was used to assess factors associated with YO-PBA status, and cox proportional hazards modeling was performed to associate demographic and clinical factors with overall survival. Results: Of 360,764 patients analyzed, 20,822 (5.8%) were YO-PBA with a median age at diagnosis of 45 years (IQR 42 – 48) vs 70 (62-78) years for AO-PBA. The number of patients with YO-PBA increased by 33.3% during the study period compared to 111.8% for AO-PBA. Characteristics associated with YO-PBA were (p-values&lt;0.001 for all): male sex (6.3% YO-male out of all male patients vs 5.2% YO-female out of all female patients, OR 1.2), Black race (7.9% YO-Black vs 5.0% YO-White, OR 1.4), lower income (6.4% YO-lowest household income based category vs 5.5% highest, OR 1.3), and lower education (6.9% YO-lowest educational status category vs. 4.9% highest, OR 1.4). YO-PBA were more likely to present with stage-IV disease (6.4% YO-Stage IV of all stage IV vs 5.4% YO-Stage I-III, OR 1.2, p-value&lt;0.0001), but more likely to undergo surgery (7.4% YO-surgery patients vs 5.4% YO no-surgery patients). Median OS was YO 11.0 (95% CI 10.8 – 11.3) vs. AO 7.1 months (95% CI 7.0 – 7.1). Effects of patients’ characteristics on OS differed significantly between YO and AO-PBA cohorts (interaction p-values &lt; 0.001), and were analyzed separately (table). Notably, Black patients experienced worse outcomes in both age groups. Conclusions: Young-onset pancreatobiliary cancers (YO-PBA) reported in NCDB have increased over the years. YO-PBA is associated with better survival compared to AO-PBA. Socioeconomic disparities significantly impact incidence and outcomes. More work is needed to help address these health disparities, especially for those with young-onset cancer. [Table: see text]

Age and prognosis in patients with pancreatic cancer: a population-based study

Background The diagnosis of pancreatic ductal adenocarcinoma (PDAC) has an enormous impact on patients, and even more so if they are of younger age. It is unclear how their treatment and outcome compare to older patients. This study compares clinicopathological characteristics and overall survival (OS) of PDAC patients aged <60 years to older PDAC patients. Method This is a retrospective, population-based cohort study using Netherlands Cancer Registry data of patients diagnosed with PDAC (1 January 2015–31 December 2018). Kaplan–Meier curves and Cox proportional hazards models were used to assess OS. Results Overall, 10,298 patients were included, of whom 1551 (15%) were <60 years. Patients <60 years were more often male, had better performance status, less comorbidities and less stage I disease, and more often received anticancer treatment (67 vs. 33%, p < 0.001) than older patients. Patients <60 years underwent resection of the tumour more often (22 vs. 14%p < 0.001), more often received chemotherapy, and had a better median OS (6.9 vs. 3.3 months, p < 0.001) compared to older patients. No differences in median OS were demonstrated between both age groups of patients who underwent resection (19.7 vs. 19.4 months, p = 0.123), received chemotherapy alone (7.8 vs. 8.5 months, p = 0.191), or received no anticancer treatment (1.8 vs. 1.9 months, p = 0.600). Patients <60 years with stage-IV disease receiving chemotherapy had a somewhat better OS (7.5 vs. 6.3 months, p = 0.026). Conclusion Patients with PDAC <60 years more often underwent resection despite less stage I disease and had superior OS. Stratified for treatment, however, survival was largely similar.

Mismatch Repair Status Correlates with Survival in Young Adults with Metastatic Colorectal Cancer

BackgroundYoung adults with metastatic colorectal cancer (mCRC) may have higher rates of deficient mismatch repair (dMMR) than older patients. This study sought to assess patterns of MMR-testing and survival among young adult mCRC patients in the National Cancer Database (NCDB), hypothesizing that dMMR correlates with worse survival than in MMR-proficient (pMMR) patients. MethodsStage-IV colorectal cancers were identified in NCDB (2010-2016). Demographic and clinical features were compared between younger (age ≤ 30) and older mCRC patients and tested for association with overall survival. Stage-IV disease without other recorded metastatic sites defined peritoneal metastasis (PM). Fisher-exact tests compared proportions and Cox models tested association with overall survival. ResultsOf 124,587 stage-IV colorectal cancers, 1,123 (0.9%) were in young patients. Young patients were more likely to have mucinous histology, high-grade, rectal primaries, and isolated peritoneal metastases (P < 0.001). Younger patients more often had MMR-testing (29.1 versus 16.6%), with dMMR found at similar rates in young and older patients (21.7 versus 17.1% of those tested, P= 0.4). Despite higher rates of adverse prognostic features, younger patients had better survival (median 20.7 versus 14.8 months, P < 0.001). In MMR-tested patients, dMMR correlated with higher mortality risk compared to pMMR (median 16.6 months versus 25.5 months, P = 0.01). On multivariable analysis, grade and MMR-status remained independently associated with survival. ConclusionsMedian survival was worse with dMMR by 8.9 months compared to pMMR in young adults with mCRC. Despite higher rates of familial syndromes in young patients and recommendations for universal MMR-testing, over 70% of young mCRC patients had no MMR-status recorded.

Role of delayed interval debulking for persistent residual disease after more than 5 cycles of chemotherapy for primary advanced ovarian cancer. An international multicenter study

BackgroundStandard of care in patients with advanced ovarian cancer (AOC) is upfront surgery followed by chemotherapy. Neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS) is an alternative in selected patients. Most data exist with IDS following 3–4 cycles chemotherapy, however, some patients experience a delay of IDS. So far, the impact of a “delayed” interval debulking surgery (DID) is poorly defined. MethodsWe analyzed data from eight international gynecology-oncology referral centers. Patients were included if they had newly diagnosed AOC and were prone to DID (minimum 5 cycles of NACT) between 2011 and 2017. Results308 patients underwent DID. 89.6% had a high-grade serous ovarian cancer. The median number of pre-op NACT was 6 cycles (range 5–9) and 6.1% of patients received additionally bevacizumab. The majority of patients had stage-IV disease (51.3%). Median duration of surgery was 210 min (range 34–561), the median surgical complexity score was 4 (range 1–16). Complete resection was achieved in 60.1%. The median number of post-op chemotherapy cycles was 2 (range 0–5). The rate of severe complications (Clavien-Dindo£3°) was 9.7% and 30 days post-op mortality was 0.3%. The median PFS and OS in patients with complete resection was 19.5 and 49.2 months compared to 14.8 and 33.0 months in patients with incomplete resection (p = 0.001), respectively. We did not observe any survival benefit for patients with cytoreduction to small residuals (1–10 mm) compared to residual disease >1 cm. ConclusionOur data may suggest that offering surgery to patients with persistent disease after 5+ cycles could be associated with favorable outcome if a complete resection is achieved. Patients who had residual disease postoperatively may experience rather peri-operative treatment burden than any benefit from DID.

Real-world treatment patterns and survival in stage IV non-small-cell lung cancer in Canada.

Almost half of all patients with non-small-cell lung cancer (nsclc) present with stage iv disease. The objective of the present study was to characterize treatment patterns and survival outcomes in patients with advanced nsclc. We conducted a longitudinal population-level study in patients diagnosed with stage iv nsclc in Ontario between 1 April 2010 and 31 March 2015, with follow-up to 31 March 2017 for overall survival and treatment sequence. Patients were stratified as nonsquamous or squamous histology. A sub-analysis was conducted for patients with nonsquamous histology who received targeted therapies, on the assumption that their tumours were EGFR mutation-positive (EGFRm+). Treatment patterns were determined, and survival was calculated from date of diagnosis to death or censoring. Of 24,729 nsclc cases identified, stage iv disease was diagnosed in 49.2%, histology was nonsquamous in 10,103, and EGFRm+ was assumed in 508. Median patient age ranged from 69 to 72 years for the three cohorts. For patients with nonsquamous histology, palliative radiotherapy was the most frequently used first-line treatment (44.4%), followed by no treatment (26.7%) and chemotherapy (14.9%). In the EGFRm+ cohort, 75.6% received gefitinib as first- or second-line therapy, and almost half (47.4%) the 473 patients with squamous histology treated with first-line chemotherapy received cisplatin or carboplatin with gemcitabine. Median overall survival in the nonsquamous and squamous cohorts was 4.9 and 4.6 months respectively; it was 17.6 months for patients who were EGFRm+. Survival of patients with stage iv nsclc remains poor, with the exception of patients who are EGFRm+. Only 14.9% of patients received first-line chemotherapy; the mainstay of treatment was palliative radiotherapy.

Cholecystectomy for Resistant Metastatic Malignant Melanoma of the Gallbladder: A Case Report

Malignant melanoma is an unpredictable disease, known to metastasize early even in thin melanomas. Historically the presence of intraabdominal metastasis meant poor prognosis with a 5-year survival of less than 20%. That has significantly changed with effective systemic therapy (EST), with most recent studies reporting 5-year survival of up to 50%. Metastasecectomy for resistant disease has been considered in Stage IV disease, however there is very little literature on the combination of EST and metastasectomy. This report describes a case of Stage IV malignant melanoma patient who developed resistant disease within her gallbladder fundic wall. She underwent open cholecystectomy, with complete metabolic response at 1-year follow up PET.

Hypereosinophilia in a patient with refractory eczema and ALK-negative anaplastic large cell lymphoma

A 41-year-old man with refractory eczema on immunosuppressants developed swinging fever and dyspnoea, with left pleural effusion and left axillary and groin lymphadenopathy (2–3 cm) found in physical examination. Clinically there was no eczema flare-up. Laboratory tests showed hypereosinophilia (79.1×109/L) and elevated LDH (520 U/L) and ALP (187 U/L). Some dysplastic eosinophils showing hyposegmented nuclei and hypogranular cytoplasm were noted on blood smears. Workup for parasites, allergy and autoimmune markers was unremarkable. Thoracentesis yielded exudative effusate with numerous lymphocytes (WBC >1000/mm3) but no malignant cell was evident. FNAC of lymph nodes found eosinophilic infiltrate only. Bone marrow examination revealed marked eosinophilia with similar dysplastic features and megakaryocytic hyperplasia, raising suspicion of myeloproliferative neoplasms. Karyotyping, molecular tests for JAK2 mutation and BCR-ABL1 fusion, and FISH for FIP1L1-PDGFRA, PDGRFB and FGFR1 rearrangements were unremarkable. Excisional biopsy of left groin lymph node was then pursued and demonstrated sheets of pleomorphic neoplastic cells with focal ‘hallmark cells’. Anaplastic large cell lymphoma (ALK–CD30+CD3+CD8+) was diagnosed. PET/CT scan revealed a stage-IV disease with extensive supra- and infra-diaphragmatic hypermetabolic lymph nodes and multiple bone involvements. The patient opted for brentuximab vedotin plus combination chemotherapy. This case underscores the importance of exhaustive investigations and clinicopathological corroboration in the workup of hypereosinophilia.

The role of restaging MRI post neoadjuvant therapy for locoregionally advanced rectal cancer

Background: Rectal cancer management has evolved from surgery to neoadjuvant radiotherapy to total chemoradiotherapy regimens. Magnetic resonance imaging (MRI) is the gold standard for staging; however, its role for assessing response to neoadjuvant therapy is less than clear. Objective: To assess the role of restaging MRI post neoadjuvant long-course chemoradiotherapy (NA CRT) for locoregionally advanced rectal cancer. Design: A retrospective audit of prospectively collected data. Setting: A tertiary hospital colorectal unit. Patients and Methods: Patients with locoregionally advanced rectal adenocarcinoma (T3/T4 and/or nodal disease), who underwent restaging pelvic MRI scans post-NA CRT were included. Medical records of relevant radiology and operative histopathology were reviewed. Main Outcome Measures: To determine whether restaging MRI altered subsequent patient management (compared to the initial plan as documented in the pretreatment colorectal multidisciplinary team meeting). Sample Size: Twenty-three patients with restaging MRI. Results: On diagnosis, 15 patients (65.2%) had American Joint Committee on Cancer (AJCC) stage-III disease; two patients had AJCC stage-II disease (8.7%), and five patients (21.7%) had AJCC stage-IV disease with limited metastases (curative intent to treatment). Three patients had a complete clinical response (cCR) post NA CRT. Fourteen tumors had downstaging (MRI tumor regression grade 2-3, 58.3%). In three patients (13.0%), restaging MRI altered patient management. Two of them had extensive disease that underwent significant downstaging, enabling avoidance of a pelvic exenteration; and one also had sufficient downstaging and was able to have a sphincter preserving operation as a result. Conclusions: MRI may have a role in patients with the extensive locoregional disease or in ultralow rectal cancers where it is unclear if sphincter preservation is possible. Limitations: Small sample size; additionally, “watch and wait” methods are not routinely practiced in this tertiary unit. Conflict of Interest: None.

1776P - High incidence of venous thromboembolic events (VTE) in patients with diffuse large b-cell lymphoma

BackgroundIncidence of venous thromboembolic events (VTE) is higher among cancer patients, especially while on chemotherapy. Diffuse large B-cell lymphoma (DLBL) is the most common lymphoma. Studies that specifically evaluated the risk of VTE in patients with different kinds of lymphomas reported a risk ranged from 1.5% to 14.6%. In this study, we specifically address VTE in a unified lymphoma population. MethodsMedical records and hospital databases were searched for patients with a diagnosis of DLBL and VTE. All patients were diagnosed, treated and followed up at our institution. The Khorana and “Throly” risk assessment models (RAM) were applied on all patients and known risk factors for VTE were studied. ResultsA total of 393 patients (52.4% males), median age: 49 (range: 18-90) years were included. At diagnosis, 163 (41.5%) were stage IV, 116 (29.5%) had bulky disease and 197 (50.1%) had high LDH. All patients were treated on a unified guidelines using R-CHOP chemotherapy; 285 (72.5%) achieved CR while 72 (18.3) had salvage chemotherapy. Venous thromboembolic events were reported in 57 (14.5%) patients. Pulmonary embolism (PE) with or without deep venous thrombosis (DVT) was reported in 24 (42.1%), 8 of them (33.3%) were incidental. Upper extremity DVT were seen in 18 (31.6%); only 4 (22.2%) were associated with a vascular device. Thrombosis was diagnosed in ambulatory sitting in 30 (52.6%) and majority of the VTE occurred while on active chemotherapy; 20 (35.1%) while on initial induction and 15 (26.3%) while on salvage chemotherapy, however, 19 (33.3%) occurred before the initiation of any chemotherapy. Among the 35 patients on active chemotherapy, only 6 (17.1%) had high Khorana risk score. In a multivariate analysis, significantly higher rates of thrombosis were associated with stage-IV disease, high LDH and high International Prognostic Index (IPI). Sex, age, BMI, and the Khorana risk score were not. ConclusionsIncidence of VTE in patients with DLBL is high and majority of such events occurred in ambulatory setting were VTE prophylaxis is not offered. Upper extremity DVT and incidental PE were exceptionally high. Stage at diagnosis, IPI score and LDH are important in predicting the risk for thrombosis. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.