Treatment Outcomes and Relative Dose Intensity of Chemotherapy in Slovene Patients With Advanced Hodgkin Lymphoma

This retrospective study was undertaken to investigate the association of relative dose intensity (RDI) with the outcome of Hodgkin lymphoma (HL) patients with advanced stage disease receiving ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) and escalated BEACOPP regimen (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone). A total of 114 HL patients treated between 2004 and 2013 were enrolled for evaluation. RDI calculations were based on a Hryniuk's model. The association of variables with overall survival (OS) and progression-free survival (PFS) was analysed using univariate and multivariate Cox proportional hazards models. The median age of patients was 39 years, majority of patients were males and had stage IV disease. Fifty-four patients received ABVD and 60 received BEACOPP chemotherapy with 24 and 4 deaths, respectively. Patients in BEACOPP group were significantly younger with lower Charlson comorbidity index (CCI) in comparison with ABVD group, making the comparison of groups impossible. In ABVD group, RDI was not significantly associated with OS (p=0.590) or PFS (p=0.354) in a multivariate model where age was controlled. The low number of events prevented the analysis in the BEACOPP group. Patients' age was strongly associated with both OS and PFS: all statistically significant predictors for OS and PFS from univariate analyses (chemotherapy regimen, CCI, RDI) lost its effect in multivariate analyses where age was controlled. Based on our observations, we can conclude that RDI is not associated with the OS or PFS after the age is controlled, neither in all patients combined nor in individual chemotherapy groups.

Initial treatment and survival in Danish patients diagnosed with non-small-cell lung cancer (2005–2015): SCAN-LEAF study

Aim: To describe initial treatment patterns and survival of patients diagnosed with non-small-cell lung cancer (NSCLC) in Denmark, before immune checkpoint inhibitor and later-generation tyrosine kinase inhibitor use. Patients & methods: Adults diagnosed with incident NSCLC (2005–2015; follow-up: 2016). Initial treatments and overall survival (OS) are reported. Results: 31,939 NSCLC patients (51.6% stage IV) were included. Increasing use of curative radiotherapy/chemoradiation for stage I, II/IIIA and IIIB NSCLC coincided with improved 2-year OS. Systemic anticancer therapy use increased for patients with stage IV non-squamous NSCLC (53.0–60.6%) but not squamous NSCLC (44.9–47.3%). 1-year OS improved in patients with stage IV non-squamous NSCLC (23–31%) but not squamous NSCLC (22–25%). Conclusion: Trends indicated improved OS as treatments evolved between 2005 and 2015, but the effect was limited to 1-year OS in stage IV disease.

Different Therapeutic Strategies in 2 Young Patients with Advanced ALK-Rearranged Lung Adenocarcinoma: “The Light at the End of the Tunnel”

Malignant pleural effusion represents a prognostic negative factor on survival conferring stage IV disease. The median of survival is 5 months and a 5-year survival of about 3%. We describe the therapeutic success obtained from different strategies in anaplastic lymphoma kinase (ALK) inhibitors in 2 young women showing malignant pleural effusion secondary to advanced ALK-rearranged lung adenocarcinoma. This report shows that for patients with EGFR mutations in advanced lung adenocarcinoma-associated malignant pleural effusion, complete response to EGFR TKI inhibitor can be observed mostly if pleural effusion and primary lung adenocarcinoma show the same EGFR mutation status.

Birtamimab in Patients with Mayo Stage IV AL Amyloidosis: Rationale for Confirmatory Affirm-AL Phase 3 Study Design

Background: Light chain (AL) amyloidosis is a rare, progressive, and typically fatal hematologic disorder caused by plasma cells that produce misfolded AL protein, resulting in deposits of amyloid in tissues and organs that cause organ dysfunction and failure. Birtamimab is an investigational monoclonal antibody designed to neutralize circulating soluble amyloid and deposited insoluble amyloid, thus promoting the phagocytic clearance of amyloid deposits. In 2018, the global phase 3 VITAL study in newly diagnosed, treatment-naïve patients was terminated based on a futility analysis of the composite primary endpoint (time to all-cause mortality [ACM] or time to cardiac hospitalization >90 days after first study drug infusion); the final hazard ratio (HR) numerically favored birtamimab + standard of care (SOC) over placebo + SOC (0.835, 95% CI 0.5799, 1.2011; p=0.330). Post hoc analysis of ACM over 9 months revealed a pronounced survival benefit (HR=0.413, 95% CI 0.191, 0.895; p=0.025; Figure) in a subgroup of patients at high risk for early mortality (Mayo stage IV). At 9 months, the proportions of surviving patients were 74% and 49% in the birtamimab + SOC and placebo + SOC groups, respectively. Post hoc analyses of secondary endpoints in this subgroup also supported clinical and functional benefits of birtamimab + SOC, with clinically meaningful improvements observed in health-related quality of life (assessed with 36-Item Short Form Health Survey version 2; SF-36v2) and 6-minute walk test (6MWT) distance (both nominal p<0.05) at 9 months. Across all birtamimab clinical trials, no drug-related deaths, dose-limiting toxicities, or major risks were identified. Aims: To evaluate the efficacy and safety of birtamimab + SOC versus placebo + SOC in Mayo stage IV patients with AL amyloidosis by assessing time to ACM over 9 months. Methods: The phase 3, double-blind, placebo-controlled AFFIRM-AL study will enroll up to 150 Mayo stage IV patients with newly diagnosed, untreated AL amyloidosis. Patients will receive either 24 mg/kg intravenous birtamimab or placebo every 28 days (both arms will also receive SOC, defined as concomitant chemotherapy with a first-line bortezomib-containing regimen). Patients will be randomly assigned 2:1 to birtamimab or placebo and will be stratified at randomization based on their 6MWT distance (<300 meters vs ≥300 meters). The primary efficacy endpoint of AFFIRM-AL is time to ACM using a log-rank test. Secondary endpoints are change from baseline to month 9 in SF-36v2 and 6MWT distance. Safety endpoints include adverse events, clinical laboratory observations, and immunogenicity analyses. An interim efficacy analysis is planned when ~50% of the events have occurred. Results: Given the >50% relative risk reduction for ACM observed in the post hoc analysis of VITAL for the AL amyloidosis subpopulation of patients with Mayo stage IV disease, the phase 3 AFFIRM-AL study is designed to confirm this effect of birtamimab under a Special Protocol Assessment agreement with the US FDA. Conclusion/Summary: Effective treatments to improve survival in AL amyloidosis are needed, particularly for patients with advanced cardiac involvement, as median overall survival for those with Mayo stage IV disease is approximately 6-9 months. Birtamimab is the only investigational therapeutic in which a survival benefit has been observed, in a post hoc subgroup analysis of VITAL in patients with AL amyloidosis with advanced cardiac involvement. AFFIRM-AL is expected to initiate in mid-2021. (NCT04973137) Figure 1 Figure 1. Disclosures Gertz: Alnylam, Amgen, Annexon, Appellis, Celgene, Ionis/Akcea, Janssen, Medscape, Physicians Education Resource, Prothena, Research to Practice: Other: personal fees; Spectrum: Other: personal fees, Research Funding; AbbVie: Other: personal fees for Data Safety Monitoring board; Teva, Johnson and Johnson, Medscape, DAVA oncology: Other: speaker fees; Pharmacyclics, Proclara: Other: Advisory Board; i3Health: Other: development of educational materials; Springer Publishing: Patents & Royalties. Tripuraneni: Prothena Biosciences Inc.: Current Employment, Current holder of stock options in a privately-held company, Patents & Royalties: related to birtamimab (NEOD001). Kinney: Prothena Biosciences Inc.: Current Employment, Current holder of stock options in a privately-held company, Patents & Royalties: related to birtamimab (NEOD001).

Nationwide evaluation of mutation-tailored anti-EGFR therapy selection in patients with colorectal cancer in daily clinical practice

For a nationwide real-word data study on the application of predictive mutation testing of patients with colorectal cancer (CRC) for anti-epidermal growth factor receptor (EGFR) therapy stratification, pathology data were collected from the Dutch Pathology Registry from October 2017 until June 2019 (N=4060) and linked with the Netherlands Cancer Registry. Mutation testing rates increased from 24% at diagnosis of stage IV disease to 60% after 20–23 months of follow-up (p<0.001). Application of anti-EGFR therapy in KRAS/NRAS wild-type patients was mainly observed from the third treatment line onwards (65% vs 17% in first/second treatment line (p<0.001)). The national average KRAS/NRAS/BRAF mutation rate was 63.9%, being similar for next-generation sequencing (NGS)-based approaches and single gene tests (64.4% vs 61.2%, p=ns). NGS-based approaches detected more additional potential biomarkers, for example, ERBB2 amplifications (p<0.05). Therefore, single gene tests are suitable to stratify patients with mCRC for anti-EGFR therapy, but NGS is superior enabling upfront identification of therapy resistance or facilitate enrolment into clinical trials.

Crizotinib in Sarcomatous Malignancies Harboring ALK Fusion With a Definitive Partner(s): Response and Efficacy

Sarcoma or sarcomatoid malignancies are a set of mesenchymal-origin malignancies with vast heterogeneity in clinical and molecular characteristics. Anaplastic lymphoma kinase (ALK) is a tyrosine kinase oncoprotein expressed by several tumors, including sarcomas. Crizotinib is an effective ALK inhibitor. In this review paper, we summarized findings from the literature regarding the use of crizotinib for the treatment of sarcoma and sarcomatoid malignancies harboring ALK fusions with definitive partners (with the given gene(s) name) from the years 2010 to 2021.One hundred and four articles were retrieved and after exclusion, 28 studies containing 33 patients were finally selected. All 33 patients were treated with crizotinib. Among the 33 cases, 19 were adult patients, 11 were pediatric patients, and 3 cases did not have data on age and/or gender. Most cases had a primary abdominal lesion (16/30), followed by thoracic (10/30), trunk (3/30), retroperitoneal (1/30), and one case of right medial thigh (case 7). Stage IV disease was reported in 76.7% (23/30) of patients. The objective response rate and disease control rate was 86.7% (26/30) and 96.7% (29/30), respectively, which were assessed on average of 8 weeks after crizotinib initiation. Rapid improvement of symptoms was observed within one to two weeks in some cases including patients with extensive diseases or poor performance. There was no difference in crizotinib response between pediatrics and adult cases. Crizotinib is effective; however, surgery remains the mainstay of therapy, with newer evidence showing concurrent crizotinib with surgery conferring long-term overall survival. However, we should still be cognizant of the heterogeneous landscape of crizotinib efficacy and its associated fatal adverse events.

Patidegib in Dermatology: A Current Review

Background: Basal cell carcinoma is one of the most common types of non-melanoma skin cancers, which can be locally destructive despite low-rate metastasis. Surgery is the treatment of choice, but it lacks of efficacy on advanced cases. Hedgehog pathway inhibitors are a class of drugs providing a new therapeutic option for patients affected by advanced disease. Besides systemic therapy, such as vismodegib and sonidegib, also topical inhibitors have been developed. Patidegib is able to decrease tumor burden, reducing the adverse effects induced by systemic targeted therapies. Methods: We performed comprehensive research to summarize the use of patidegib in advanced and recurrent aggressive basal cell carcinomas. Only English language human studies were included in the search. Results: Seven trials reported the application of patidegib. Both topical and systemic patidegib demonstrated safety, tolerability, and efficacy in naïve patients with stage II and III basal cell carcinomas, while stage IV disease and not-naïve patients did not show any benefit. Conclusion: Unlike systemic Hedgehog pathway inhibitors, patidegib 2% gel is not associated with systemic adverse effects and allows a better patient management. Considering the multidisciplinary management of neoplasia, in the era of precision medicine, it is mandatory to confide in pharmacogenomics to obtain personalized combined or sequential therapies.

The effect of quality improvement interventions on inpatient cancer malnutrition documentation and coding in an academic medical center.

38 Background: Malnutrition (MN) is common yet underdiagnosed in hospitalized cancer patients. Effective assessments can identify those who need nutritional care and help plan intervention. We examined the effect of quality improvement (QI) interventions on the dietitian documented MN (DDMN) and physician coded malnutrition (PCMN). We also determined if the registered dietitian (RD) and physician assessments of MN agreed. Methods: Electronic medical records (EMR) were reviewed for a consecutive cohort of inpatients with a solid tumor diagnosis staged I-IV and admitted to Atrium Health’s Carolinas Medical Center at least once between 1/1/2016 to 5/31/2019. Data were collected from the first admission EMR encounter closest to the cancer diagnosis date. RD assessments were reviewed for DDMN. PCMN diagnosis was based on MN ICD-10 codes in the discharge summary. MN was graded as mild, moderate, and severe. Two QI interventions were implemented during the study period: 1) 8/2016: RD message via EMR to query MD approval for MN diagnosis; 2) 4/2018: Clinical Documentation Integrity Team query MD by sending ASPEN criteria via an alert integrated into MD workflow. Agreement in MN identification was defined as the absence or presence of both DDMN and PCMN; agreement in severity was defined as the absence of DDMN and PCMN or the agreement in presence and severity of DDMN and PCMN. Cochran-Armitage tests for trend assessed prevalence and agreement across the three periods (N1=652; N2=2858; N3=1622) defined by the two sequential QI interventions. Results: N=5143; 52% males. Median age 63 (range 18-102) years. 70% White; 24% Black, 3% Latino. Commonest cancer diagnostic groups: Upper Gastrointestinal 22%, Thoracic (19%), Genitourinary 18%. 28% had stage IV disease. 11% (N=557) met criteria for DDMN and/or PCMN. Of the 557, 40% (N=223) met criteria for both DDMN and PCMN. DDMN (N=420) was mild 2%, moderate 19%, and severe 79%. On discharge, PCMN (N=360) was mild in 10%, moderate in 21%, and severe in 69%. The RD and MD agreed on the presence or absence (94%) and severity (93%) of MN. Significant trends were observed as DDMN prevalence increased from 3.1%, 8.1%, to 10.3% (p<.001), and PCMN prevalence from 0.5%, 7.8%, to 8.2% (p<.001). While rates of mild, moderate, and severe MN varied across the periods, statistically significant change in these distributions was not identified in DDMN (p=0.62) or PCMN (p=0.20) after the second QI intervention. Conclusions: MN was under-diagnosed compared to nutrition intervention studies. When MN was identified, it was moderate or severe in the majority. Evaluations by RD and MD were highly congruent for MN prevalence and severity. Implementation of nutrition-focused QI interventions improved documentation and coding of MN. Improved communication between the RD and the MD could improve the recognition and diagnosis of MN.

Evaluation of an oncology diagnostic and screening clinic at a large safety net hospital.

94 Background: Increasingly, dedicated clinics have been established to expedite patients with suspicion of malignancy into cancer care. The Lyndon B. Johnson General Hospital (LBJGH) is part of the Harris County Hospital District (HCHD), serving the third largest county in the United States. A 2012 study at our institution found long mean ambulatory wait times for the diagnosis of breast, colon, and lung cancers (77.1 days, 65.4 days, and 70.8 days, respectively). The LBJGH Oncology Diagnostic and Screening clinic (DSC) was subsequently established to reduce ambulatory diagnostic times, decrease frequency of admissions, and improve patient outcomes. Our present study sought to establish the effectiveness of the DSC in bringing patients into care. Methods: The charts of 100 new patients seen in the DSC between August 2018 and November 2020 were reviewed. Demographic data, insurance status, date of referral to the DSC, date of first DSC visit, date biopsy or outside pathology ordered, date biopsy performed or outside pathology obtained, total number of visits to the DSC, and total time from initial DSC visit to initial oncology clinic visit were collected, as well as cancer stage upon arrival to the oncology clinic. The project was approved by the MD Anderson Quality Improvement Assessment Board and the Harris Health Quality Improvement Committee. Results: 57% of patients seen in the DSC were referred by the emergency department, and 23% by a PCP. The median time from referral to initial visit in the DSC was 19 days. 26% of patients had a known cancer diagnosis at the time of referral. The median time from biopsy ordered to performed was 39 days, and the median time from pathology requested to obtained was 23 days. The median total number of visits per patient to the DSC was 2. 48% of patients seen in the DSC were ultimately diagnosed with cancer, 29% had a benign condition, and 23% were lost to follow up. Of those patients with confirmed malignancy, 46% of patients had stage IV disease at their first oncology clinic visit. The average time from initial DSC visit to initial visit at the oncology clinic was 53 days. Conclusions: Establishment of an oncology DSC has improved the ambulatory wait time for entry into oncologic care from an average of approximately 70 days to an average of 53 days. However, almost half of patients referred from the DSC had stage IV disease at their initial oncology visit, indicating an urgent need to further expedite entry of these patients into oncologic care. Avenues for future quality improvement efforts include an expedited process to obtain outside pathology results, implementation of an “e-consult” option for PCPs to avoid unnecessary referrals, and a close analysis of insurance and financial barriers to entry into care. Reference: Mougalian SS, Wang J, Zarzour M et al. Feasibility and savings of a suspicion of cancer clinic at a large county hospital. JCO 2012; 30 (34 supplement): 104.

Clinicopathological and Prognostic Features of 67 Cases with Pulmonary Sarcomatoid Carcinoma: An 18-Year Single-Centre Experience

<b><i>Introduction:</i></b> Pulmonary sarcomatoid carcinoma (PSC) is a very rare subtype of non-small-cell lung cancer (NSCLC). It is frequently diagnosed in the advanced stage and is resistant to conventional chemotherapeutics. Due to the unique nature and rarity, we evaluated the epidemiological, clinicopathological, and survival data of PSC patients treated at our centre. <b><i>Patients and Methods:</i></b> We retrospectively collected demographic and clinical data of 67 PSC patients from a single tertiary referral hospital, between the 2000 and 2018. Univariate and multivariate analyses were performed to determine the risk factors affecting survival. <b><i>Results:</i></b> The median age was 61 years, and the percentage of male was 74.6%. Most of the patients had a smoking history (76.9%). The most common PSC subtype was pleomorphic carcinoma (46.3%). The median overall survival (OS) was 55.4 months, and the 5-year OS rate was 47.5%. Advanced stage, T4 tumour, and positive lymph node involvement were associated with poor OS (<i>p</i> &#x3c; 0.05). The patients with negative epithelial markers had poorer prognosis (<i>p</i> = 0.027) and had more frequently stage IV disease (<i>p</i> = 0.016). Surgical treatment and stage IV disease were determined to be independent prognostic factors. <b><i>Conclusion:</i></b> PSC is an extremely rare and aggressive variant of NSCLC. Positive epithelial markers may have favourable prognostic significance in PSC. Resection of the tumour with a negative surgical margin is crucial for better survival. The prognosis of the disease is very poor in the metastatic stage.