Background Anal squamous cell carcinoma (SCCA) is an uncommon malignancy with a rising incidence that has a high cure rate in its early stages. There is an unmet need for a reliable method to monitor response to treatment and assist in surveillance. Circulating tumor DNA (ctDNA) testing has shown great promise in other solid tumors for monitoring disease progression and detecting relapse in real time. This study aimed to determine the feasibility and use of personalized and tumor-informed ctDNA testing in SCCA. Patients and Methods We analyzed real-world data from 251 patients (817 plasma samples) with stages I-IV SCCA, collected between 11/5/19 and 5/31/22. The tumor genomic landscape and feasibility of ctDNA testing was examined for all patients. The prognostic value of longitudinal ctDNA testing was assessed in patients with clinical follow-up (N = 37). Results Whole-exome sequencing analysis revealed PIK3CA as the most commonly mutated gene, and no associations between mutations and stage. Anytime ctDNA positivity and higher ctDNA levels (MTM/mL) were associated with metastatic disease (P = .004). For 37 patients with clinical follow-up, median follow-up time was 21.0 months (range: 4.1-67.3) post-diagnosis. For patients with stages I-III disease, anytime ctDNA-positivity after definitive treatment was associated with reduced DFS (HR: 28.0; P = .005). Conclusions Our study demonstrates the feasibility of personalized and tumor-informed ctDNA testing as an adjunctive tool in patients with SCCA as well as potential use for detection of molecular/minuteimal residual disease, and relapse during surveillance. Prospective studies are needed to better evaluate the use of ctDNA testing in this indication.
Cough is one of the most common symptoms prompting patients to be seen by health care providers in the United States. Persistent cough can disrupt daily activities such as conversation, eating, breathing, and sleeping, and it can become extremely debilitating both physically and mentally. Pharmacological treatments include dextramethorphan, opioid cough suppressants, benzonatate, inhaled ipratropium, and guaifenesin. Successful cough suppression has also been demonstrated in several studies with the use of nebulized lidocaine. Nebulized lidocaine also appears to be well tolerated by patients with minimal side effects including dysphonia, oropharyngeal numbness, and bitter taste. Studies conducted thus far have been small, so larger randomized control trials comparing nebulized lidocaine to placebo need to be conducted in the future.
PURPOSE Circulating tumor DNA (ctDNA) analyses allow for postoperative risk stratification in patients with curatively treated colon and breast cancers. Use of ctDNA in esophagogastric cancers (EGC) is less characterized and could identify high-risk patients who have been treated with curative intent. METHODS In this retrospective analysis of real-world data, ctDNA levels were analyzed in the preoperative, postoperative, and surveillance settings in patients with EGC using a personalized multiplex polymerase chain reaction–based next-generation sequencing assay. Plasma samples (n = 943) from 295 patients at > 70 institutions were collected before surgery, postoperatively, and/or serially during routine clinical follow-up from September 19, 2019, to February 21, 2022. ctDNA detection was annotated to clinicopathologic features and recurrence-free survival. RESULTS A total of 295 patients with EGC were analyzed, and 212 patients with stages I-III disease were further explored. Pretreatment ctDNA was detected in 96% (23/24) of patients with preoperative time points. Postoperative ctDNA was detected in 23.5% (16/68) of patients with stage I-III EGC within 16 weeks (molecular residual disease window) after surgery without receiving systemic therapy. ctDNA detection at any time point after surgery (hazard ratio [HR], 23.6; 95% CI, 10.2 to 66.0; P < .0001), within the molecular residual disease window (HR, 10.7; 95% CI, 4.3 to 29.3; P < .0001), and during the surveillance period (HR, 17.7; 95% CI, 7.3 to 50.7; P < .0001) was associated with shorter recurrence-free survival. In multivariable analysis, ctDNA status and clinical stage of disease were independently associated with outcomes. CONCLUSION Using real-world data, we demonstrate that postoperative tumor-informed ctDNA detection in EGC is feasible and allows for enhanced patient risk stratification and prognostication during curative-intent therapy.
TPS3155 Background: Anaplastic lymphoma kinase ( ALK) fusions are found in 3–8% of non-small cell lung cancers (NSCLC) and ̃0.2% of other tumor types. Alectinib is a selective, CNS-active ALK tyrosine kinase inhibitor approved as first-line treatment for adults with advanced ALK fusion-positive ( ALK-fp) NSCLC based on the phase 3 ALEX trial (NCT02075840; PMID 28586279). Preliminary evidence supports investigation of alectinib in a tumor-agnostic setting. ALK inhibitors have shown efficacy in ALK-fp tumor types other than NSCLC (PMIDs 29685646; 28977547; 30591488), with alectinib showing efficacy irrespective of ALK fusion partner and against ALK-activating mutations (PMIDs 29642598; 29559559). Methods: Alpha-T is a phase 2 open-label, single-arm trial (NCT04644315) with an innovative home-based remote design, currently enrolling adults with histologically confirmed, locally advanced/metastatic solid tumors (except lung cancer and cancers of unknown primary) harboring ALK fusions or selected mutations ( ALK-mut; R1275Q, F1245C, F1174X). The decentralized design permits enrollment regardless of location, allows most assessments to be home-based and maintains the relationship between patients (pts) and their treating oncologist. Key inclusion criteria: no alternative or unsuitable to receive standard therapy; ECOG PS 0–2; adequate hematologic, renal and hepatic functions; no prior ALK inhibitor; measurable solid tumor (RECIST 1.1) or primary brain tumor (RANO); asymptomatic or stable CNS metastases permitted. Pts are identified via the Foundation Medicine Inc. (FMI) Precision Enrollment service. For any solid tumor identified as ALK+ (fusion/selected mutation) by next-generation sequencing in tissue/blood (F1 CDx/F1L CDx, FMI), the ordering oncologist is given trial details and can liaise with a Science 37 investigator. Pts receive 600mg oral alectinib twice a day with food until radiological PD, unacceptable toxicity, withdrawal of consent or death. Home-based assessments (eg, physical examination, blood sampling, questionnaire completion) are conducted in-person by a mobile nurse at baseline and every 4 weeks, with remote support from the Science 37 investigator via their telemedicine platform. Tumor assessments at screening and every 8 weeks are performed at a local radiology facility. Primary endpoint: confirmed ORR by investigator in pts with ALK-fp tumors (RECIST 1.1). Secondary endpoints: ORR by independent review facility (IRF); DoR and PFS; intracranial ORR and DoR (IRF); OS and safety. Descriptive analyses are planned for pts with ALK-mut tumors and primary brain tumors. Pharmacokinetics and biomarkers will be evaluated. Patient-reported outcomes will be assessed via the EORTC QLQ-C30 and EuroQoL EQ-5D-5L questionnaires. Target enrollment is 50 pts with ALK-fp tumors evaluable by RECIST. As of 9 Feb 2021, 1 pt is in screening. Clinical trial information: NCT04644315.
The simultaneous occurrence of two different neoplasms is uncommon, and collision tumors are even rarer. We describe a cutaneous collision tumor of melanoma and mantle cell lymphoma presenting synchronously in a previously healthy individual. KEYWORDS Collision; lymphoma; melanoma C ollision tumors denote the rare occurrence of two or more tumors that are histologically different at the same anatomical site. They can occur due to two different tumors arising from the same organ or due to metastasis from a different site. 1 The association between cutaneous melanoma and non-Hodgkin's lymphoma (NHL) has been previously reported. 2 We describe a cutaneous collision tumor of melanoma and mantle cell lymphoma (MCL) presenting synchronously in a previously healthy patient.
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