Publications by authors named "Konda B"

Hypoxia-induced radioresistance limits therapeutic success in cancer. In addition, p53 mutations are widespread in tumors including non-small cell lung carcinomas (NSCLCs), and they might modify the radiation response of hypoxic tumor cells. We therefore analyzed the DNA damage and inflammatory response in chronically hypoxic (1% O, 48 h) p53 null H358 NSCLC cells after X-ray exposure.

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BACKGROUNDInhibition of Bruton's tyrosine kinase with ibrutinib blocks the function of myeloid-derived suppressor cells (MDSC). The combination of ibrutinib and nivolumab was tested in patients with metastatic solid tumors.METHODSSixteen patients received ibrutinib 420 mg p.

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Background: Treatment options for patients with advanced neuroendocrine tumors are limited. The efficacy of cabozantinib in the treatment of previously treated, progressive extrapancreatic or pancreatic neuroendocrine tumors is unclear.

Methods: We enrolled two independent cohorts of patients - those with extrapancreatic neuroendocrine tumors and those with pancreatic neuroendocrine tumors - who had received peptide receptor radionuclide therapy or targeted therapy or both.

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Introduction: Locoregional therapies are a mainstay of treatment for patients with neuroendocrine liver metastases (NELM), yet the optimal transarterial approach remains undefined and recent studies have raised concern over the safety of transarterial chemoembolization (TACE).

Methods: Patients with NELM who underwent TACE or transarterial embolization (TAE) at a single institution between 2000-2022 were retrospectively reviewed. Propensity score matching (PSM) controlling for age, sex, bilateral disease, tumor size, lobar embolization, grade, and extrahepatic disease was utilized to compare short- and long-term outcomes.

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Article Synopsis
  • This phase II trial investigated the effectiveness of cabozantinib combined with nivolumab and ipilimumab (CaboNivoIpi) in patients with radioactive iodine-refractory differentiated thyroid cancer who had previously received treatment.
  • The study involved 11 patients, with a median age of 69, and showed an objective response rate of only 10% after 6 months, along with a median progression-free survival of 9 months and overall survival of 19.2 months.
  • Despite some signs of activity, the trial encountered a significant rate of severe adverse events (55% grade 3/4 and 18% grade 5), and did not meet its predefined efficacy goals.
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Article Synopsis
  • Lenvatinib, a multikinase inhibitor, is effective in improving progression-free survival (PFS) in patients with radioiodine-refractory differentiated thyroid cancer, leading to a study on its combination with pembrolizumab.
  • The study enrolled two groups: naïve patients to multikinase inhibitors and those who progressed on lenvatinib, with results showing a 65.5% overall response rate in naïve patients but only 16% in those who previously had lenvatinib.
  • Findings suggest that the combination therapy may improve treatment durability for naïve patients and could serve as a potential salvage option for those whose cancer progressed on lenvatinib alone.
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Peptide receptor radionucleotide therapy (PRRT) with 177Lu-dotatate is widely used for the treatment of patients with neuroendocrine tumors (NETs). We analyzed data from 104 patients with NETs treated with 177Lu -dotatate at a US academic center between December 2017 and October 2020 to better understand patterns of long-term efficacy, safety, and toxicity in the real-world setting. 177Lu-dotatate (200 mCi) was administered every eight weeks for four doses.

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Cellular hypoxia, detectable in up to 80% of non-small cell lung carcinoma (NSCLC) tumors, is a known cause of radioresistance. High linear energy transfer (LET) particle radiation might be effective in the treatment of hypoxic solid tumors, including NSCLC. Cellular hypoxia can activate nuclear factor κB (NF-κB), which can modulate radioresistance by influencing cancer cell survival.

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Article Synopsis
  • Activating RET alterations have been found in various solid tumors, including pheochromocytoma, which can occur sporadically or in familial cases linked to MEN2 syndromes.
  • Selpercatinib, a potent RET kinase inhibitor, showed significant anti-tumor effects in the LIBRETTO-001 study, specifically in six pheochromocytoma patients treated with it.
  • Out of these patients, four experienced a partial or complete response while two had stable disease, indicating that selpercatinib is a promising therapy for RET-mutant pheochromocytoma.
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Hypoxia-induced radioresistance reduces the efficacy of radiotherapy for solid malignancies, including non-small cell lung cancer (NSCLC). Cellular hypoxia can confer radioresistance through cellular and tumor micro-environment adaptations. Until recently, studies evaluating radioresistance secondary to hypoxia were designed to maintain cellular hypoxia only before and during irradiation, while any handling of post-irradiated cells was carried out in standard oxic conditions due to the unavailability of hypoxia workstations.

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Objectives: To describe the first reported use of neoadjuvant dabrafenib and trametinib specifically to permit organ conservation surgery in locally advanced recurrent differentiated thyroid carcinoma.

Patients And Methods: A patient presented with locally recurrent, radioiodide-resistant DTC with a BRAF V600E mutation invading the laryngotrachea. Definitive treatment would require a total laryngectomy.

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Article Synopsis
  • - A subset of patients with differentiated thyroid carcinoma experiences radioiodine refractory disease, which has a poor prognosis, but treatment with the drug lenvatinib has shown benefits in progression-free survival for these cases.
  • - In the SELECT trial for lenvatinib, 5.4% of patients reported arterial thromboembolic events, and 2.7% experienced severe toxicities related to vascular complications.
  • - A case study highlighted a patient with metastatic thyroid cancer who developed serious coronary artery disease after starting lenvatinib, underscoring the need to assess cardiovascular risk before treatment, even if patients lack traditional risk factors.
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Introduction: The rearranged during transfection (RET) mutation is an oncogene driver for the development of cancer. Selpercatinib is a highly selective RET inhibitor that has demonstrated anti-tumor activity in RET-mutated cancers. Selpercatinib is approved for use in RET fusion-positive non-small-cell lung cancer (NSCLC), RET-mutated medullary thyroid cancer, RET fusion-positive thyroid cancer, and RET fusion-positive solid tumors.

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Objective: The treatment landscape for thyroid cancers has changed rapidly with the availability of kinase inhibitors against VEGFR, BRAF, MEK, NTRK, and RET. We provide an up-to-date review of the role of kinase inhibitors in thyroid cancer and discuss upcoming trials.

Design & Methods: A comprehensive review of the available literature describing kinase inhibitors in thyroid cancer was performed.

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Hypoxia occurs in 80% of non-small cell lung carcinoma (NSCLC) cases, leading to treatment resistance. Hypoxia's effects on NSCLC energetics are not well-characterized. We evaluated changes in glucose uptake and lactate production in two NSCLC cell lines under hypoxia in conjunction with growth rate and cell cycle phase distribution.

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Rationale And Objectives: To evaluate single-institution outcomes of drug-eluting bead transarterial chemoembolization (DEB-TACE) in the treatment of locally advanced neuroendocrine tumor (NET) hepatic metastases with a focus on safety and efficacy of treatment.

Materials And Methods: A single-center retrospective cohort study of the outcomes of consecutive patients with NELM who underwent DEB-TACE between 2014 and 2019 was performed. Clinicopathologic characteristics, radiologic response (modified Response Evaluation Criteria in Solid Tumors) at 1-month follow-up, adverse events, progression-free survival (PFS), and overall survival were calculated.

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Introduction: Exposure to space conditions during crewed long-term exploration missions can cause several health risks for astronauts. Space radiation, isolation and microgravity are major limiting factors. The role of astrocytes in cognitive disturbances by space radiation is unknown.

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Background: In the phase 2 double-blind Study 211, a starting dose of lenvatinib 18 mg/day was compared with the approved starting dose of 24 mg/day in patients with radioiodine-refractory differentiated thyroid cancer (RR-DTC). Predefined criteria for noninferiority for efficacy in the 18 mg arm were not met; safety was similar in both arms. Impact of lenvatinib treatment on health-related quality-of-life (HRQoL) was a secondary endpoint of Study 211.

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Dysfunction of alveolar epithelial type 2 cells (AEC2s), the facultative progenitors of lung alveoli, is implicated in pulmonary disease pathogenesis, highlighting the importance of human in vitro models. However, AEC2-like cells in culture have yet to be directly compared to their in vivo counterparts at single-cell resolution. Here, we performed head-to-head comparisons among the transcriptomes of primary (1°) adult human AEC2s, their cultured progeny, and human induced pluripotent stem cell-derived AEC2s (iAEC2s).

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Purpose: Treatment options are limited in patients with metastatic neuroendocrine neoplasms (NEN). We present the results for a phase II trial of combination nivolumab and temozolomide in patients with advanced NEN along with results of immune changes in peripheral blood.

Patients And Methods: NCT03728361 is a nonrandomized, phase II study of nivolumab and temozolomide in patients with NEN.

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