-
The Oncologist Jun 2024A patient with gastrointestinal stroma tumor (GIST) and KIT p.V559D and BRAF p.G469A alterations was referred to our institutional molecular tumor board (MTB) to discuss...
A patient with gastrointestinal stroma tumor (GIST) and KIT p.V559D and BRAF p.G469A alterations was referred to our institutional molecular tumor board (MTB) to discuss therapeutic implications. The patient had been diagnosed with B-cell chronic lymphocytic leukemia (CLL) years prior to the MTB presentation. GIST had been diagnosed 1 month earlier. After structured clinical annotation of the molecular alterations and interdisciplinary discussion, we considered BRAF/KIT co-mutation unlikely in a treatment-naïve GIST. Discordant variant allele frequencies furthermore suggested a second malignancy. NGS of a CLL sample revealed the identical class 2 BRAF alteration, thus supporting admixture of CLL cells in the paragastric mass, leading to the detection of 2 alterations. Following the MTB recommendation, the patient received imatinib and had a radiographic response. Structured annotation and interdisciplinary discussion in specialized tumor boards facilitate the clinical management of complex molecular findings. Coexisting malignancies and clonal hematopoiesis warrant consideration in case of complex and uncommon molecular findings.
PubMed: 38886160
DOI: 10.1093/oncolo/oyae137 -
The Oncologist Jun 2024Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare neoplasms with an increasing annual incidence and prevalence. Many are metastatic at presentation or...
BACKGROUND
Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare neoplasms with an increasing annual incidence and prevalence. Many are metastatic at presentation or recur following surgical resection and require systemic therapy, for which somatostatin analogs such as octreotide or lanreotide comprise typical first-line therapies. Nonetheless, treatment options remain limited. Epigenetic processes such as histone modifications have been implicated in malignant transformation and progression. In this study, we evaluated the anti-proliferative effects of a histone deacetylase (HDAC) inhibitor, entinostat, which was computationally predicted to show anti-cancer activity, as confirmed in in vitro and in vivo models of GEP-NETs.
METHODS
This was a phase II study to evaluate the efficacy and safety of entinostat in patients with relapsed or refractory abdominal NETs. The primary objective was to estimate the objective response rate to entinostat. Additionally, with each patient as his/her own control we estimated the rates of tumor growth prior to enrollment on study and while receiving entinostat. Patients received 5 mg entinostat weekly until disease progression or intolerable toxicity. The dose could be changed to 10 mg biweekly for patients who did not experience grade ≥ 2 treatment-related adverse events (AEs) in cycle 1, but was primarily administered at the starting 5 mg weekly dose.
RESULTS
The study enrolled only 5 patients due to early termination by the drug sponsor. The first patient that enrolled had advanced disease and died within days of enrollment before follow-up imaging due to a grade 5 AE unrelated to study treatment and was considered non-evaluable. Best RECIST response for the remaining 4 patients was stable disease (SD) with time on study of 154+, 243, 574, and 741 days. With each patient as his/her own control, rates of tumor growth on entinostat were markedly reduced with rates 20%, 33%, 54%, and 68% of the rates prior to enrollment on study. Toxicities possibly or definitely related to entinostat included grade 2/3 neutrophil count decrease [2/4 (50%)/ 2/4 (50%)], grade 3 hypophosphatemia [1/4, (25%)], grade 1/2 fatigue [1/4 (25%)/ 2/4 (50%)], and other self-limiting grade 1/2 AEs.
CONCLUSION
In the treatment of relapsed or refractory abdominal NETs, entinostat 5 mg weekly led to prolonged SD and reduced the rate of tumor growth by 32% to 80% with an acceptable safety profile (ClinicalTrials.gov Identifier: NCT03211988).
PubMed: 38886159
DOI: 10.1093/oncolo/oyae118 -
The Oncologist Jun 2024Immune checkpoint inhibitors (ICIs) have revolutionized cancer care with incredible reductions in mortality. One of the most devastating complications of treatment is...
BACKGROUND
Immune checkpoint inhibitors (ICIs) have revolutionized cancer care with incredible reductions in mortality. One of the most devastating complications of treatment is ICI-related pneumonitis (ICI-p). Despite this, little is known regarding risk factors for severe pneumonitis and treatment effectiveness of various therapeutic options for steroid-refractory disease. To address this, we conducted a retrospective study on patients with cancer who developed ICI-p.
METHODS
We examined consecutive patients who received ICIs and developed ICI-p. Risk factors of interest for severe disease and steroid-refractory ICI-p, including pre-treatment pulmonary function tests (PFTs) and chest imaging, were compared between patients with severe (grades 3-5) and mild (grades 1-2) pneumonitis. The clinical and treatment courses for patients with steroid-refractory ICI-p were recorded.
RESULTS
A total of 132 patients developed ICI-p, with 60 patients having mild and 72 with severe disease. We found that lower forced vital capacity percent predicted (66.24 vs 85.05, P = .05), lower total lung capacity percent predicted (85.23 vs 99.71, P = .13), and specific radiographic patterns on pre-treatment chest imaging were predictors of severe disease. Initial corticosteroid dose of less than 1 milligram per kilogram prednisone equivalent (P = .14) was correlated with partially steroid-responsive or steroid-refractory ICI-p. Ten patients had steroid refractory ICI-p, and those who received IVIG alone as the immune suppressant beyond corticosteroids had improved survival (P = 05).
CONCLUSIONS
We are the first to identify pre-treatment PFTs and chest imaging abnormalities as risk factors for severe ICI-p. We also found that lower corticosteroid doses were associated with partially steroid-responsive and steroid-refractory ICI-p. Larger, prospective studies are needed to validate our results.
PubMed: 38886156
DOI: 10.1093/oncolo/oyae147 -
The Oncologist Jun 2024Sarcopenia or skeletal muscle depletion is a poor prognostic factor for gastric cancer (GC). However, existing cutoff values of skeletal muscle index (SMI) for defining...
BACKGROUND
Sarcopenia or skeletal muscle depletion is a poor prognostic factor for gastric cancer (GC). However, existing cutoff values of skeletal muscle index (SMI) for defining sarcopenia have been found to have limitations when clinically applied. This study aimed to determine the optimal cutoff for SMI to predict severe toxicities of chemotherapy and overall survival (OS) in patients with advanced GC.
METHODS
Patients with metastatic gastric adenocarcinoma who received first-line palliative chemotherapy between January 2014 and December 2021 at Queen Mary Hospital, Hong Kong, were included in this study. The SMI was determined via a pre-chemotherapy computed tomography scan. Optimal cutoff points of SMI were identified by recursive partitioning analysis. Univariate and multivariate analyses evaluating risk factors of severe chemotherapy toxicities and OS were also performed.
RESULTS
A total of 158 patients (male: 108 (68.4%), median age: 65.3) were included. The SMI cutoff to define low SMI was ≤33 cm2/m2 for males and ≤28 cm2/m2 for females; 30 patients (19.0%) had low SMI. Patients with low SMI had a higher incidence of hematological toxicities (63.3% vs 32.0%, P = .001) and non-hematological toxicities (66.7% vs 36.7%, P = .003). Multivariable analysis indicated that low SMI and low serum albumin (≤28 g/L) were independent predictive factors of hematological toxicity, while low SMI and neutrophil-lymphocyte ratio ≥5 were predictive factors of non-hematological toxicity. Moreover, patients with low SMI had a significantly shorter OS (P = .011), lower response rate to chemotherapy (P = .045), and lower utilization of subsequent lines of treatment (P < .001).
CONCLUSIONS
Using pre-chemotherapy SMI cutoff (≤33 cm2/m2 for males and 28 cm2/m2 for females) one can identify individuals with a higher risk of severe chemotherapy toxicities and worse prognosis.
PubMed: 38885304
DOI: 10.1093/oncolo/oyae123 -
The Oncologist Jun 2024The activity of PARP inhibitors (PARPi) in patients with homologous recombination repair (HRR) mutations and metastatic castration-resistant prostate cancer has been...
TRIUMPH: phase II trial of rucaparib monotherapy in patients with metastatic hormone-sensitive prostate cancer harboring germline homologous recombination repair gene mutations.
BACKGROUND
The activity of PARP inhibitors (PARPi) in patients with homologous recombination repair (HRR) mutations and metastatic castration-resistant prostate cancer has been established. We hypothesized that the benefit of PARPi can be maintained in the absence of androgen deprivation therapy (ADT) in an HRR-mutated population. We report the results of a phase II clinical trial of rucaparib monotherapy in patients with metastatic hormone-sensitive prostate cancer (mHSPC).
METHODS
This was a multi-center, single-arm phase II trial (NCT03413995) for patients with asymptomatic, mHSPC. Patients were required to have a pathogenic germline mutation in an HRR gene for eligibility. All patients received rucaparib 600 mg by mouth twice daily, without androgen deprivation. The primary endpoint was a confirmed PSA50 response rate.
RESULTS
Twelve patients were enrolled, 7 with a BRCA1/2 mutation and 5 with a CHEK2 mutation. The confirmed PSA50 response rate to rucaparib was 41.7% (N = 5/12, 95% CI: 15.2-72.3%, one-sided P = .81 against the 50% null), which did not meet the pre-specified efficacy boundary to enroll additional patients. In patients with measurable disease, the objective response rate was 60% (N = 3/5), all with a BRCA2 mutation. The median radiographic progression-free survival on rucaparib was estimated at 12.0 months (95% CI: 8.0-NR months). The majority of adverse events were grade ≤2, and expected.
CONCLUSION
Rucaparib can induce clinical responses in a biomarker-selected metastatic prostate cancer population without concurrent ADT. However, the pre-specified efficacy threshold was not met, and enrolment was truncated. Although durable responses were observed in a subset of patients, further study of PARPi treatment without ADT in mHSPC is unlikely to change clinical practice.
PubMed: 38885246
DOI: 10.1093/oncolo/oyae120 -
Clinical and Translational Radiation... Jul 2024Aim of the present study is to characterize a deep learning-based auto-segmentation software (DL) for prostate cone beam computed tomography (CBCT) images and to...
PURPOSE
Aim of the present study is to characterize a deep learning-based auto-segmentation software (DL) for prostate cone beam computed tomography (CBCT) images and to evaluate its applicability in clinical adaptive radiation therapy routine.
MATERIALS AND METHODS
Ten patients, who received exclusive radiation therapy with definitive intent on the prostate gland and seminal vesicles, were selected. Femoral heads, bladder, rectum, prostate, and seminal vesicles were retrospectively contoured by four different expert radiation oncologists on patients CBCT, acquired during treatment. Consensus contours (CC) were generated starting from these data and compared with those created by DL with different algorithms, trained on CBCT (DL-CBCT) or computed tomography (DL-CT). Dice similarity coefficient (DSC), centre of mass (COM) shift and volume relative variation (VRV) were chosen as comparison metrics. Since no tolerance limit can be defined, results were also compared with the inter-operator variability (IOV), using the same metrics.
RESULTS
The best agreement between DL and CC was observed for femoral heads (DSC of 0.96 for both DL-CBCT and DL-CT). Performance worsened for low-contrast soft tissue organs: the worst results were found for seminal vesicles (DSC of 0.70 and 0.59 for DL-CBCT and DL-CT, respectively). The analysis shows that it is appropriate to use algorithms trained on the specific imaging modality. Furthermore, the statistical analysis showed that, for almost all considered structures, there is no significant difference between DL-CBCT and human operator in terms of IOV.
CONCLUSIONS
The accuracy of DL-CBCT is in accordance with CC; its use in clinical practice is justified by the comparison with the inter-operator variability.
PubMed: 38884004
DOI: 10.1016/j.ctro.2024.100796 -
Journal of Thoracic Disease May 2024Sarcomas of the chest wall are rare and their current treatment regimen is diverse and complex due to the heterogeneity of these tumors as well as the variations in... (Review)
Review
Sarcomas of the chest wall are rare and their current treatment regimen is diverse and complex due to the heterogeneity of these tumors as well as the variations in tumor location and extent. They only account for 0.04% of newly diagnosed cancers of whom about 45% comprise soft tissue sarcomas. Larger cohort studies are scarce and often focus on one specific treatment item. We therefore aim to provide helicopter view for clinicians treating patients with sarcomas of the chest wall, focusing mainly on soft tissue sarcomas. This overview includes the value of neoadjuvant systemic or radiotherapy, surgical resection, approaches for thoracic wall reconstruction, and the need for follow-up. Provided the heterogeneity and relative rarity, we recommend that treatment decisions in soft tissue sarcoma of the chest wall are discussed in a multidisciplinary tumor board at a reference sarcoma center or within sarcoma networks to ensure personalized, rational decision making. A surgical oncologist specialized in sarcoma surgery is crucial, and for extensive resections involving the thoracic cavity we recommend involvement of a thoracic surgeon. In addition, a specialized medical- and radiation oncologist as well as a plastic surgeon is required to ensure the best multimodality treatment plan to optimize patient outcome.
PubMed: 38883634
DOI: 10.21037/jtd-23-1149 -
Journal of Pharmacy & Bioallied Sciences Apr 2024Tumor budding is a distinctive phenomenon which involves the presence of small clusters or individual cancer cells at the invasive front of tumors. Tumor budding has...
INTRODUCTION AND AIM
Tumor budding is a distinctive phenomenon which involves the presence of small clusters or individual cancer cells at the invasive front of tumors. Tumor budding has garnered attention due to its potential implications for prognosis, treatment strategies, and our understanding of cancer progression. Our aim is to study the distribution of tumor buds and its scoring in patients with infiltrating breast carcinoma and to associate with other histopathological parameters like the size of the tumor, its grade, lymphovascular invasion, and lymph node metastasis.
MATERIALS AND METHODS
This was a study analyzing the data of 70 resected specimens of primary breast carcinomas and providing a descriptive overview. Tumor budding was recognized, counted, and graded in hematoxylin and eosin slides. The cases were classified as low (0-4), intermediate (5-9), and high (≥10 buds) based on the count of tumor buds. Tumor budding has significant correlation with tumor grade and tumor size.
RESULTS
Of the 70 cases, 60 cases (85.71%) were diagnosed as invasive ductal carcinoma NOS. The majority [38 (54.28%)] of the cases showed an intermediate tumor budding score of 5-9/10 HPF.
CONCLUSION
Evaluation of tumor budding allows pathologists and oncologists to gather valuable information about the tumor's biological aggressiveness and potential for metastasis. It also helps in better risk stratification of patients, enabling a more personalized and tailored approach to treatment planning. In conclusion, assessing tumor budding in breast carcinoma holds significant clinical importance in the management and prognosis of this disease.
PubMed: 38882784
DOI: 10.4103/jpbs.jpbs_910_23 -
Journal of Registry Management 2024The Veterans Health Administration (VHA) is a leader in generating transformational research across the cancer care continuum. Given the extensive body of cancer-related...
OBJECTIVES
The Veterans Health Administration (VHA) is a leader in generating transformational research across the cancer care continuum. Given the extensive body of cancer-related literature utilizing VHA data, our objectives are to: (1) describe the VHA data sources available for conducting cancer-related research, and (2) discuss examples of published cancer research using each data source.
METHODS
We identified commonly used data sources within the VHA and reviewed previously published cancer-related research that utilized these data sources. In addition, we reviewed VHA clinical and health services research web pages and consulted with a multidisciplinary group of cancer researchers that included hematologist/oncologists, health services researchers, and epidemiologists.
RESULTS
Commonly used VHA cancer data sources include the Veterans Affairs (VA) Cancer Registry System, the VA Central Cancer Registry (VACCR), the Corporate Data Warehouse (CDW)-Oncology Raw Domain (subset of data within the CDW), and the VA Cancer Care Cube (Cube). While no reference standard exists for cancer case ascertainment, the VACCR provides a systematic approach to ensure the complete capture of clinical history, cancer diagnosis, and treatment. Like many population-based cancer registries, a significant time lag exists due to constrained resources, which may make it best suited for historical epidemiologic studies. The CDW-Oncology Raw Domain and the Cube contain national information on incident cancers which may be useful for case ascertainment and prospective recruitment; however, additional resources may be needed for data cleaning.
CONCLUSIONS
The VHA has a wealth of data sources available for cancer-related research. It is imperative that researchers recognize the advantages and disadvantages of each data source to ensure their research questions are addressed appropriately.
Topics: Humans; United States; United States Department of Veterans Affairs; Registries; Neoplasms; Veterans Health; Information Sources
PubMed: 38881982
DOI: No ID Found -
Translational Cancer Research May 2024Programmed cell death-1 (PD-1) inhibitors and anti-angiogenic drugs have become a hotspot in research of anti-tumor programs; however, they can also cause some rare...
BACKGROUND
Programmed cell death-1 (PD-1) inhibitors and anti-angiogenic drugs have become a hotspot in research of anti-tumor programs; however, they can also cause some rare drug-related adverse reactions. Immune checkpoint inhibitors (ICIs) cause adverse reactions in the body, collectively known as immune-related adverse events (irAEs). Ocular side effects can occur in both targeted and immunotherapy patients, including dry eye, blurred vision, uveitis, conjunctivitis, retinopathy, or thyroid eye disease. To our knowledge, this is the first case report describing corneal ulcers secondary to dry eye in a patient treated with the combination of PD-1 inhibitor sintilimab and multi-targeted receptor tyrosine kinase inhibitor (TKI) anlotinib.
CASE DESCRIPTION
A 65-year-old woman with non-small cell lung cancer (NSCLC) and bone metastases, without pre-existing ocular conditions, experienced mild dry eye symptoms 1 month following treatment with sintilimab (200 mg q3w) in combination with anlotinib (12 mg q3w). Unrelieved dry eye symptoms occurred after the third cycle of chemotherapy, and she was diagnosed with dry eye syndrome. Subsequently, she received corneal protective lens, sodium hyaluronate eye drops, and prednisone treatment. Her corneal epithelial damage did not improve significantly, and within the following 2 months, her vision decreased in both eyes and progressed to bilateral corneal ulcers. Oral administration of sintilimab and anlotinib was interrupted, and treatments such as corticosteroids, anti-inflammatory drugs, and corneal repair were administered; however, both eyes presented with corneal subepithelial defect and corneal scarring. Due to a shortage of donors, no corneal transplantation surgery could be performed.
CONCLUSIONS
The development of corneal epithelial disorders in patients receiving target therapy and immunotherapy may not be reversed by reducing its dose. Although the condition is controlled with the use of glucocorticoids, some eye side effects cannot be cured. The timely detection and intervention of adverse effects of anti-tumor drugs by oncologists and ophthalmologists is critical for rational prescription. Ophthalmologists should be aware of eye side effects in patients using immunotherapy to ensure appropriate treatment and minimize potential eye complications such as dry eye, conjunctivitis, etc.
PubMed: 38881937
DOI: 10.21037/tcr-23-1952