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1.
Future Oncol ; 18(10): 1185-1198, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-2065335

ABSTRACT

Cabozantinib inhibits multiple receptor tyrosine kinases, including the TAM kinase family, and may enhance response to immune checkpoint inhibitors. One cohort of the ongoing phase Ib COSMIC-021 study (NCT03170960) evaluating cabozantinib plus the PD-L1 inhibitor atezolizumab in men with metastatic castration-resistant prostate cancer (mCRPC) that has progressed in soft tissue on/after enzalutamide and/or abiraterone treatment for metastatic disease has shown promising efficacy. Here, we describe the rationale and design of a phase III trial of cabozantinib plus atezolizumab versus a second novel hormone therapy (NHT) in patients who have previously received an NHT for mCRPC, metastatic castration-sensitive PC or nonmetastatic CRPC and have measurable visceral disease and/or extrapelvic adenopathy - a population with a significant unmet need for treatment options. Trial Registration Clinical Trial Registration: NCT04446117 (ClinicalTrials.gov) Registered on 24 June 2020.


Subject(s)
Adenocarcinoma/drug therapy , Anilides/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Agents, Hormonal/therapeutic use , Immune Checkpoint Inhibitors/therapeutic use , Prostatic Neoplasms, Castration-Resistant/drug therapy , Pyridines/therapeutic use , Adenocarcinoma/pathology , Androstenes/therapeutic use , Benzamides/therapeutic use , Humans , Male , Neoplasm Metastasis , Nitriles/therapeutic use , Phenylthiohydantoin/therapeutic use , Prostatic Neoplasms, Castration-Resistant/pathology , Receptor Protein-Tyrosine Kinases/antagonists & inhibitors
3.
Proc Natl Acad Sci U S A ; 119(34): e2207841119, 2022 08 23.
Article in English | MEDLINE | ID: covidwho-1991768

ABSTRACT

The targeted delivery of messenger RNA (mRNA) to desired organs remains a great challenge for in vivo applications of mRNA technology. For mRNA vaccines, the targeted delivery to the lymph node (LN) is predicted to reduce side effects and increase the immune response. In this study, we explored an endogenously LN-targeting lipid nanoparticle (LNP) without the modification of any active targeting ligands for developing an mRNA cancer vaccine. The LNP named 113-O12B showed increased and specific expression in the LN compared with LNP formulated with ALC-0315, a synthetic lipid used in the COVID-19 vaccine Comirnaty. The targeted delivery of mRNA to the LN increased the CD8+ T cell response to the encoded full-length ovalbumin (OVA) model antigen. As a result, the protective and therapeutic effect of the OVA-encoding mRNA vaccine on the OVA-antigen-bearing B16F10 melanoma model was also improved. Moreover, 113-O12B encapsulated with TRP-2 peptide (TRP2180-188)-encoding mRNA also exhibited excellent tumor inhibition, with the complete response of 40% in the regular B16F10 tumor model when combined with anti-programmed death-1 (PD-1) therapy, revealing broad application of 113-O12B from protein to peptide antigens. All the treated mice showed long-term immune memory, hindering the occurrence of tumor metastatic nodules in the lung in the rechallenging experiments that followed. The enhanced antitumor efficacy of the LN-targeting LNP system shows great potential as a universal platform for the next generation of mRNA vaccines.


Subject(s)
Cancer Vaccines , Nanoparticles , Neoplasms , mRNA Vaccines , Amino Alcohols , Animals , Antigens/metabolism , CD8-Positive T-Lymphocytes , Cancer Vaccines/therapeutic use , Decanoates , Immunologic Memory , Liposomes , Lymph Nodes , Mice , Neoplasm Metastasis/prevention & control , Neoplasms/therapy , Ovalbumin , mRNA Vaccines/therapeutic use
4.
Front Immunol ; 12: 798276, 2021.
Article in English | MEDLINE | ID: covidwho-1606542

ABSTRACT

Effects of initiation of programmed-death-protein 1 (PD1) blockade during active SARS-CoV-2 infection on antiviral immunity, COVID-19 course, and underlying malignancy are unclear. We report on the management of a male in his early 40s presenting with highly symptomatic metastatic lung cancer and active COVID-19 pneumonia. After treatment initiation with pembrolizumab, carboplatin, and pemetrexed, the respiratory situation initially worsened and high-dose corticosteroids were initiated due to suspected pneumonitis. After improvement and SARS-CoV-2 clearance, anti-cancer treatment was resumed without pembrolizumab. Immunological analyses with comparison to otherwise healthy SARS-CoV-2-infected ambulatory patients revealed a strong humoral immune response with higher levels of SARS-CoV-2-reactive IgG and neutralizing serum activity. Additionally, sustained increase of Tfh as well as activated CD4+ and CD8+ T cells was observed. Sequential CT scans showed regression of tumor lesions and marked improvement of the pulmonary situation, with no signs of pneumonitis after pembrolizumab re-challenge as maintenance. At the latest follow-up, the patient is ambulatory and in ongoing partial remission on pembrolizumab. In conclusion, anti-PD1 initiation during active COVID-19 pneumonia was feasible and cellular and humoral immune responses to SARS-CoV-2 appeared enhanced in our hospitalized patient. However, distinguishing COVID-19-associated changes from anti-PD1-associated immune-related pneumonitis posed a considerable clinical, radiographic, and immunologic challenge.


Subject(s)
Adrenal Cortex Hormones/therapeutic use , COVID-19 Drug Treatment , Carcinoma, Non-Small-Cell Lung/drug therapy , Immune Checkpoint Inhibitors/therapeutic use , Lung Neoplasms/drug therapy , SARS-CoV-2/drug effects , Adult , CD8-Positive T-Lymphocytes/drug effects , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/virology , COVID-19/complications , COVID-19/immunology , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/immunology , Carcinoma, Non-Small-Cell Lung/complications , Carcinoma, Non-Small-Cell Lung/immunology , Humans , Immunity, Humoral/drug effects , Immunity, Humoral/immunology , Lung Neoplasms/complications , Lung Neoplasms/immunology , Male , Neoplasm Metastasis , Pneumonia/immunology , Pneumonia/prevention & control , Pneumonia/virology , SARS-CoV-2/immunology
5.
Cancer Med ; 10(22): 8058-8070, 2021 11.
Article in English | MEDLINE | ID: covidwho-1525414

ABSTRACT

BACKGROUND: Exercise may improve clinical and quality of life outcomes for men with prostate cancer. No randomized controlled trials (RCTs) have examined the feasibility, safety, and acceptability of remote exercise training in men with metastatic castrate-resistant prostate cancer (mCRPC). METHODS: We conducted a pilot RCT (1:1:1 aerobic or resistance exercise 3x/week or usual care) to determine the feasibility, safety, and acceptability of remotely monitored exercise over 12 weeks in 25 men with mCRPC. A prescribed exercise program was based on baseline testing including high- and moderate-intensity aerobic exercise or resistance exercise completed at a local exercise facility. Feasibility was based on attendance, adherence, and tolerance; safety on adverse events; and acceptability on participant interviews. RESULTS: Between March 2016 and March 2020, 25 patients were randomized (8 aerobic, 7 resistance, and 10 control). Twenty-three men (82%) completed the 12-week study. Men who completed the remote intervention attempted 90% and 96% of prescribed aerobic and resistance training sessions, respectively, and 86% and 88% of attempted sessions were completed as or more than prescribed. We observed changes in performance tests that corresponded with the exercise prescription. No safety concerns were identified. Ninety percent of participants interviewed were satisfied with the program and would recommend it to others. CONCLUSIONS: Remotely monitored exercise training is feasible, safe, and acceptable in men with mCRPC; there was no difference in these outcomes by mode of exercise. Through this research, we provide direction and rationale for future studies of exercise and clinical outcomes in patients with metastatic prostate cancer.


Subject(s)
Exercise/trends , Prostatic Neoplasms, Castration-Resistant/therapy , Aged , Aged, 80 and over , Feasibility Studies , Humans , Male , Middle Aged , Neoplasm Metastasis , Pilot Projects
7.
Int J Mol Sci ; 22(14)2021 Jul 06.
Article in English | MEDLINE | ID: covidwho-1502438

ABSTRACT

Neutrophils form sticky web-like structures known as neutrophil extracellular traps (NETs) as part of innate immune response. NETs are decondensed extracellular chromatin filaments comprising nuclear and cytoplasmic proteins. NETs have been implicated in many gastrointestinal diseases including colorectal cancer (CRC). However, the regulatory mechanisms of NET formation and potential pharmacological inhibitors in the context of CRC have not been thoroughly discussed. In this review, we intend to highlight roles of NETs in CRC progression and metastasis as well as the potential of targeting NETs during colon cancer therapy.


Subject(s)
Colorectal Neoplasms/immunology , Colorectal Neoplasms/pathology , Extracellular Traps/immunology , Neutrophils/immunology , Neutrophils/pathology , Animals , Disease Progression , Extracellular Traps/physiology , Humans , Neoplasm Metastasis/immunology
8.
J Immunother Cancer ; 9(7)2021 07.
Article in English | MEDLINE | ID: covidwho-1476741

ABSTRACT

Cytokine release syndrome (CRS) is a well-described immune-related adverse event following chimeric antigen receptor T-cell therapy, but has rarely been reported following anti-programmed death ligand-1 therapy. We report the case of a 55-year-old man with metastatic lung adenocarcinoma who presented with fever, chills and hypotension. Initial labs were notable for highly elevated serum ferritin levels and mildly elevated triglyceride levels. He was ultimately diagnosed with pembrolizumab-induced CRS complicated by multiorgan failure. The patient was treated with steroids and tocilizumab with normalization of inflammatory markers and resolution of renal failure. This case not only highlights the importance of considering CRS in patients who have developed multiorgan failure after immune checkpoint inhibitor therapy, but also demonstrates clinical similarities between CRS and other hyperinflammatory states such as hemophagocytic lymphohistiocytosis.


Subject(s)
Adenocarcinoma of Lung/drug therapy , Antibodies, Monoclonal, Humanized/adverse effects , Antineoplastic Agents, Immunological/therapeutic use , Cytokine Release Syndrome/chemically induced , Adenocarcinoma of Lung/secondary , Antibodies, Monoclonal, Humanized/pharmacology , Antineoplastic Agents, Immunological/pharmacology , Humans , Male , Middle Aged , Neoplasm Metastasis
9.
Proc Natl Acad Sci U S A ; 118(41)2021 10 12.
Article in English | MEDLINE | ID: covidwho-1450313

ABSTRACT

Cancer therapy reduces tumor burden via tumor cell death ("debris"), which can accelerate tumor progression via the failure of inflammation resolution. Thus, there is an urgent need to develop treatment modalities that stimulate the clearance or resolution of inflammation-associated debris. Here, we demonstrate that chemotherapy-generated debris stimulates metastasis by up-regulating soluble epoxide hydrolase (sEH) and the prostaglandin E2 receptor 4 (EP4). Therapy-induced tumor cell debris triggers a storm of proinflammatory and proangiogenic eicosanoid-driven cytokines. Thus, targeting a single eicosanoid or cytokine is unlikely to prevent chemotherapy-induced metastasis. Pharmacological abrogation of both sEH and EP4 eicosanoid pathways prevents hepato-pancreatic tumor growth and liver metastasis by promoting macrophage phagocytosis of debris and counterregulating a protumorigenic eicosanoid and cytokine storm. Therefore, stimulating the clearance of tumor cell debris via combined sEH and EP4 inhibition is an approach to prevent debris-stimulated metastasis and tumor growth.


Subject(s)
Eicosanoids/metabolism , Epoxide Hydrolases/biosynthesis , Macrophages/immunology , Neoplasm Metastasis/pathology , Receptors, Prostaglandin E, EP4 Subtype/biosynthesis , Animals , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Carcinoma, Hepatocellular/pathology , Cell Death/drug effects , Cell Line, Tumor , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/prevention & control , Cytokines/metabolism , Hep G2 Cells , Humans , Liver Neoplasms/drug therapy , Liver Neoplasms/pathology , Male , Mice , Mice, Inbred C57BL , Neoplasm Metastasis/prevention & control , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/pathology , Phagocytosis/immunology , RAW 264.7 Cells
10.
Urology ; 155: 179-185, 2021 09.
Article in English | MEDLINE | ID: covidwho-1411044

ABSTRACT

OBJECTIVE: To determine the attitudes and education regarding surgical castration in men receiving androgen deprivation therapy (ADT) for metastatic prostate cancer (mCaP). METHODS: We identified 142 patients receiving ADT for mCaP at our institution without prior orchiectomy who were then sent 2 surveys via mail: (1) A questionnaire to assess knowledge and understanding of ADT treatment alternatives and (2) the functional assessment of cancer therapy - prostate (FACT-P) questionnaire which determines health-related quality of life (HRQOL). Two cohorts were created based on the answer to "would you be interested in surgical orchiectomy?" and demographic, CaP and HRQOL were compared between the surgical castration yes (SC+) and surgical castration no (SC-) cohorts. A second analysis identified predictors of worse HRQOL. RESULTS: Of 68 (47.9%) patients that responded to the survey, only 39 (59.1%) recalled a discussion regarding treatment alternatives to ADT and only 22 (33.3%) recalled a discussion regarding orchiectomy. There were 24 (40.0%) patients that stated interest in undergoing orchiectomy (SC+) as an alternative to ADT with the only independent risk factor being "…bother from the number of clinical appointments required for ADT…" Patients most bothered by side effects and cosmetic changes associated with ADT reported lower HRQOL scores on the FACT-P. CONCLUSIONS: Few men on ADT knew about surgical alternatives, implying that educational deficits may be a significant factor in the decline in the utilization of orchiectomy. Changes in healthcare economics, utilization and delivery brought on by a global pandemic should warrant a fresh look at the use of surgical castration.


Subject(s)
Health Knowledge, Attitudes, Practice , Orchiectomy/psychology , Prostatic Neoplasms/therapy , Quality of Life , Aged , Androgen Antagonists/therapeutic use , Humans , Male , Neoplasm Metastasis , Patient Acceptance of Health Care , Patient Education as Topic , Prostatic Neoplasms/pathology , Surveys and Questionnaires
11.
J Mammary Gland Biol Neoplasia ; 26(3): 221-226, 2021 09.
Article in English | MEDLINE | ID: covidwho-1375665

ABSTRACT

The twelfth annual workshop of the European Network for Breast Development and Cancer focused on methods in mammary gland biology and breast cancer, was scheduled to take place on March 26-28, 2020, in Weggis, Switzerland. Due to the COVID-19 pandemic, the meeting was rescheduled twice and eventually happened as a virtual meeting on April 22 and 23, 2021. The main topics of the meeting were branching and development of the mammary gland, tumor microenvironment, circulating tumor cells, tumor dormancy and breast cancer metastasis. Novel and unpublished findings related to these topics were presented, with a particular focus on the methods used to obtain them. Virtual poster sessions were a success, with many constructive and fruitful interactions between researchers and covered many areas of mammary gland biology and breast cancer.


Subject(s)
Biomedical Research/methods , Breast Neoplasms/pathology , Mammary Glands, Human/pathology , Biomarkers, Tumor/metabolism , Breast Neoplasms/diagnosis , Breast Neoplasms/metabolism , Breast Neoplasms/therapy , Combined Modality Therapy , Europe , Female , Humans , Mammary Glands, Human/growth & development , Mammary Glands, Human/metabolism , Neoplasm Metastasis , Neoplasm Staging , Neoplastic Cells, Circulating , Prognosis , Tumor Microenvironment
12.
J Investig Med ; 69(6): 1145-1147, 2021 08.
Article in English | MEDLINE | ID: covidwho-1327694
13.
Int J Radiat Oncol Biol Phys ; 109(3): 756-763, 2021 03 01.
Article in English | MEDLINE | ID: covidwho-1318870

ABSTRACT

PURPOSE: Fewer attendances for radiation therapy results in increased efficiency and less foot traffic within a radiation therapy department. We investigated outcomes after single-fraction (SF) stereotactic body radiation therapy (SBRT) in patients with oligometastatic disease. METHODS AND MATERIALS: Between February 2010 and June 2019, patients who received SF SBRT to 1 to 5 sites of oligometastatic disease were included in this retrospective study. The primary objective was to describe patterns of first failure after SBRT. Secondary objectives included overall survival (OS), progression-free survival (PFS), high-grade treatment-related toxicity (Common Terminology Criteria for Adverse Events grade ≥3), and freedom from systemic therapy (FFST). RESULTS: In total, 371 patients with 494 extracranial oligometastases received SF SBRT ranging from 16 Gy to 28 Gy. The most common primary malignancies were prostate (n = 107), lung (n = 63), kidney (n = 52), gastrointestinal (n = 51), and breast cancers (n = 42). The median follow-up was 3.1 years. The 1-, 3-, and 5-year OS was 93%, 69%, and 55%, respectively; PFS was 48%, 19%, and 14%, respectively; and FFST was 70%, 43%, and 35%, respectively. Twelve patients (3%) developed grade 3 to 4 treatment-related toxicity, with no grade 5 toxicity. As the first site of failure, the cumulative incidence of local failure (irrespective of other failures) at 1, 3 and 5 years was 4%, 8%, and 8%, respectively; locoregional relapse at the primary was 10%, 18%, and 18%, respectively; and distant failure was 45%, 66%, and 70%, respectively. CONCLUSIONS: SF SBRT is safe and effective, and a significant proportion of patients remain FFST for several years after therapy. This approach could be considered in resource-constrained or bundled-payment environments. Locoregional failure of the primary site is the second most common pattern of failure, suggesting a role for optimization of primary control during metastasis-directed therapy.


Subject(s)
Neoplasm Metastasis/radiotherapy , Radiosurgery/methods , Adult , Aged , Aged, 80 and over , COVID-19/epidemiology , Female , Humans , Male , Middle Aged , Neoplasms/radiotherapy , Neoplasms/surgery , Pandemics , Progression-Free Survival , Radiation Injuries/pathology , Radiosurgery/adverse effects , Radiotherapy Dosage , Retrospective Studies , Salvage Therapy , Treatment Failure , Young Adult
14.
Semin Nucl Med ; 51(5): 474-484, 2021 09.
Article in English | MEDLINE | ID: covidwho-1254012

ABSTRACT

There are a number of normal variants and pitfalls which are important to consider when evaluating F-18 Fluorodeoxyglucose (FDG) with Positron Emission Tomography (PET) in breast cancer patients. Although FDG-PET is not indicated for the initial diagnosis of breast cancer, focally increased glucose metabolism within breast tissue represents a high likelihood for a neoplastic process and requires further evaluation. Focally increased glucose metabolism is not unique to breast cancer. Other malignancies such as lymphoma, metastases from solid tumors as well as inflammatory changes also may demonstrate increased glucose metabolism either within the breast or at other sites throughout the body. Importantly, benign breast disease may also exhibit increased glucose metabolism, limiting the specificity of FDG-PET. Breast cancer has a wide range of metabolic activity attributed to tumor heterogeneity and breast cancer subtype. Intracellular signaling pathways regulating tumor glucose utilization contribute to these pitfalls of PET/CT in breast cancer. The evaluation of axillary lymph nodes by FDG-PET is less accurate than sentinel lymph node procedure, however is very accurate in identifying level II and III axillary lymph node metastases or retropectoral metastases. It is important to note that non-malignant inflammation in lymph nodes are often detected by modern PET/CT technology. Therefore, particular consideration should be given to recent vaccinations, particularly to COVID-19, which can commonly result in increased metabolic activity of axillary nodes. Whole body FDG-PET for staging of breast cancer requires specific attention to physiologic variants of FDG distribution and a careful comparison with co-registered anatomical imaging. The most important pitfalls are related to inflammatory changes including sarcoidosis, sarcoid like reactions, and other granulomatous diseases as well as secondary neoplastic processes.


Subject(s)
Breast Neoplasms/diagnostic imaging , Positron Emission Tomography Computed Tomography/methods , Breast Neoplasms/pathology , Fluorodeoxyglucose F18 , Humans , Neoplasm Metastasis , Neoplasm Staging
15.
J Chemother ; 33(7): 499-508, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1242059

ABSTRACT

The main objective is to define the mortality of patients with cancer admitted to our hospital, their clinical and demographic characteristics, investigate the risk of COVID-19 for patients with cancer, and determine factors that affect the mortality rates of patients with cancer dying of COVID-19. A total of 2401 patients were admitted to our hospital with the diagnosis of COVID-19 from March 11th, 2020, to May 31st, 2020. Ninety-two out of a total of 112 cancer patients were included in this study based on the planned inclusion/exclusion criteria. The clinical, demographic, and laboratory features and treatments provided were studied, and their effect on mortality rates was analyzed. In our study the median age of the patients was 67 years, and 55.4% were male. More than half (56.5%) of our patients had metastasis. The mortality rate was 6.2% in the overall population with COVID-19, whereas it was 23.9% in patients with cancer. The mortality rate in patients with metastasis was statistically significantly higher compared with those without metastasis (34.0% vs. 10.3% P = 0.008). The mortality rate in patients still smoking was statistically significantly higher than in non-smokers (37.5% vs. 12.5% P = 0.033). The mortality rates of patients with high average C-reactive protein (CRP), ferritin, lactate dehydrogenase (LDH), and D-dimer levels were statistically significantly higher than in those without, and the mortality rates of patients with lower average albumin and hemoglobin levels were statistically significantly higher than those without (P < 0.001, P = 0.006, P = 0.041, P < 0.001, P < 0.001, and P = 0.028, respectively). Having metastases concurrent with COVID-19 was a statistically significant factor predictive of prognosis. Also, high CRP, ferritin, LDH, and D-dimer, and low albumin and hemoglobin were related to increased mortality rates. The predictive and prognostic role of possible factors related to prognosis is still unknown and further large, multicenter prospective studies are needed to confirm these results.


Subject(s)
COVID-19/mortality , Neoplasms/mortality , Aged , C-Reactive Protein/analysis , COVID-19/complications , Comorbidity , Female , Ferritins/blood , Fibrin Fibrinogen Degradation Products/analysis , Hospital Mortality , Hospitalization , Humans , L-Lactate Dehydrogenase/blood , Male , Neoplasm Metastasis , Neoplasms/complications , Prognosis , Smoking , Turkey
16.
Am Surg ; 86(11): 1473-1477, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-1067016

ABSTRACT

Regardless of the anatomic site of malignant bowel obstruction leading to the need for palliative intervention, decisions must consider the natural history of the disease, the availability and success of nonsurgical treatments, the individual patient's symptom severity, goals, preferences, quality, and expectancy of life. Therapy for symptoms must remain flexible and individualized because the specific needs of the patient will change as disease progresses. Because strangulation is uncommon, malignant bowel obstruction is usually not a surgical emergency. There is usually time to proceed with deliberate and thoughtful decisions on how best to meet the needs and expectations of the individual patient and family. Providers must be well versed in both surgical and nonsurgical therapeutic options, the natural history of disease, and be active and compassionate providers to foster meaningful ongoing dialogue focused on excellent care even after cure is no longer possible. The palliative triangle not only allows patient, family, and surgeon to effectively utilize the full continuum of care that can be delivered, but also it supports end-of-life decisions when continuity in care matters most. Due to social distancing requirements, the dynamics of communication between patient, family, and surgeon have changed. Zoom, Skype, and FaceTime have become tools in our communication armamentarium.


Subject(s)
Breast Neoplasms/diagnosis , Intestinal Obstruction/etiology , Intestine, Small , Peritoneal Neoplasms/secondary , Biopsy , Breast Neoplasms/epidemiology , COVID-19 , Comorbidity , Fatal Outcome , Female , Humans , Intestinal Obstruction/diagnosis , Intestinal Obstruction/epidemiology , Middle Aged , Neoplasm Metastasis , Pandemics , Peritoneal Neoplasms/diagnosis , Peritoneal Neoplasms/epidemiology , Radiography, Abdominal , SARS-CoV-2
17.
JAMA Netw Open ; 4(1): e2034065, 2021 01 04.
Article in English | MEDLINE | ID: covidwho-1049541

ABSTRACT

Importance: The coronavirus disease 2019 (COVID-19) pandemic has led to treatment delays for many patients with cancer. While published guidelines provide suggestions on which cases are appropriate for treatment delay, there are no good quantitative estimates on the association of delays with tumor control or risk of new metastases. Objectives: To develop a simplified mathematical model of tumor growth, control, and new metastases for cancers with varying doubling times and metastatic potential and to estimate tumor control probability (TCP) and metastases risk as a function of treatment delay interval. Design, Setting, and Participants: This decision analytical model describes a quantitative model for 3 tumors (ie, head and neck, colorectal, and non-small cell lung cancers). Using accepted ranges of tumor doubling times and metastatic development from the clinical literature from 2001 to 2020, estimates of tumor growth, TCP, and new metastases were analyzed for various treatment delay intervals. Main Outcomes and Measures: Risk estimates for potential decreases in local TCP and increases in new metastases with each interval of treatment delay. Results: For fast-growing head and neck tumors with a 2-month treatment delay, there was an estimated 4.8% (95% CI, 3.4%-6.4%) increase in local tumor control risk and a 0.49% (0.47%-0.51%) increase in new distal metastases risk. A 6-month delay was associated with an estimated 21.3% (13.4-30.4) increase in local tumor control risk and a 6.0% (5.2-6.8) increase in distal metastases risk. For intermediate-growing colorectal tumors, there was a 2.1% (0.7%-3.5%) increase in local tumor control risk and a 2.7% (2.6%-2.8%) increase in distal metastases risk at 2 months and a 7.6% (2.2%-14.2%) increase in local tumor control risk and a 24.7% (21.9%-27.8%) increase in distal metastases risk at 6 months. For slower-growing lung tumors, there was a 1.2% (0.0%-2.8%) increase in local tumor control risk and a 0.19% (0.18%-0.20%) increase in distal metastases risk at 2 months, and a 4.3% (0.0%-10.6%) increase in local tumor control risk and a 1.9% (1.6%-2.2%) increase in distal metastases risk at 6 months. Conclusions and Relevance: This study proposed a model to quantify the association of treatment delays with local tumor control and risk of new metastases. The detrimental associations were greatest for tumors with faster rates of proliferation and metastasis. The associations were smaller, but still substantial, for slower-growing tumors.


Subject(s)
Decision Support Techniques , Models, Theoretical , Neoplasm Metastasis/diagnosis , Neoplasms/diagnosis , Time-to-Treatment/statistics & numerical data , COVID-19 , Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Non-Small-Cell Lung/therapy , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/therapy , Head and Neck Neoplasms/diagnosis , Head and Neck Neoplasms/therapy , Humans , Neoplasms/therapy , Risk Assessment , SARS-CoV-2
19.
J Hematol Oncol ; 13(1): 174, 2020 12 11.
Article in English | MEDLINE | ID: covidwho-971766

ABSTRACT

Immunotherapy has been a new standard for recurrent/metastatic head and neck cancers (R/M HNC). One of the prominent characteristics of cancer immunotherapy is the induction of immune memory followed by endured treatment response. However, whether and how a treatment delay would impact on the efficacy of immunotherapy has not been well determined. During the outbreak of COVID-19, a number of cancer patients in Wuhan, the epicenter of the pandemic in China, had experienced long-lasting city lockdown and delay of immunotherapies. Here, we retrospectively analyzed 24 HNC patients treated with immune checkpoint inhibitors in our cancer institute prior to the outbreak of COVID-19 who were re-evaluated after the restoration of regular medical care. Of these 24 patients, 10 patients had achieved complete response (CR) or partial response (PR), 12 patients had achieved stable disease (SD), and 2 patients had received just one cycle treatment without efficacy evaluation before treatment delay. The median delay was 3.75 months (range 1.73-8.17 months). Re-evaluation after treatment delay revealed that ten patients (10/10) who achieved CR or PR, two patients (2/2) who received just one cycle treatment without efficacy evaluation and seven patients (7/12) who achieved SD before outbreak of COVID-19 maintained tumor response after treatment delay. Among the rest five patients who had achieved SD, four patients were re-evaluated as progressive disease (PD) due to treatment delay and one patient died after treatment interruption without re-evaluation. Our results from a small cohort of R/M HNC patients showed that treatment delay of three to four months might have mild, if any, impact on the efficacy of immunotherapy for patients with controlled disease.


Subject(s)
COVID-19/physiopathology , Carcinoma, Squamous Cell/therapy , Head and Neck Neoplasms/therapy , Immune Checkpoint Inhibitors/therapeutic use , Immunotherapy/methods , Adult , Aged , COVID-19/epidemiology , COVID-19/virology , Carcinoma, Squamous Cell/immunology , Carcinoma, Squamous Cell/pathology , China , Female , Head and Neck Neoplasms/immunology , Head and Neck Neoplasms/pathology , Humans , Male , Middle Aged , Neoplasm Metastasis , Neoplasm Recurrence, Local , Pandemics , Retrospective Studies , SARS-CoV-2/physiology , Time-to-Treatment , Treatment Outcome
20.
Cancer Invest ; 39(1): 9-14, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-894477

ABSTRACT

The outbreak of COVID-19 pandemia is a major health worldwide concern. Patients with cancer might have a worse outcome, because of the immunosuppression determined by the tumor itself and anti-cancer treatments, including chemotherapy and radiotherapy. The impact and course of viral infection in patients receiving immunotherapy remains unknown. We report the case of a patient with metastatic melanoma, long responder to anti PD-1 blockade who got infected with Sars CoV-2, recovering without sequelae. A critical review of literature was performed. Limited data available in literature support the possibility to continue the immunotherapy in patients with cancer under control.


Subject(s)
COVID-19/prevention & control , Immune Checkpoint Inhibitors/therapeutic use , Melanoma/drug therapy , SARS-CoV-2/isolation & purification , Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Agents, Immunological/therapeutic use , COVID-19/epidemiology , COVID-19/virology , Humans , Male , Melanoma/pathology , Middle Aged , Neoplasm Metastasis , Pandemics , SARS-CoV-2/physiology
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