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1.
N Engl J Med ; 384(9): 829-841, 2021 03 04.
Article in English | MEDLINE | ID: mdl-33657295

ABSTRACT

BACKGROUND: The efficacy and safety of nivolumab plus cabozantinib as compared with those of sunitinib in the treatment of previously untreated advanced renal-cell carcinoma are not known. METHODS: In this phase 3, randomized, open-label trial, we randomly assigned adults with previously untreated clear-cell, advanced renal-cell carcinoma to receive either nivolumab (240 mg every 2 weeks) plus cabozantinib (40 mg once daily) or sunitinib (50 mg once daily for 4 weeks of each 6-week cycle). The primary end point was progression-free survival, as determined by blinded independent central review. Secondary end points included overall survival, objective response as determined by independent review, and safety. Health-related quality of life was an exploratory end point. RESULTS: Overall, 651 patients were assigned to receive nivolumab plus cabozantinib (323 patients) or sunitinib (328 patients). At a median follow-up of 18.1 months for overall survival, the median progression-free survival was 16.6 months (95% confidence interval [CI], 12.5 to 24.9) with nivolumab plus cabozantinib and 8.3 months (95% CI, 7.0 to 9.7) with sunitinib (hazard ratio for disease progression or death, 0.51; 95% CI, 0.41 to 0.64; P<0.001). The probability of overall survival at 12 months was 85.7% (95% CI, 81.3 to 89.1) with nivolumab plus cabozantinib and 75.6% (95% CI, 70.5 to 80.0) with sunitinib (hazard ratio for death, 0.60; 98.89% CI, 0.40 to 0.89; P = 0.001). An objective response occurred in 55.7% of the patients receiving nivolumab plus cabozantinib and in 27.1% of those receiving sunitinib (P<0.001). Efficacy benefits with nivolumab plus cabozantinib were consistent across subgroups. Adverse events of any cause of grade 3 or higher occurred in 75.3% of the 320 patients receiving nivolumab plus cabozantinib and in 70.6% of the 320 patients receiving sunitinib. Overall, 19.7% of the patients in the combination group discontinued at least one of the trial drugs owing to adverse events, and 5.6% discontinued both. Patients reported better health-related quality of life with nivolumab plus cabozantinib than with sunitinib. CONCLUSIONS: Nivolumab plus cabozantinib had significant benefits over sunitinib with respect to progression-free survival, overall survival, and likelihood of response in patients with previously untreated advanced renal-cell carcinoma. (Funded by Bristol Myers Squibb and others; CheckMate 9ER ClinicalTrials.gov number, NCT03141177.).


Subject(s)
Anilides/administration & dosage , Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Renal Cell/drug therapy , Kidney Neoplasms/drug therapy , Nivolumab/administration & dosage , Pyridines/administration & dosage , Sunitinib/therapeutic use , Adult , Aged , Aged, 80 and over , Anilides/adverse effects , Antineoplastic Agents/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , B7-H1 Antigen/antagonists & inhibitors , Carcinoma, Renal Cell/mortality , Female , Humans , Intention to Treat Analysis , Kidney Neoplasms/mortality , Male , Middle Aged , Nivolumab/adverse effects , Progression-Free Survival , Proportional Hazards Models , Pyridines/adverse effects , Quality of Life , Receptor Protein-Tyrosine Kinases/antagonists & inhibitors , Sunitinib/adverse effects , Survival Analysis
2.
Cancer Immunol Immunother ; 73(8): 142, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38832989

ABSTRACT

BACKGROUND: There is an ongoing debate as to whether sex could be associated with immune checkpoint inhibitor (ICI) benefit. Existing literature data reveal contradictory results, and data on first-line immune combinations are lacking. METHOD: This was a real-world, multicenter, international, observational study to determine the sex effects on the clinical outcomes in metastatic renal cell carcinoma (mRCC) patients treated with immuno-oncology combinations as first-line therapy. RESULTS: A total of 1827 mRCC patients from 71 cancer centers in 21 countries were included. The median OS was 38.7 months (95% CI 32.7-44.2) in the overall study population: 40.0 months (95% CI 32.7-51.6) in males and 38.7 months (95% CI 26.4-41.0) in females (p = 0.202). The median OS was higher in males vs. females in patients aged 18-49y (36.9 months, 95% CI 29.0-51.6, vs. 24.8 months, 95% CI 16.8-40.4, p = 0.426, with + 19% of 2y-OS rate, 72% vs. 53%, p = 0.006), in the clear cell histology subgroup (44.2 months, 95% CI 35.8-55.7, vs. 38.7 months, 95% CI 26.0-41.0, p = 0.047), and in patients with sarcomatoid differentiation (34.4 months, 95% CI 26.4-59.0, vs. 15.3 months, 95% CI 8.9-41.0, p < 0.001). Sex female was an independent negative prognostic factor in the sarcomatoid population (HR 1.72, 95% CI 1.15 - 2.57, p = 0.008). CONCLUSIONS: Although the female's innate and adaptive immunity has been observed to be more active than the male's, women in the subgroup of clear cell histology, sarcomatoid differentiation, and those under 50 years of age showed shorter OS than males.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Carcinoma, Renal Cell/mortality , Carcinoma, Renal Cell/immunology , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/pathology , Female , Male , Middle Aged , Kidney Neoplasms/mortality , Kidney Neoplasms/immunology , Kidney Neoplasms/drug therapy , Kidney Neoplasms/pathology , Adult , Aged , Young Adult , Adolescent , Sex Factors , Immune Checkpoint Inhibitors/therapeutic use , Prognosis , Immunotherapy/methods , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Survival Rate , Aged, 80 and over
3.
Oncologist ; 28(1): 72-79, 2023 01 18.
Article in English | MEDLINE | ID: mdl-36124890

ABSTRACT

BACKGROUND: Despite 4 approved combination regimens in the first-line setting for advanced renal cell carcinoma (aRCC), adverse event (AE) costs data are lacking. MATERIALS AND METHODS: A descriptive analysis on 2 AE cost comparisons was conducted using patient-level data for the nivolumab-based therapies and published data for the pembrolizumab-based therapies. First, grade 3/4 AE costs were compared between nivolumab + ipilimumab vs. nivolumab + cabozantinib vs. pembrolizumab + axitinib using data from the CheckMate 214 (median follow-up [mFU]: 13.1 months), CheckMate 9ER (mFU: 12.8 months), and KEYNOTE-426 (mFU: 12.8 months) trials, respectively. Second, grade 3/4 AE costs were compared between nivolumab + ipilimumab vs. nivolumab + cabozantinib vs. pembrolizumab + lenvatinib using data from the CheckMate 214 (mFU: 26.7 months), CheckMate 9ER (mFU: 23.5 months), and KEYNOTE-581 (mFU: 26.6 months) trials, respectively. Per-patient costs for all-cause and treatment-related grade 3/4 AEs with corresponding any-grade AE rates ≥ 20% were calculated based on the Healthcare Cost and Utilization Project database and inflated to 2020 US dollars. RESULTS: Per-patient all-cause grade 3/4 AE costs for nivolumab + ipilimumab vs. nivolumab + cabozantinib vs. pembrolizumab + axitinib were $2703 vs. $4508 vs. $5772, and treatment-related grade 3/4 AE costs were $741 vs. $2722 vs. $4440 over ~12.8 months of FU. For nivolumab + ipilimumab vs. nivolumab + cabozantinib vs. pembrolizumab + lenvatinib, per-patient all-cause grade 3/4 AE costs were $3120 vs. $5800 vs. $9285, while treatment-related grade 3/4 AE costs were $863 vs. $3162 vs. $5030 over ~26.6 months of FU. CONCLUSION: Patients with aRCC treated with first-line nivolumab-based therapies had lower grade 3/4 all-cause and treatment-related AE costs than pembrolizumab-based therapies, suggesting a more favorable cost-benefit profile.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/pathology , Nivolumab/adverse effects , Axitinib/therapeutic use , Kidney Neoplasms/drug therapy , Kidney Neoplasms/pathology , Ipilimumab/adverse effects , Sunitinib/therapeutic use , Costs and Cost Analysis , Antineoplastic Combined Chemotherapy Protocols/adverse effects
4.
Oncology (Williston Park) ; 37(6): 256-261, 2023 06 12.
Article in English | MEDLINE | ID: mdl-37343207

ABSTRACT

A Hispanic man, aged 42 years, was diagnosed with stage IV metastatic urothelial bladder cancer (MUBC) with nonregional lymphadenopathies and lung, bone, and skin involvement. He received first-line treatment with gemcitabine and cisplatin for 6 cycles, achieving a partial response (PR). Next, he received immunotherapy maintenance with avelumab for 4 months until disease progression. A next-generation sequencing test of paraffin-embedded tumor tissue identified a fibroblast growth factor receptor 3 (FGFR3) S249C missense mutation.


Subject(s)
Carcinoma, Transitional Cell , Urinary Bladder Neoplasms , Male , Humans , Carcinoma, Transitional Cell/drug therapy , Carcinoma, Transitional Cell/pathology , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/pathology , Cisplatin , Pyrazoles
5.
Lancet Oncol ; 23(7): 888-898, 2022 07.
Article in English | MEDLINE | ID: mdl-35688173

ABSTRACT

BACKGROUND: In the primary analysis of CheckMate 9ER, nivolumab plus cabozantinib showed superior progression-free survival, overall survival, and objective response over sunitinib in patients with previously untreated advanced renal cell carcinoma (median follow-up of 18·1 months). Here, we report extended follow-up of overall survival and updated efficacy and safety. METHODS: This open-label, randomised, phase 3 trial was done in 125 hospitals and cancer centres across 18 countries. We included patients aged 18 years or older with previously untreated advanced or metastatic clear-cell renal cell carcinoma, a Karnofsky performance status of 70% or higher, measurable disease according to Response Evaluation Criteria in Solid Tumors version 1.1 assessed by the investigator, any International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic risk category, and available tumour tissue for PD-L1 testing. Patients were randomly assigned (1:1) to nivolumab (240 mg) intravenously every 2 weeks plus cabozantinib (40 mg) orally once daily or sunitinib (50 mg orally) once daily (4 weeks per 6-week cycle). Randomisation, stratified by IMDC risk status, tumour PD-L1 expression, and geographical region, was done by permuted block within each stratum using a block size of four, via an interactive response system. The primary endpoint was progression-free survival by blinded independent central review. Overall survival was a secondary endpoint (reported here as the preplanned final analysis according to the protocol). Efficacy was assessed in all randomly assigned patients; safety was assessed in all patients who received at least one dose of any study drug. This ongoing study, closed to recruitment, is registered with ClinicalTrials.gov, NCT03141177. FINDINGS: Between Sept 11, 2017, and May 14, 2019, 323 patients were randomly assigned to the nivolumab plus cabozantinib group and 328 to the sunitinib group. With an extended follow-up (data cutoff of June 24, 2021; median 32·9 months [IQR 30·4-35·9]), median overall survival was 37·7 months (95% CI 35·5-not estimable) in the nivolumab plus cabozantinib group and 34·3 months (29·0-not estimable) in the sunitinib group (hazard ratio [HR] 0·70 [95% CI 0·55-0·90], p=0·0043) and updated median progression-free survival was 16·6 months (12·8-19·8) versus 8·3 months (7·0-9·7; HR 0·56 [95% CI 0·46-0·68], p<0·0001). Grade 3-4 treatment-related adverse events occurred in 208 (65%) of 320 patients with nivolumab plus cabozantinib versus 172 (54%) of 320 with sunitinib. The most common grade 3-4 treatment-related adverse events were hypertension (40 [13%] of 320 patients in the nivolumab plus cabozantinib group vs 39 [12%] of 320 in the sunitinib group), palmar-plantar erythrodysaesthesia (25 [8%] vs 26 [8%]), and diarrhoea (22 [7%] vs 15 [5%]). Grade 3-4 treatment-related serious adverse events occurred in 70 (22%) of 320 patients in the nivolumab plus cabozantinib group and 31 (10%) of 320 in the cabozantinib group. One additional treatment-related death occurred with sunitinib (sudden death). INTERPRETATION: With extended follow-up and preplanned final overall survival analysis per protocol, nivolumab plus cabozantinib demonstrated improved efficacy versus sunitinib, further supporting the combination in the first-line treatment of advanced renal cell carcinoma. FUNDING: Bristol Myers Squibb and Ono Pharmaceutical.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Carcinoma, Renal Cell , Kidney Neoplasms , Anilides , Antineoplastic Combined Chemotherapy Protocols/adverse effects , B7-H1 Antigen , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/pathology , Follow-Up Studies , Humans , Kidney Neoplasms/drug therapy , Kidney Neoplasms/pathology , Nivolumab/therapeutic use , Pyridines , Sunitinib/therapeutic use
6.
Oncology (Williston Park) ; 36(4): 221-225, 2022 04 06.
Article in English | MEDLINE | ID: mdl-35436063

ABSTRACT

A previously healthy woman, aged 38 years, presented with a 3-month history of fatigue, dyspnea on exertion, significant weight loss, and severe left flank pain; her symptoms restricted any work activities. Laboratory test results were notable for hypercalcemia (corrected serum calcium, 12.8 mg/dL), anemia (9.3 g/dL), and lactate dehydrogenase elevation (>1.5 times the upper limit of normal). A CT scan revealed a 14-cm left renal mass and multiple lung and mediastinal lymph node metastases. A surgical open biopsy was performed; histopathological analysis concluded clear cell renal carcinoma (RCC) with 30% sarcomatoid features. The patient was diagnosed with International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) poor-risk metastatic RCC with sarcomatoid features. She started first-line systemic treatment.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Carcinoma, Renal Cell/pathology , Female , Humans , Immunotherapy , Kidney Neoplasms/pathology , Kidney Neoplasms/surgery , Male , Tomography, X-Ray Computed
7.
J Cancer Educ ; 37(1): 10-15, 2022 02.
Article in English | MEDLINE | ID: mdl-32462498

ABSTRACT

Guidelines recommend discussing fertility preservation with patients with cancer. In Mexico, internists frequently are the primary care provider (PCP) for adults in reproductive age. The knowledge of oncofertility among PCPs in low and middle income countries is poorly known. Internal medicine residents in a tertiary care hospital in Mexico City participated in a survey regarding fertility concepts in cancer patients. Sixty-three residents participated; their median age was 27. Thirty percent reported 0% self-perceived confidence for providing counseling about fertility issues, and 26% reported more than 50% self-perceived confidence. Twenty-eight percent reported not asking patients in reproductive age about satisfied parity/paternity. Eighty-one percent correctly identified patients that should receive fertility counseling, and 68% identified alkylating chemotherapy as having the highest risk of infertility. Fifty-four percent were able to name at least one fertility preservation (FP) strategy for males, whereas 49% were able to name at least one strategy in females. Residents who reported at least 50% self-perceived confidence for providing fertility counseling were more likely to name at least one FP strategy for men (64.7%) versus those who reported less than 50% self-perceived confidence (52.1%), but this result was not statistically significant (p = 0.378). This was similar for FP strategies in women, with 64.7% of more confident residents naming at least one, compared with 43.4% of less confident residents (p = 0.134). Knowledge of FP in patients with cancer is insufficient among internal medicine residents in our institution. Inclusion of oncofertility concepts in the internal medicine program is needed.


Subject(s)
Fertility Preservation , Neoplasms , Adult , Counseling , Female , Humans , Male , Mexico , Neoplasms/psychology , Pregnancy , Surveys and Questionnaires
8.
Oncologist ; 26(2): 157-164, 2021 02.
Article in English | MEDLINE | ID: mdl-33210345

ABSTRACT

BACKGROUND: The early integration of supportive care in oncology improves patient-centered outcomes. However, data are lacking regarding how to achieve this in resource-limited settings. We studied whether patient navigation increased access to multidisciplinary supportive care among Mexican patients with advanced cancer. MATERIALS AND METHODS: This randomized controlled trial was conducted between August 2017 and April 2018 at a public hospital in Mexico City. Patients aged ≥18 years with metastatic tumors ≤6 weeks from diagnosis were randomized (1:1) to a patient navigation intervention or usual care. Patients randomized to patient navigation received personalized supportive care from a navigator and a multidisciplinary team. Patients randomized to usual care obtained supportive care referrals from treating oncologists. The primary outcome was the implementation of supportive care interventions at 12 weeks. Secondary outcomes included advance directive completion, supportive care needs, and quality of life. RESULTS: One hundred thirty-four patients were randomized: 67 to patient navigation and 67 to usual care. Supportive care interventions were provided to 74% of patients in the patient navigation arm versus 24% in usual care (difference 0.50, 95% confidence interval [CI] 0.34-0.62; p < .0001). In the patient navigation arm, 48% of eligible patients completed advance directives, compared with 0% in usual care (p < .0001). At 12 weeks, patients randomized to patient navigation had less moderate/severe pain (10% vs. 33%; difference 0.23, 95% CI 0.07-0.38; p = .006), without differences in quality of life between arms. CONCLUSION: Patient navigation improves access to early supportive care, advance care planning, and pain for patients with advanced cancer in resource-limited settings. IMPLICATIONS FOR PRACTICE: The early implementation of supportive care in oncology is recommended by international guidelines, but this might be difficult to achieve in resource-limited settings. This randomized clinical trial including 134 Mexican patients with advanced cancer demonstrates that a multidisciplinary patient navigation intervention can improve the early access to supportive and palliative care interventions, increase advance care planning, and reduce symptoms compared with usual oncologist-guided care alone. These results demonstrate that patient navigation represents a potentially useful solution to achieve the adequate implementation of supportive and palliative care in resource-limited settings globally.


Subject(s)
Neoplasms , Patient Navigation , Adolescent , Adult , Humans , Mexico , Neoplasms/therapy , Palliative Care , Quality of Life
9.
Oncology (Williston Park) ; 35(5): 272-276, 2021 05 15.
Article in English | MEDLINE | ID: mdl-33998784

ABSTRACT

A man, age 45 years, was diagnosed with intermediate-risk stage IV clear cell renal carcinoma (lung and lymph node metastases). He was prescribed first-line systemic treatment with sunitinib (Sutent) 50 mg per day (each cycle: 4 weeks on, 2 weeks off). Upon day 22 of his second sunitinib cycle, he came to the oncology clinic complaining of difficulty walking due to bilateral sole pain. He described initial tingling sensations, which then became burning and painful, with symmetrical erythema and edema of the soles, without blisters. These turned into painful plaques with yellowish discoloration and hyperkeratosis on pressure-bearing areas. He denied fever or other symptoms. The pain limited his instrumental activities of daily living, but not his self-care activities of daily living. Total body skin examination disclosed hyperkeratotic plaques on the undersurface of the great toes and heels of both feet, predominantly at sites of pressure; no blisters, crusts, ulcers, or fissures were found. No relevant findings were found upon physical examination of his hands, mucosae, and scalp. A diagnosis of grade 2 hand-foot skin reaction (HFSR) was made.


Subject(s)
Antineoplastic Agents/adverse effects , Carcinoma, Renal Cell/drug therapy , Hand-Foot Syndrome/pathology , Kidney Neoplasms/drug therapy , Sunitinib/adverse effects , Adrenal Cortex Hormones/therapeutic use , Antineoplastic Agents/therapeutic use , Hand-Foot Syndrome/drug therapy , Humans , Keratolytic Agents/therapeutic use , Male , Middle Aged , Sunitinib/therapeutic use
10.
J Assist Reprod Genet ; 38(1): 3-15, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33405006

ABSTRACT

PURPOSE: Today, male and female adult and pediatric cancer patients, individuals transitioning between gender identities, and other individuals facing health extending but fertility limiting treatments can look forward to a fertile future. This is, in part, due to the work of members associated with the Oncofertility Consortium. METHODS: The Oncofertility Consortium is an international, interdisciplinary initiative originally designed to explore the urgent unmet need associated with the reproductive future of cancer survivors. As the strategies for fertility management were invented, developed or applied, the individuals for who the program offered hope, similarly expanded. As a community of practice, Consortium participants share information in an open and rapid manner to addresses the complex health care and quality-of-life issues of cancer, transgender and other patients. To ensure that the organization remains contemporary to the needs of the community, the field designed a fully inclusive mechanism for strategic planning and here present the findings of this process. RESULTS: This interprofessional network of medical specialists, scientists, and scholars in the law, medical ethics, religious studies and other disciplines associated with human interventions, explore the relationships between health, disease, survivorship, treatment, gender and reproductive longevity. CONCLUSION: The goals are to continually integrate the best science in the service of the needs of patients and build a community of care that is ready for the challenges of the field in the future.


Subject(s)
Cancer Survivors , Fertility Preservation/trends , Fertility/physiology , Neoplasms/epidemiology , Female , Fertility Preservation/legislation & jurisprudence , Humans , Male , Neoplasms/pathology , Neoplasms/therapy , Quality of Life
11.
Rev Invest Clin ; 73(5): 302-305, 2021.
Article in English | MEDLINE | ID: mdl-34609370

ABSTRACT

Young women with cancer comprise a special population of patients who experience cancer and oncologic care in a unique way. Recent progress in diagnostic and therapeutic approaches has transformed the landscape of clinical oncology practice. This perspective addresses novel therapies, and some of the main challenges that oncologists face when providing care for young patients in the era of next-generation sequencing and tissue-agnostic approaches through the use of targeted therapies for diverse malignancies.


Subject(s)
Medical Oncology , Neoplasms , Adult , Female , Humans , Neoplasms/therapy , Young Adult
12.
Biol Blood Marrow Transplant ; 26(11): 2127-2131, 2020 11.
Article in English | MEDLINE | ID: mdl-32659435

ABSTRACT

Long-term therapy-related reproductive health side effects impact the quality of life of hematopoietic stem cell transplantation (HSCT) survivors. In this study, we evaluated the prevalence of gonadal dysfunction (GD) pre- and post-HSCT, analyzed factors associated with GD, and explored rates of fertility assessment (FA) and fertility preservation (FP) in a resource-limited setting. FA and outcomes of patients age ≤45 years undergoing HSCT between June 2000 and May 2018 were collected retrospectively. We included 213 patients with a median age of 26 years. Pre-HSCT FA was performed in 71.8%, with a GD rate of 17%. The rate of GD was not different between the sexes (females, 19.5% versus males, 16.1%; P = .616) and was only associated with increasing age. The rate of cryopreservation in the cohort was 3.3%. Almost one-half (47.7%) of post-HSCT patients completed FA and evidenced an increase in GD rate to 48.9%. Comparing pre-HSCT and post-HSCT GD rates, women had a significant increase (19.5% versus 81.4%; P < .001), whereas men did not (16.1% versus 20.4%; P = .76). These results were confirmed by a multiple imputation analysis accounting for missing data. Female sex, pre-HSCT cytotoxic therapy, myeloablative conditioning, and germ cell tumor (GCT) diagnosis were associated with post-HSCT GD. Reproductive health preservation can be positively impacted when FA and FP are prioritized at the initial diagnosis in HSCT candidates, particularly in women of older age and men with a diagnosis of GCT. The low FP success observed urges implementation of strategies that favor accessibility and improve quality of life of HSCT survivors in low- and middle-income countries.


Subject(s)
Hematopoietic Stem Cell Transplantation , Quality of Life , Adult , Female , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Male , Middle Aged , Reproductive Health , Retrospective Studies , Survivors
13.
Biol Blood Marrow Transplant ; 26(7): 1350-1354, 2020 07.
Article in English | MEDLINE | ID: mdl-32200119

ABSTRACT

Latent tuberculosis infection (LTBI) affects one-fourth of the world´s population. Hematopoietic stem cell transplantation (HSCT) recipients are at an elevated risk of developing active tuberculosis infection (ATBI). In this retrospective study of donors and HSCT recipients who underwent transplantation between February 2000 and June 2018, our aim was to determine the prevalence of LTBI and ATBI and to describe diagnostic and therapeutic strategies in an HSCT population in an endemic region. The cohort of 409 participants included 125 allogeneic HSCT (allo-HSCT) recipients, 165 autologous HSCT (auto-HSCT) recipients, and 119 HSCT donors. Patients were evaluated pre-HSCT with tuberculin skin test and thoracic imaging. LTBI was diagnosed in 26.2% of the cohort. Cases represented 20% of the auto-HSCT population, 20% of the allo-HSCT population, and 41.2% of the donor population. Pre-HSCT evaluation to rule out ATBI was performed in 62.6% of the cohort; all results were negative. Isoniazid was administered to 73.3% of those with LTBI. Within subgroups, 91.7% of HSCT recipients and 51% of donors received treatment. The median duration of therapy pre-HSCT was 70 days in recipients and 48 days in donors. The incidence of post-HSCT ATBI was 0 at 1-year follow-up. The incidence of LTBI in our population was higher than expected and still might have been underestimated owing to diagnostic test limitations. The absence of incident ATBI suggests that recipients, as opposed to donors, must receive LTBI treatment. Prevention of infectious complications in the HSCT population should be prioritized to improve clinical outcomes. Prospective data from collaborative working groups is needed to determine the best diagnostic and therapeutic approaches in this vulnerable patient population.


Subject(s)
Hematopoietic Stem Cell Transplantation , Latent Tuberculosis , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Latent Tuberculosis/diagnosis , Latent Tuberculosis/epidemiology , Latent Tuberculosis/therapy , Prospective Studies , Retrospective Studies , Transplantation, Homologous
14.
BMC Cancer ; 20(1): 882, 2020 Sep 14.
Article in English | MEDLINE | ID: mdl-32928147

ABSTRACT

BACKGROUND: Cytotoxic chemotherapy can cure advanced germ cell tumors. Nevertheless, cancer treatment may induce cellular senescence and accelerate molecular aging. The aging process implies an increase of cells expressing p16INK4a and changes in lymphocyte subpopulations. Our aim was to study the potential induction of premature immunosenescence in testicular cancer survivors (TCS) exposed to chemotherapy. METHODS: Case-control exploratory study of TCS treated with chemotherapy (≥3 BEP cycles, disease-free ≥3 months) compared with age matched healthy controls. Peripheral blood mononuclear cells were isolated, and lymphocyte subpopulations were analyzed by flow cytometry. CDKN2A/p16INK4a expression in T cells was measured using qPCR. The percentage of lymphocyte subpopulations and the CDKN2A/p16INK4a expression in TCS were compared with the control group using the Wilcoxon signed-rank test. RESULTS: We included 16 cases and 16 controls. The median age was 27 years (minimum 24, maximum 54) and the median time on surveillance was 26.5 months (minimum 3, maximum192). TCS had a lower percentage of total T cells and CD4+ T cells in total lymphocytes. Among the CD4+ T lymphocytes, TCS had less naïve CD4+ and increased memory CD4+ cells. Within the CD8+ T lymphocytes, TCS exhibited a decrease in the percentage of naïve cells and an increase in CD8 + CD45RA + CD57+ cells. TCS also exhibited decreased memory CD19+ B cells compared to the controls. The relative expression of CDKN2A/p16INK4a in T cells was increased in TCS (mean 1.54; 95% CI of the mean: 1.074-2.005; p = 0.048). CONCLUSION: In this exploratory study, TCS showed increased expression of CDKN2A/p16INK4a and a lymphocyte phenotype that has been associated with immunosenescence. Further studies are warranted to define the clinical implications of these alterations in TCS.


Subject(s)
Aging/genetics , Cyclin-Dependent Kinase Inhibitor p16/genetics , Neoplasms, Germ Cell and Embryonal/genetics , Testicular Neoplasms/genetics , Adult , CD4-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/pathology , Cancer Survivors , Female , Humans , Immunosenescence/genetics , Leukocytes, Mononuclear/metabolism , Leukocytes, Mononuclear/pathology , Male , Middle Aged , Neoplasms, Germ Cell and Embryonal/immunology , Neoplasms, Germ Cell and Embryonal/pathology , Testicular Neoplasms/immunology , Testicular Neoplasms/pathology
15.
Oncology (Williston Park) ; 34(4)2020 04 10.
Article in English | MEDLINE | ID: mdl-32293692

ABSTRACT

KEY POINTS • The prognosis for patients with mCRPC has improved over the last few years due to the introduction of novel agents. • The optimal sequence of administering these therapeutic agents remains as a moving target and is not well established. Decisions are usually made according to patients' clinical conditions and disease characteristics, and the safety profile and availability of new drugs. • Recently, cabazitaxel improved outcomes in the third-line setting after docetaxel and an ARTA. Olaparib is an additional option for second- and third-line treatment in those with alterations in BRCA1, BRCA2, and ATM. • Understanding the mechanisms of resistance may provide a rationale for suggesting specific strategies. • A subset of patients may benefit from molecularly targeted therapies, which highlights the importance of genomic testing in the castration-resistant setting. • Immunotherapy may provide benefit to some subsets of patients, such as those with MSI-high tumors. Studies regarding combination therapy with immune checkpoint inhibitors are ongoing.


Subject(s)
Prostatic Neoplasms, Castration-Resistant , Docetaxel/therapeutic use , Humans , Immunotherapy , Male , Molecular Targeted Therapy , Prostatic Neoplasms, Castration-Resistant/pathology , Receptors, Androgen/therapeutic use
16.
Oncology (Williston Park) ; 34(5): 171-174, 2020 May 13.
Article in English | MEDLINE | ID: mdl-32644176

ABSTRACT

A 56-year-old white man with a 74 pack-year smoking history presented with macroscopic hematuria and a significant weight loss of 45 pounds in 6 months. His clinical laboratory tests indicated iron defi ciency anemia and a computed tomography (CT) scan showed a left kidney tumor, mediastinal lymph nodes, and multiple lung metastases. A percutaneous CT-guided kidney biopsy revealed grade 3 clear cell renal carcinoma based on World Health Organization/International Society of Urologic Pathology classifi cation. The patient started first line systemic treatment for intermediate-risk metastatic renal cell carcinoma (mRCC) with combination immunotherapy with nivolumab plus ipilimumab.1 After 10 days of the first cycle, he presented with a pruritic maculopapular rash covering 20% of his body surface.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma, Renal Cell/drug therapy , Kidney Neoplasms/drug therapy , Lung Neoplasms/drug therapy , Anti-Inflammatory Agents/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Renal Cell/immunology , Carcinoma, Renal Cell/pathology , Humans , Immunotherapy/methods , Ipilimumab/administration & dosage , Ipilimumab/adverse effects , Kidney Neoplasms/immunology , Kidney Neoplasms/pathology , Lung Neoplasms/immunology , Lung Neoplasms/secondary , Lymphatic Metastasis , Male , Middle Aged , Nephritis, Interstitial/chemically induced , Nephritis, Interstitial/drug therapy , Nephritis, Interstitial/pathology , Nivolumab/administration & dosage , Nivolumab/adverse effects , Prednisone/administration & dosage , Treatment Outcome
17.
Oncology (Williston Park) ; 34(10): 421-426, 2020 Oct 09.
Article in English | MEDLINE | ID: mdl-33058108

ABSTRACT

A woman, aged 44 years, presented at the general oncology outpatient clinic with bloating, abdominal pain, and significant unintended weight loss. Her past medical history included a bilateral inguinal hernia surgical repair at age 6, and primary amenorrhea since age 15. The patient never underwent additional studies to identify the cause of the primary amenorrhea.


Subject(s)
Androgen-Insensitivity Syndrome/complications , Seminoma/diagnosis , Adult , Diagnosis, Differential , Female , Humans , Male , Neoplasms, Germ Cell and Embryonal/diagnosis
18.
Oncology (Williston Park) ; 34(8): 317-319, 2020 08 12.
Article in English | MEDLINE | ID: mdl-32785928

ABSTRACT

A 78-year-old man had a medical history of hypertension, atrial fibrillation, chronic kidney disease, and metastatic castration-resistant prostate cancer (CRPC). He had progressed to first-line therapy for CRPC with abiraterone plus androgen-deprivation therapy (ADT) and as second-line therapy he was being treated with docetaxel, with biochemical progression in his last prostate specific antigen measurement. He was admitted to the hospital on April 2020, in the middle of the coronavirus disease 2019 (COVID-19) pandemic, because of painful bone lesions and deterioration of renal function.


Subject(s)
Anticoagulants/therapeutic use , Bone Neoplasms/drug therapy , Coronavirus Infections/therapy , Palliative Care , Pneumonia, Viral/therapy , Prostatic Neoplasms, Castration-Resistant/drug therapy , Respiratory Insufficiency/therapy , Aged , Androgen Antagonists/therapeutic use , Androstenes/therapeutic use , Antineoplastic Agents/therapeutic use , Betacoronavirus , Bone Density Conservation Agents/therapeutic use , Bone Neoplasms/complications , Bone Neoplasms/secondary , COVID-19 , Cancer Pain/complications , Cancer Pain/therapy , Coronavirus Infections/complications , Disease Progression , Docetaxel/therapeutic use , Drug Combinations , Eligibility Determination , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Intensive Care Units/supply & distribution , Lopinavir/therapeutic use , Male , Oxygen Inhalation Therapy , Pandemics , Pneumonia, Viral/complications , Prostatic Neoplasms, Castration-Resistant/complications , Prostatic Neoplasms, Castration-Resistant/pathology , Renal Insufficiency , Respiratory Insufficiency/etiology , Reverse Transcriptase Polymerase Chain Reaction , Ritonavir/therapeutic use , SARS-CoV-2 , Severity of Illness Index , Zoledronic Acid/therapeutic use
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