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1.
World Neurosurg ; 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38719077

RESUMO

OBJECTIVE: Treatment of craniopharyngioma typically entails gross total resection (GTR) or subtotal resection with adjuvant radiation (STR-RT). We analyzed outcomes in the adult population undergoing GTR versus STR-RT. METHODS: A total of 115 patients in 5 institutions were enrolled in this retrospective study on adult craniopharyngiomas. Patients with STR received postoperative RT with stereotactic radiosurgery (SRS) or fractionated radiation therapy (FRT) per institutional preference and ability to spare optic structures. RESULTS: Median age was 44 years (19 - 79 years). GTR was achieved in 34 patients and STR-RT in 81 patients with median follow up of 78.9 months (1 - 268 months). For GTR, local control was 90.5% at 2 years, 87.2% at 3 years, and 71.9% at 5 years. For STR-RT local control was 93.6% at 2 years, 90.3% at 3 years, and 88.4% at 5 years. At 5 years following resection there was no difference in local control (p = 0.08). Differences in rates of visual deterioration or panhypopituitarism were not observed between GTR and STR-RT. There was no difference in local control in adamantinomatous and papillary craniopharyngioma regardless of treatment. Additionally, worse local control was found in STR-RT patients that were underdosed with FRT (p = 0.03) or SRS (p = 0.04). CONCLUSIONS: There is good long-term control for adult craniopharyngioma that underwent STR-RT or GTR with no significant difference in local control. First-line treatment for craniopharyngioma should continue to be maximal safe resection followed by RT as needed to balance optimal local control with long term morbidity.

4.
J Immunother Cancer ; 11(8)2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37536941

RESUMO

BACKGROUND: The combination of nivolumab and ipilimumab has been approved for the treatment of multiple solid tumors. This was a phase I study investigating definitive radioimmunotherapy (RIT) with nivolumab and ipilimumab for the treatment of locally advanced (LA) squamous cell carcinoma of the head and neck (SCCHN). METHODS: Patients with newly diagnosed, stage IVA-IVB SCCHN eligible for cisplatin-based chemotherapy received nivolumab (3 mg/kg every 2 weeks for a total of 17 doses) and ipilimumab (1 mg/kg every 6 weeks for a total of 6 doses) starting 2 weeks prior to radiotherapy. The primary endpoint was safety of definitive RIT. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). Exploratory endpoints included the association of baseline programmed death-ligand 1 (PD-L1) expression as well as on-treatment changes in immune bias with treatment outcomes. RESULTS: Twenty-four patients were enrolled. With a median follow-up of 36.1 months, grade 3 or higher treatment-related adverse events were reported in 21 individuals (88%); 5 individuals developed in-field soft tissue ulceration during consolidation immunotherapy, resulting in one fatality. The 3-year PFS and OS rates were 74% (95% CI 58% to 94%) and 96% (95% CI 88% to 100%), respectively. PD-L1 combined positive score (CPS) did not correlate with death or disease progression. Decreases in extracellular vesicle PD-L1 within the concurrent RIT phase were associated with prolonged PFS (p=0.006). Also, interval decreases in circulating interleukin (IL)4, IL9, IL12, and IL17a during concurrent RIT were associated with subsequent ulceration. CONCLUSIONS: Definitive RIT with nivolumab and ipilimumab has sufficient clinical activity to support further development. Early changes in circulating biomarkers appear able to predict treatment outcomes as well as ensuing in-field soft tissue ulceration. TRIAL REGISTRATION NUMBER: NCT03162731.


Assuntos
Neoplasias de Cabeça e Pescoço , Nivolumabe , Humanos , Nivolumabe/farmacologia , Nivolumabe/uso terapêutico , Ipilimumab/farmacologia , Ipilimumab/uso terapêutico , Antígeno B7-H1 , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico
5.
Chin Clin Oncol ; 12(3): 23, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37417289

RESUMO

BACKGROUND: Glioblastoma (GBM) is the most common primary malignant brain tumor in adults. Despite enormous research efforts, GBM remains a deadly disease. The standard-of-care treatment for patients with newly diagnosed with GBM as per the National Cancer Comprehensive Cancer Network (NCCN) is maximal safe surgical resection followed by concurrent chemoradiation and maintenance temozolomide (TMZ) with adjuvant tumor treating fields (TTF). TTF is a non-pharmacological intervention that delivers low-intensity, intermediate frequency alternating electric fields that arrests cell proliferation by disrupting the mitotic spindle. TTF have been shown in a large clinical trial to improve patient outcomes when added to radiation and chemotherapy. The SPARE trail (Scalp-sparing radiation with concurrent temozolomide and tumor treating fields) evaluated adding TTF concomitantly to radiation and chemotherapy. METHODS: This study is an exploratory analysis of the SPARE trial looking at the prognostic significance of common GBM molecular alterations, namely MGMT, EGFR, TP53, PTEN and telomerase reverse transcriptase (TERT), in this cohort of patients treated with concomitant TTF with radiation and chemotherapy. RESULTS: As expected, MGMT promoter methylation was associated with improved overall survival (OS) and progression-free survival (PFS) in this cohort. In addition, TERT promoter mutation was associated with improved OS and PFS in this cohort as well. CONCLUSIONS: Leveraging the molecular characterization of GBM alongside advancing treatments such as chemoradiation with TTF presents a new opportunity to improve precision oncology and outcomes for GBM patients.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Adulto , Humanos , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Temozolomida/farmacologia , Temozolomida/uso terapêutico , Antineoplásicos Alquilantes/uso terapêutico , Dacarbazina/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Medicina de Precisão , Biomarcadores , Metilação de DNA
6.
Pathol Res Pract ; 248: 154689, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37478520

RESUMO

Paraneoplastic syndromes are complex clinical manifestations that occur because of the underlying malignancy in which the malignant cells produce hormones, cytokines, peptides or antibodies that causes symptoms and may affect multiple organ systems. These paraneoplastic conditions may be associated with different solid and hematological malignancies. Multiple Myeloma (MM) accounts for 10-15 % of hematological malignancies and 1-2 % of all malignancies. It is associated with some atypical clinical and laboratory paraneoplastic manifestations. Although there is a low incidence of these paraneoplastic, significant knowledge of these manifestations may assist in making a differential diagnosis in cases of doubt. The clinical presentation may vary and be evident even before or after the diagnosis of malignancy. These include vascular, neurological, dermatological, physiological, and other atypical conditions. Furthermore, these rare paraneoplastic manifestations need more valid, relevant scientific information, as most information about these conditions is derived from case reports. After the literature search, we have reported the paraneoplastic manifestations associated with multiple myeloma, published in the English literature, and the cognate management in this review article. To our knowledge, this is the first review article discussing various paraneoplastic manifestations of multiple myeloma.

8.
J Clin Transl Res ; 9(1): 37-49, 2023 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-36687299

RESUMO

Background and Aim: Diffuse large B-cell lymphoma (DLBCL) has been classified using various parameters, including the site of origin. Studies have reported conflicting outcomes when DLBLC patients were stratified according to the site of origin. This study aimed to investigate the response rate and survival outcomes in nodal versus extranodal DLBCL and compare the results to a region-matched study covering the 1988 - 2005 period. Methods: A single-center retrospective cohort study was conducted on all patients diagnosed with DLBCL and treated in a tertiary care hospital in Pakistan during 2014 - 2019. We calculated the mean and median for continuous variables and frequency and percentages for all categorical variables. Progression-free survival (PFS) and overall survival (OS) were calculated using Kaplan-Meier survival curves. A Cox proportional hazards model was used to determine the hazard ratio (HR) for OS. Results: Of the 118 patients, 49 patients (41.5%) had nodal disease and 69 patients (58.5%) were diagnosed with extranodal DLBCL. The majority of patients in the nodal and extranodal cohorts presented with Stages III and IV disease (73.4% and 62.3%, respectively). A complete response to (immuno) chemotherapy was achieved in 71.4% of nodal DLBCL patients and 65.2% of extranodal DLBCL patients. The 5-year PFS and median PFS in the entire cohort were 0.8% and 17 m, respectively. The PFS and median PFS in the nodal and extranodal DLBCL cohort were 0% and 1.4%, respectively, and 15 m and 19 m, respectively. The 5-year OS and median OS in the entire cohort were 16.1% and 19 m, respectively. The OS and median OS in the nodal and extranodal DLBCL cohort were 8.2% and 21.7%, respectively, and 19 m and 21 m, respectively. Multivariable linear regression revealed that the ABC phenotype (nodal, HR = 1.37, 95% CI = 1.37 - 3.20; extranodal, HR = 1.65, 95% CI = 1.46 - 3.17; GBC as reference) and double and triple hit DLBCL (nodal, HR = 1.29, 95% CI = 1.19 - 2.81; extranodal, HR = 1.87, 95% CI = 1.28 - 2.43; and non-expressors as reference) are independent negative predictors of OS. Conclusions: DLBCL incidence in the Karachi region has remained comparable but patient composition in the extranodal DLBCL cohort has shifted to predominantly advanced stage. Nodal and extranodal DLBCL were associated with similar PFS and OS profiles and first- and second-line treatment responses. Cell of origin and antigen expression status was independent negative predictors of OS, disfavoring the ABC phenotype and lesions with c-MYC and BCL2 and/or BCL6 overexpression. Relevance for Patients: DLBCL is an aggressive type of non-Hodgkin's lymphoma, however; patients respond well to standard systemic chemotherapy. Extranodal type of DLBCL patients tend to have more residual disease after first-line systemic chemotherapy, but physicians should keep in mind that the subsequent line treatment mitigates its negative impact on survival.

10.
Chin Clin Oncol ; 12(6): 69, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38195076

RESUMO

BACKGROUND: Gliomatosis cerebri (GC) is a rare and aggressive form of widely disseminated glioma infiltrating at least 3 lobes of the brain. It is a diffuse pattern of growth seen in glioma rather than a distinct pathological diagnosis based on new Word Health Organization (WHO) classification. Despite this, it is associated with worse prognosis than equally graded gliomas. Tumor treating fields (TTFields) treatment is a more recent advancement in glioma treatment delivered through low energy, intermediate frequency (200 kHz) electromagnetic fields, with multi-modal mechanisms of action. It is Food and Drug Administration (FDA) approved for newly diagnosed and recurrent glioblastoma (GBM). The aim of this case report is to present a durable response of GBM associated GC to concurrent TTFields with chemoradiation. CASE DESCRIPTION: We report a 64-year-old male with left parietal GBM, IDH wild type, WHO grade 4 with extensive GC change. After resection of the enhancing lesion, the patient received concurrent tumor-treating fields (TTFields) with radiation and temozolomide, enrolled in SPARE trial (NCT03477110). The patient had a rapid response in the areas of gliomatosis change demonstrated on the magnetic resonance imaging 1 month post-radiation treatment. The response of GC was durable. His glioma recurred 11 months after surgery with new enhancing lesions, treated with radiosurgery. He had further extensive progression of enhancing lesions 13 months after surgery, and received bevacizumab treatment. The patient ultimately passed away 17 months after surgery. Despite progression of enhancing lesions, the GC changes remained controlled. He also had favorable progression-free survival of 11 months and overall survival of 17 months. CONCLUSIONS: This case serves as an example of how combination TTFields with chemoradiation may elicit a durable response of GC in patients with GBM.


Assuntos
Glioblastoma , Glioma , Estados Unidos , Masculino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Glioma/terapia , Bevacizumab , Quimiorradioterapia
11.
J Neurooncol ; 160(2): 345-350, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36355259

RESUMO

Current standard of care for glioblastoma (GBM) includes concurrent chemoradiation and maintenance temozolomide (TMZ) with Tumor Treating Fields (TTFields). Preclinical studies suggest TTFields and radiation treatment have synergistic effects. We conducted a pilot clinical trial of concurrent chemoradiation with TTFields and report pattern of progression. MATERIALS AND METHODS: This is a single arm pilot study (clinicaltrials.gov Identifier: NCT03477110). Adult patients (age ≥ 18 years) with KPS ≥ 60 with newly diagnosed GBM were eligible. All patients received concurrent scalp-sparing radiation (60 Gy in 30 fractions), standard concurrent TMZ and TTFields. Maintenance therapy included standard TMZ and continuation of TTFields. Radiation treatment was delivered through TTFields arrays. Incidence and location of progression was documented. Distant recurrence was defined as recurrence more than 2 cm from the primary enhancing lesion. RESULTS: Thirty patients were enrolled on the trial. Twenty were male with median age 58 years (19-77 years). Median KPS was 90 (70-100). Median follow-up was 15.2 months (1.7-23.6 months). Ten (33.3%) patients had a methylated promoter status. Twenty-seven patients (90%) had progression, with median PFS of 9.3 months (range 8.5 to 11.6 months). Six patients presented with distant recurrence, with median distance from primary lesion of 5.05 cm (2.26-6.95 cm). One infratentorial progression was noted. CONCLUSIONS: We observed improved local control using concurrent chemoradiation with TTFields for patients with newly diagnosed when compared to historical controls. Further data are needed to validate this finding. TRIAL REGISTRATION: Clinicaltrials.gov Identifier NCT03477110.


Assuntos
Neoplasias Encefálicas , Terapia por Estimulação Elétrica , Glioblastoma , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Terapia Combinada , Glioblastoma/tratamento farmacológico , Projetos Piloto , Temozolomida/uso terapêutico , Adulto Jovem , Idoso
12.
BJUI Compass ; 3(6): 484-493, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36267204

RESUMO

Objectives: To assess cabazitaxel versus docetaxel re-challenge for the treatment of metastatic castrate refractory prostate cancer (CRPC) patients previously treated with docetaxel at inception of primary hormone therapy. Patients and Methods: The CANTATA trial was a prospective, two-arm, open-label, phase II study conducted in eight UK centres. Patients over the age of 18, with histologically proven, metastatic prostate cancer who had been previously treated with up to 6 cycles of docetaxel as part of the STAMPEDE trial (or treated with the same drug outside of the trial at primary diagnosis) and had a performance status (PS) of 0-2, were eligible. Patients who progressed during primary treatment with docetaxel or had received prior systemic chemotherapy were excluded. Cabazitaxel (25 mg/m2) or docetaxel (75 mg/m2) was administered via intravenous infusion every 3 weeks with oral prednisolone (10 mg) for up to 10 cycles, until disease progression, death or unacceptable toxicity. The primary outcome was clinical progression-free survival (PFS) as defined by either date of pain progression, date of a cancer-related skeletal-related event, or date of death from any cause. Analyses were by intention to treat. EudraCT number: 2012-003835-40. Results: Between 7 March 2013 and 4 January 2016, 15 patients with a median age of 70 years (range 54-76) were recruited; seven received cabazitaxel, eight docetaxel. The study was halted due to slow accrual. The median clinical PFS time in the cabazitaxel group was 6.2 months compared with 8.4 for the docetaxel group (95% confidence intervals were not reached due to the small number of patients). A total of 13 serious adverse events were reported. Conclusion: Due to the low number of patients recruited, meaningful comparisons could not be made. However, toxicity was in line with known outcomes for these agents, demonstrating it is feasible and safe to deliver chemotherapy to men relapsing with CRPC after upfront chemotherapy.

13.
Proc Natl Acad Sci U S A ; 119(44): e2208040119, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36279452

RESUMO

Organoid technology has provided unique insights into human organ development, function, and diseases. Patient-derived organoids are increasingly used for drug screening, modeling rare disorders, designing regenerative therapies, and understanding disease pathogenesis. However, the use of Matrigel to grow organoids represents a major challenge in the clinical translation of organoid technology. Matrigel is a poorly defined mixture of extracellular matrix proteins and growth factors extracted from the Engelbreth-Holm-Swarm mouse tumor. The extracellular matrix is a major driver of multiple cellular processes and differs significantly between tissues as well as in healthy and disease states of the same tissue. Therefore, we envisioned that the extracellular matrix derived from a native healthy tissue would be able to support organoid growth akin to organogenesis in vivo. Here, we have developed hydrogels from decellularized human and bovine endometrium. These hydrogels supported the growth of mouse and human endometrial organoids, which was comparable to Matrigel. Organoids grown in endometrial hydrogels were proteomically more similar to the native tissue than those cultured in Matrigel. Proteomic and Raman microspectroscopy analyses showed that the method of decellularization affects the biochemical composition of hydrogels and, subsequently, their ability to support organoid growth. The amount of laminin in hydrogels correlated with the number and shape of organoids. We also demonstrated the utility of endometrial hydrogels in developing solid scaffolds for supporting high-throughput, cell culture-based applications. In summary, endometrial hydrogels overcome a major limitation of organoid technology and greatly expand the applicability of organoids to understand endometrial biology and associated pathologies.


Assuntos
Neoplasias , Organoides , Feminino , Humanos , Bovinos , Animais , Organoides/metabolismo , Hidrogéis/química , Laminina/farmacologia , Laminina/metabolismo , Proteômica , Endométrio , Neoplasias/metabolismo
14.
Front Oncol ; 12: 896246, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35574391

RESUMO

Introduction: Standard-of-care treatment for patients with newly diagnosed glioblastoma (GBM) after surgery or biopsy includes concurrent chemoradiation followed by maintenance temozolomide (TMZ) with tumor treating fields (TTFields). Preclinical studies suggest TTFields and radiotherapy work synergistically. We report the results of our trial evaluating the safety of TTFields used concurrently with chemoradiation. Methods: This is a single-arm pilot study (clinicaltrials.gov Identifier: NCT03477110). Adult patients (age ≥ 18 years) with newly diagnosed glioblastoma and a Karnofsky performance score (KPS) of ≥ 60 were eligible. All patients received concurrent scalp-sparing radiation (60 Gy in 30 fractions) with TMZ (75 mg/m2 daily) and TTFields (200 kHz). Maintenance therapy included TMZ and continuation of TTFields. Scalp-sparing radiation treatment was used to reduce radiation dermatitis. Radiation treatment was delivered through the TTFields arrays. The primary endpoint was safety and toxicity of tri-modality treatment within 30 days of completion of chemoradiation treatment. Results: There were 30 patients enrolled, including 20 (66.7%) men and 10 (33.3%) women, with a median age of 58 years (range 19 to 77 years). Median KPS was 90 (range 70 to 100). A total of 12 (40%) patients received a gross total resection and 18 (60%) patients had a subtotal resection. A total of 12 (40%) patients had multifocal disease at presentation. There were 20 (66.7%) patients who had unmethylated O(6)-methylguanine-DNA-methyltransferase (MGMT) promotor status and 10 (33.3%) patients who had methylated MGMT promoter status. Median follow-up was 15.2 months (range 1.7 to 23.6 months). Skin adverse events were noted in 83.3% of patients, however, these were limited to Grade 1 or 2 events, which resolved spontaneously or with topical medications. The primary end point was met; no TTFields discontinuation occurred during the evaluation period due to high grade scalp toxicity. A total of 27 (90%) patients had progression, with a median progression-free survival (PFS) of 9.3 months (95% confidence interval (CI): 8.5-11.6 months). The 1-year progression-free survival was 23% (95% CI: 12%-45%). The median overall survival (OS) was 15.8 months (95% CI: 12.5 months-infinity). The 1-year overall survival was 66% (95% CI: 51%-86%). Conclusions: Concurrent TTFields with scalp-sparing chemoradiation is a feasible and well-tolerated treatment option with limited toxicity. A phase 3, randomized clinical trial (EF-32, clinicaltrials.gov Identifier: NCT04471844) investigating the clinical benefit of concurrent TTFields with chemoradiation treatment is currently enrolling. Clinical Trial Registration: Clinicaltrials.gov, identifier NCT03477110.

15.
CA Cancer J Clin ; 72(4): 353-359, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35298025

RESUMO

Sexual function is a vital aspect of human health and is recognized as a critical component of cancer survivorship. Understanding and evaluating the impacts of radiotherapy on female sexual function requires precise knowledge of the organs involved in sexual function and the relationship between radiotherapy exposure and sexual tissue function. Although substantial evidence exists describing the impact of radiotherapy on male erectile tissues and related clinical sexual outcomes, there is very little research in this area in females. The lack of biomedical data in female patients makes it difficult to design studies aimed at optimizing sexual function postradiotherapy for female pelvic malignancies. This scoping review identifies and categorizes current research on the impacts of radiotherapy on normal female erectile tissues, including damage to normal functioning, clinical outcomes of radiation-related female erectile tissue damage, and techniques to spare erectile tissues or therapies to treat such damage. An evaluation of the evidence was performed, and a summary of findings was generated according to Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) Extension for Scoping Reviews guidelines. Articles were included in the review that involved normal female erectile tissues and radiotherapy side effects. The results show that little scientific investigation into the impacts of radiotherapy on female erectile tissues has been performed. Collaborative scientific investigations by clinical, basic, and behavioral scientists in oncology and radiotherapy are needed to generate radiobiologic and clinical evidence to advance prospective evaluation, prevention, and mitigation strategies that may improve sexual outcomes in female patients.


Assuntos
Sobreviventes de Câncer , Disfunção Erétil , Lesões por Radiação , Disfunções Sexuais Fisiológicas , Disfunção Erétil/etiologia , Disfunção Erétil/prevenção & controle , Feminino , Humanos , Masculino , Ereção Peniana , Lesões por Radiação/etiologia , Disfunções Sexuais Fisiológicas/etiologia
16.
Eur J Trauma Emerg Surg ; 48(2): 1025-1034, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33547910

RESUMO

PURPOSE: The objective of this systematic review is to compare the safety and efficacy of surgical fixation of rib fractures against non-surgical interventions for the treatment of flail chest in the adult population. METHODS: A search was performed on the 22nd of July 2020 to identify articles comparing surgical fixation versus clinical management for flail chest in adults, with a description of the outcome parameters (resource utility, mortality, adverse effects of the intervention and adverse progression in pulmonary status). Relevant randomised controlled trials were selected, their risk of bias assessed, and the data then extracted and analysed. RESULTS: 157 patients were included from four studies in the analyses, with 79 and 78 patients in the surgical and non-surgical groups, respectively. The pooled effects of all outcomes tended towards favouring surgical intervention. Surgical intervention was associated with lower rates of pneumonia (I2 = 46%, Tau2 = 0.16, p = 0.16), significantly lower rates of tracheostomy (I2 = 76%, Tau2 = 0.67, p = 0.02), and a significantly lower duration of mechanical ventilation (I2 = 88%, Tau2 = 33.7, p < 0.01) in comparison to the non-surgical management methods. CONCLUSION: Our results suggest that surgical intervention reduces the need for tracheostomy, reduces the time spent in the intensive care unit following a traumatic flail chest injury and could reduce the risk of acquiring pneumonia after such an event. There is a need for further well-designed studies with sufficient sample sizes to confirm the results of this study and also detect other possible effects of surgical intervention in the treatment of traumatic flail chest in adults.


Assuntos
Tórax Fundido , Pneumonia , Fraturas das Costelas , Adulto , Tórax Fundido/cirurgia , Fixação Interna de Fraturas/métodos , Humanos , Tempo de Internação , Respiração Artificial/métodos , Fraturas das Costelas/cirurgia
17.
Blood Adv ; 5(20): 4073-4082, 2021 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-34464973

RESUMO

Relapsed or refractory primary central nervous system lymphoma (rrPCNSL) confers a poor prognosis with no accepted standard of care. Very few prospective studies have been conducted in this patient group. This study was a multicenter phase 1/2 study that investigated thiotepa in combination with ifosfamide, etoposide, and rituximab (TIER) for the treatment of PCNSL relapsed or refractory to high-dose methotrexate-based chemotherapy. A 3 + 3 design investigated the recommended phase 2 dose of thiotepa for a single-stage phase 2 cohort by assessing the activity of 2 cycles of TIER against rrPCNSL. The primary outcome was overall response rate. The dose-finding study demonstrated that 50 mg/m2 of thiotepa could be safely delivered within the TIER regimen. No dose-limiting toxicities were encountered in phase 1, and TIER was well-tolerated by the 27 patients treated in phase 2. The most common grade 3 to 4 toxicities were neutropenia (56% of patients) and thrombocytopenia (39%). An overall response was confirmed in 14 patients (52%), which met the prespecified threshold for clinically relevant activity. The median progression-free survival was 3 months (95% confidence interval [CI], 2 to 6 months) and overall survival 5 months (95% CI, 3 to 9 months). Exploratory analyses suggest a greater benefit for thiotepa-naïve patients. Six patients successfully completed autologous stem cell transplantation (ASCT) consolidation, with 4 experiencing durable remissions after a median follow-up of 50 months. The TIER regimen can be delivered safely and is active against rrPCNSL. When it is followed by ASCT, it can provide durable remission and long-term survival. However, for the majority of patients, prognosis remains poor, and novel treatment strategies are urgently needed. This trial was registered at https://www.clinicaltrialsregister.eu/ctr-search/search as EudraCT 2014-000227-24 and ISRCTN 12857473.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfoma não Hodgkin , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Terapia Combinada , Humanos , Linfoma não Hodgkin/tratamento farmacológico , Estudos Prospectivos , Tiotepa/uso terapêutico , Transplante Autólogo
18.
Telemed Rep ; 2(1): 171-178, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34250522

RESUMO

Background: Social determinants of health directly affect cancer survival. Driven by advances in technology and recent demands due to COVID-19, telemedicine has the ability to improve patient access to care, lower health care costs, and increase workflow efficiency. The role of telemedicine in radiation oncology is not established. Materials and Methods: We conducted an IRB-approved pilot trial using a telehealth platform for the first post-radiation visit in patients with any cancer diagnosis. The primary endpoint was feasibility of using telehealth defined by completion of five telehealth visits per month in a single department. Secondary endpoints included the ability to assess patients appropriately, patient and physician satisfaction. Physicians were surveyed again during the pandemic to determine whether viewpoints changed. Results: Between May 27, 2016 and August 1, 2018, 37 patients were enrolled in the Telehealth in Post-operative Radiation Therapy (TelePORT) trial, with 24 evaluable patients who completed their scheduled telehealth visit. On average, 1.4 patients were accrued per month. All patients were satisfied with their care, had enough time with their physician and 85.7% believed the telehealth communication was excellent. All physicians were able to accurately assess the patient's symptoms via telehealth, whereas 82.3% felt they could accurately assess treatment-related toxicity. Physicians assessing skin toxicity from breast radiation were those who did not feel they were able to assess toxicity. Discussion and Conclusions: Both health care providers and patients have identified telemedicine as a suitable platform for radiation oncology visits. Although there are limitations, telemedicine has significant potential for increasing access of cancer care delivery in radiation oncology.

19.
J Radiosurg SBRT ; 7(3): 233-243, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33898087

RESUMO

Our objective is to investigate dosimetric differences between clinically deliverable Gamma Knife® (GK) Icon™ and linac-based FSRT plans on the basis of normal brain dose sparing for large (>14 cm3) recurrent glioblastomas (GBM). Sixteen patients with large, recurrent GBM were treated using re-irradiation via linac-based FSRT, 35 Gy in 10 fractions. For each patient, a new GK FSRT plan was created in Leksell GammaPlan® V11 (LGP). To maintain clinical deliverability, the LGP optimization included a planning goal of treatment time <20 minutes per fraction. Dosimetric comparison of coverage and normal brain dose between the linac and GK treatment plans was performed in MIM. The GK FSRT plans had significantly (p < 0.05) lower mean normal brain dose values (-8.85%), mean values of normal brain V20 (-32.4%) and V12 (-25.9%), and a lower mean V4 (-10.0%). GK FSRT plans have the potential to reduce the risk of radiation-related toxicities.

20.
Adv Radiat Oncol ; 6(2): 100616, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33912732

RESUMO

PURPOSE: Basal cell and cutaneous squamous cell carcinoma are common malignancies (keratinocyte carcinomas [KCs]). Surgical resection is the standard of care. Radiation using high-dose rate brachytherapy (HDR-BT) may serve as a superior alternative where surgical scars may be of cosmetic concern or in elderly patients with significant comorbidity. We aim to describe the clinical and cosmetic outcomes as well as posttreatment radiation toxicities associated with HDR-BT in patients who were treated for KCs of the face. METHODS AND MATERIALS: Patients with KCs treated with HDR-BT from 2015 to 2018 were included in the study. Patient medical records and clinical photos were reviewed at multiple time points: start of treatment, end of treatment, short-term (2 week) follow-up, 3-month follow-up, and if needed at 6 months. Radiation toxicity was graded using the Radiation Therapy Oncology Grading (RTOG) acute toxicity scale. Median (range) toxicity grades at follow-up intervals were calculated. Clinical outcomes including local recurrence were evaluated for all patients. RESULTS: The study included 19 patients and 20 KCs. The median radiation dose was 42 Gy (39-42 Gy) over 6 fractions. The median toxicity at completion of treatment was RTOG grade 2 (85% of patients). At short-term follow-up, 50% of patients (n = 10) improved to RTOG grade 1 (0-2). At 3 months, 70% of patients (n = 14) had RTOG grade 0, and by 6 months, 100% of patients (n = 18) had RTOG grade 0. No RTOG grade 3 or higher skin toxicity was observed. With a median follow-up of 7.2 months (range, 1.3-54.4 months), the local recurrence-free survival was 95%. CONCLUSIONS: We demonstrate that HDR-BT can be used as definitive treatment of KCs of the face with excellent cosmetic outcomes and local control. Acute and subacute skin toxicities were most commonly RTOG grade 2 or less with resolution of patient's skin toxicity by 3 months.

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