Purpose Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a well-recognized pathologic entity that is challenging and difficult to manage. Recent literature contains several articles, with ...most recommending conservative management. This report describes a treatment modality for advanced cases of BRONJ that involves bone resection and autologous platelet-rich plasma (PRP). Patients and Methods This case series consisted of 25 patients with BRONJ lesions and a history of intravenous bisphosphonate therapy for metastatic bone diseases that did not respond to conservative treatment. All patients were surgically managed by a standardized protocol combining bone resection and PRP. Results Of the 25 patients, 20 (80%) showed complete wound healing during follow-up. Median follow-up was 36 months. Microscopic examination showed actinomyces in 15 specimens. Conclusion BRONJ has been shown to be refractory to conservative management. Treatment of refractory BRONJ with a combination of bone resection and PRP was found to be an effective therapy in most patients and should be considered an alternative treatment modality for management of advanced cases.
We describe two patients with a confirmed diagnosis of high-grade gliomas (grades III/IV), both presenting with O6-methylguanine-DNA methyltransferase (MGMT) methylated and isocitrate dehydrogenase ...(IDH-1) mutated who, after subtotal resection, were submitted to chemoradiation and followed by PCV, a multiple drug regimen (procarbazine, lomustine, and vincristine) associated with cannabidiol (CBD). Both patients presented with satisfactory clinical and imaging responses at periodic evaluations. Immediately after chemoradiation therapy, one of the patients presented with an exacerbated and precocious pseudoprogression (PSD) assessed by magnetic resonance imaging (MRI), which was resolved in a short period. The other patient presented with a marked remission of altered areas compared with the post-operative scans as assessed by MRI. Such aspects are not commonly observed in patients only treated with conventional modalities. This observation might highlight the potential effect of CBD to increase PSD or improve chemoradiation responses that impact survival. Further investigation with more patients and critical molecular analyses should be performed.
Highlights • Induction chemotherapy in non-surgical protocols included a small proportion of patients with oral cavity cancers. • Induction chemotherapy with three drugs (taxane plus PF) followed by ...(chemo)radiotherapy improved overall survival compared to induction chemotherapy with two drugs (PF) followed by (chemo)radiotherapy. • In general, induction chemotherapy followed by chemoradiotherapy compared to chemoradiotherapy upfront has similar clinical outcomes (overall survival). • No overall survival benefit was observed in oral cavity cancer patients treated with induction chemotherapy followed by surgery with or without postoperative radiotherapy compared to surgery upfront with or without postoperative radiotherapy, in randomized, phase 3 clinical trials. • Upcoming studies must focus on identifying biomarker features associated with response to induction chemotherapy and improved survival.
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Objectives: Immune-checkpoint inhibitors (ICI) and targeted-therapies (TT) have become standard options for BRAF-V600 metastatic melanomas (MM). Recently, randomized trials (RCT) addressed the ...efficacy of combined approaches, with conflicting results. We sought to evaluate efficacy and safety of first-line combination ICI and BRAF/MEK inhibitors (triplets) versus BRAF/MEKi (doublets). Methods: We performed a systematic review and metaanalysis of RCT comparing triplet versus doublet published in MEDLINE and EMBASE from 2016-September/2020. We obtained pooled effect estimates through random-effects model assuming p<0.05 as statistically significant. Results: Among 1,784 studies, 3 RCT were selected. Triplets demonstrated progression-free survival (PFS) (HR 0.79 - CI 0.68-0.91, p=0.001) and overall survival (OS) improvement (HR 0.81 - CI 0.67-0.98, p=0.03), with increased rates of grades 3/4 adverse events (AEs), any grade pyrexia, arthralgia, and aminotransferases elevation. AEdiscontinuation rates of all drugs remained similar. Conclusions: Triplets improved PFS and OS with manageable toxicities. These are preliminary results and mature data are expected.
A substantial increase in melanoma incidence has been consistently observed worldwide over the past decades. However, melanoma mortality rates have remained stable or declined over the past years in ...most regions. Given the paucity of melanoma mortality data for different Brazilian regions, we sought to describe melanoma mortality trends in southeastern Brazil and their relationship with demographic variables.
A cross-sectional registry-based analysis was conducted to describe melanoma mortality trends in the state of São Paulo, Brazil, from 1996 to 2016. Demographic information from melanoma-related death records, including sex and age, was collected from the Fundação Sistema Estadual de Análise de Dados database. The annual percentage change (APC) was calculated to identify mortality trends over the period.
An increasing melanoma mortality trend was detected among males, regardless of age (APC, 1.72%;
< .001), and was more pronounced for men ≥ 60 years old (APC, 2.63%;
< .001). Melanoma mortality rates have also increased for patients ≥ 60 years old, regardless of sex (APC, 1.11%;
< .001). A non-statistically significant increase in the overall melanoma mortality rate was observed over the 20-year period analyzed (APC, 0.36%;
= .4).
Our data suggest a stable melanoma mortality over the past two decades for the overall population studied; however, a significant increase in melanoma mortality rates has been demonstrated among males and in the population ≥ 60 years old, emphasizing the need to implement prevention strategies and expand access to effective therapies for this population.
Inflammatory myofibroblastic tumor (IMT) is a rare entity that affects mostly children and young adults. The lungs are the most frequent primary site. When feasible, surgical resection is the ...standard of care and it is associated with long-term survival benefit. Metastatic disease is rare, and central nervous system involvement is very infrequent. There is paucity of data regarding systemic treatment of recurrent or metastatic disease but most IMTs present with ALK rearrangements, becoming potential targets to ALK inhibition. Diagnosis of ALK rearrangements by FISH or RT-PCR is standard and discordant results from immunohistochemistry are rare. Crizotinib is considered the standard therapy in ALK-positive cases. Data supporting the use of other ALK inhibitors are scant and derived only from case reports. We report a case of a patient harboring an ALK-positive by IHC, FISH-negative IMT, that initially responded well to crizotinib but progressed in the CNS, presenting a complete CNS response with second-generation ALK inhibitor alectinib.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The majority of patients diagnosed with glioblastoma develop recurrent disease resulting in poor prognoses. The current study aimed to determine the survival rates of patients diagnosed with ...glioblastoma in Brazil accounting for the influence of age, treatment modalities, public and private practices, and educational level using a population-based national database.
Patients diagnosed with glioblastoma from 1999-2020 were identified from The Fundação Oncocentro de São Paulo database to create a retrospective cohort. Patients were described according to age, education level treatment modalities and medical practice. In a Cox proportional hazards model, controlled for confounding factors for overall survival, the hazard ratio and 95% CI of overall survival in adults was evaluated.
A total of 4,511 patients were included. The median lengths of survival for patients treated in the public and private settings were 8 and 17 months (p<0.001), respectively. Young patients had longer median overall survival (OS: 18 to 40 years, 41 to 60 years, 61 to 65 years, 66 to 70 years and over than 70 years was 22 months, 10 months, 6 months, 5 months, 4 months, respectively (p<0.001). In general, combined treatments were associated with higher median survival compared to monotherapy. The higher educational level, the higher median survival was observed (4 months for illiterate versus 14 months for university degree). In the multivariable analyses, the significant independent predictors for overall survival were practice setting, educational level, age and treatment modalities.
Public practice, older patients, less intensive treatment, and lower educational level were associated with worse survival outcomes in Brazilian glioblastoma patients.
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Solitary fibrous tumor (SFT) is a rare fibroblastic mesenchymal neoplasm with an estimated annual incidence of 0.35 per 100,000 individuals. Doege-Potter syndrome is a paraneoplastic syndrome related ...to solitary fibrous tumor clinically characterized by hypoglycemia, occurring in less than 5% of cases. Herein, we report a case of metastatic SFT associated with recurrent severe hypoglycemia. A 43-year-old male with a noncontributory medical history presented with a painless and progressive growing mass in the right thigh. The histological evaluation rendered the diagnosis of SFT, and tumor resection was performed. One year after the operation, on the oncological follow-up, he was admitted to the emergency unit, manifesting an early-morning seizure associated with a severe hypoglycemia. The laboratory findings of non-islet cell tumor hypoglycemia (NICTH) in the background of a relapsed metastatic solitary fibrous tumor were consistent with the diagnosis of Doege-Potter syndrome. Hepatic embolization associated with oral glucocorticoid was an efficient palliative treatment to control the hypoglycemic crisis and allow hospital discharge.
Introduction: Standard treatment for pediatric patients with localized osteosarcoma includes high-dose methotrexate (HDMTX), and cure rates greater than 60% are observed. However, in adult patients, ...the toxicity profile limits the use of HDMTX and the drug is usually excluded from chemotherapy protocols for this group. We aimed to evaluate the outcomes of adult patients with localized osteosarcoma treated with chemotherapy without methotrexate. Methods: In this retrospective cohort, we evaluated adult patients with high-grade osteosarcoma who received chemotherapy treatment without methotrexate in a reference cancer center from 2007 to 2018. Outcomes analyzed were recurrence-free survival (RFS), overall survival (OS), and prognostic factors associated with overall survival. Results: A total of 48 patients had localized disease and received treatment with chemotherapy without methotrexate. The majority of them received chemotherapy with a combination of cisplatin and doxorubicin (n=42, 87.5%). Median age was 27 years (range 16.8-66.7). With a median follow-up of 29.2 months, median RFS was 29.9 months. Median OS was not reached. 5-year RFS and OS rates were 35.1% (95% CI: 20.3-50.2%) and 71.6% (95% CI: 52.3-84.2%), respectively. Patients who received cumulative doses of doxorubicin ≥375mg/m2 had better OS than those who received lower doses (HR 0.26, 95% CI: 0.07-0.94, p=0.041). Similarly, patients who received ≥6 cycles of neoadjuvant/adjuvant cisplatin tended to have better OS than those who received <6 cycles (HR 0.30, 95% CI: 0.081.09, p=0.069). Nineteen patients received less than 6 cycles of cisplatin and doxorubicin mainly because of grade 3 or 4 toxicities (11), disease progression (6), patient refusal (1), and physician choice (1). Conclusion: In our study, adult patients with localized highgrade osteosarcoma treated with chemotherapy without methotrexate had unfavorable outcomes. The cumulative doxorubicin dose and the number of cisplatin/doxorubicin cycles were associated with improved OS. The investigation of additional treatment strategies is of utmost importance to improve adult patients’ outcomes.
NUT midline carcinoma is a rare and aggressive subset of squamous cell carcinoma, which is characterized by the translocation of nuclear protein in testis gene that is mostly fused with bromodomain ...and extraterminal family proteins. We describe here the first Brazilian case of NUT midline carcinoma with BRD4-NUT fusion detected in a next-generation sequencing panel and we present the clinical evolution of this patient.
A 42-year-old Caucasian man was diagnosed with poorly differentiated squamous cell carcinoma of the left maxillary sinus, with negative in situ hybridization for Epstein-Barr encoding region and human papillomavirus genotyping. He received induction therapy, chemoradiotherapy with weekly systemic chemotherapy, and, concurrently, weekly intra-arterial chemotherapy. New imaging evaluation, 1 month after the end of the last treatment, revealed a good partial response in the primary lesion. However, positron emission tomography-computed tomography showed multiple suspicious lesions in his bones and lungs, which were histologically confirmed. He died exactly 2 months after metastatic disease was diagnosed.
NUT midline carcinoma is usually very aggressive. Currently, there is no standard of care for treatment of NUT midline carcinoma. The definitive diagnosis must be by demonstration of NUTM1 rearrangement. Immunohistochemical staining of greater than 50% of tumor nuclei on formalin-fixed paraffin-embedded tissue using the monoclonal rabbit antibody to NUT (clone C52B1), has a specificity of 100%, and sensitivity of 87% for the diagnosis of NUT midline carcinoma. Our case is the first Brazilian case of NUT midline carcinoma with BRD4-NUT fusion.
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