Predicting survival in head and neck cancer: External validation and update of the prognostic model OncologIQ in 2189 patients

xlomafota13 shared this article with you from Inoreader Predicting survival in head and neck cancer: External validation and update of the prognostic model OncologIQ in 2189 patients Via Head & Neck Abstract Background Disclosing prognostic information is necessary to enable patients to make well‐informed treatment decisions. OncologIQ is a prognostic model that predicts the overall survival (OS) probability in patients with head and neck squamous cell carcinoma (HNSCC). We aimed to externally validate and update the model with new prognostic factors and translate it to a clinically useful tool. Methods A consecutive retrospective sample of 2189 patients eligible for curative treatment of a primary HNSCC were selected. Discriminative performance was determined using the C‐statistic. Results External validation showed systematic underestimation of OS in the new population, and reasonable discrimination (C‐statistic 0.67). Adding smoking, pack years, BMI, weight loss, WHO performance, socioeconomic status, and p16 positivity to the recalibrated multivariable model, improved the internally validated C‐statistic to 0.71. The model showed minor optimism and was translated in an online tool (www.oncologiq.nl). Conclusions The updated model enables personalized patient counseling during treatment decision consultations. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Maxillectomy defects: Virtually comparing fibular and scapular free flap reconstructions

xlomafota13 shared this article with you from Inoreader Maxillectomy defects: Virtually comparing fibular and scapular free flap reconstructions Via Head & Neck Abstract Background This study virtually compares patient‐specific fibular and scapular reconstructions for maxillectomies. Methods Nine maxillectomy defects were created on 10 maxillas and virtually reconstructed with patient‐specific fibulas and scapulas. Reconstructions were compared for restoring midface cephalometrics, dental implantability, and pedicle length. Results Of 90 maxillectomy defects, the vertically oriented scapula provided improved orbital floor and maxillary height reconstructions (p < 0.001), albeit at the cost of dental implantability compared to the fibula (p < 0.001). In two defects crossing the midline, the fibula, allowing for more osteotomies, provided improved maxillary projection. In the remaining three defects crossing the midline, the horizontally oriented scapula was comparable to the fibula. Fibular and scapular reconstructions were amenable for dental implantation and had similar pedicle lengths, although favoring scapula in extensive defects. Conclusion Fibular and scapular reconstructions of maxillectomy defects provide unique strengths. This virtual analysis can guide a goal‐oriented reconstruction based on defect type and patient‐specific goals. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Impact of anatomic site of distant metastasis on survival in salivary gland cancers

xlomafota13 shared this article with you from Inoreader Impact of anatomic site of distant metastasis on survival in salivary gland cancers Via Head & Neck Abstract Background As exemplified in patients with adenoid cystic carcinoma (ACC), metastatic salivary gland cancers display heterogenous behavior. Although anatomic site of metastasis has been suggested to be prognostic for survival in this population, this is not adequately characterized in the current literature. Methods Using the National Cancer Database (NCDB), patients with newly diagnosed metastatic salivary gland cancers with distant metastasis to a single organ were identified. Results Eight hundred and fifty‐eight patients (n = 284 bone‐only, n = 322 lung‐only, n = 252 other‐site‐only) were identified. Anatomic site of distant metastasis was not associated with survival in the cohort as a whole; however, on pre‐planned subgroup analysis, lung‐only metastasis, relative to bone‐only metastasis, was the only factor associated with improved survival in patients with ACC (HR: 0.52, 95%CI: 0.30–0.93, p = 0.029). Conclusions Anatomic site of metastasis is strongly associated with survival in patients with metastatic ACC and should be considered in future studies aiming to optimize therapy in this population. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Sarcoid-like reaction in a BRAF V600E-mutated metastatic melanoma patient during treatment with BRAF/MEK-targeted therapy

xlomafota13 shared this article with you from Inoreader Sarcoid-like reaction in a BRAF V600E-mutated metastatic melanoma patient during treatment with BRAF/MEK-targeted therapy Via Melanoma Research - Current Issue Treatment with combined BRAF and MEK inhibition is widely accepted as a first-line treatment option for patients with advanced BRAF V600E mutant melanoma. It is generally well-tolerated and has limited side-effects. However, we report a case of a sarcoid-like syndrome induced by treatment with dabrafenib/trametinib (D/T) in a patient with stage IV-M1d melanoma. Sarcoid-like syndrome is a known side-effect of immune checkpoint-inhibition therapy but has only rarely been described in BRAF/MEK inhibition. However, recognizing this side-effect is important because of potential misinterpretation as progressive disease and influence on treatment. We describe a 48-year-old female patient who initially presented with solitary brain metastasis and diffuse lung lesions. She was treated with D/T to which she had an initial response in all lesions. One year later, new hilar and mediastinal lymphadenopathies were detected. Imaging was suggestive of the sarcoid-like syndrome. An endoscopic biopsy of the enlarged lymph node showed no melanoma cells. Treatment was continued. Three months later, the patient experienced a drop in hemoglobin, which prompted further investigations into possible occult intestinal metastasis. Video capsule examination revealed a metastatic lesion in the small intestine. A treatment switch to the combination of checkpoint inhibitors nivolumab and ipilimumab successfully treated both lung and small intestine lesions. After the third dose of this combination therapy, she developed an immune-related pneumonitis. Treatment with corticosteroids resolved the pneumonitis and decr eased metabolism in the sarcoid-like syndrome. The treatment was not restarted afterward. She remains free of the disease up to today, 2.5 years after diagnosis. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Response to immune checkpoint inhibitor rechallenge after high-grade immune related adverse events in patients with advanced melanoma

xlomafota13 shared this article with you from Inoreader Response to immune checkpoint inhibitor rechallenge after high-grade immune related adverse events in patients with advanced melanoma Via Melanoma Research - Current Issue Twenty to sixty percent of patients receiving immune checkpoint inhibitors (ICIs) experience high-grade immune-related adverse events (irAEs) which may prevent the continuation of treatment. Limited clinical evidence is available to guide treatment for these patients. Patients with stage IV or unresectable stage III melanoma at NYU Langone Health were reviewed from 1 January 2014 to 1 July 2019. Patients with first-line ICI systemic therapy, a high-grade irAE and a rechallenge with ICI therapy were included. Postrechallenge irAE recurrence, response rate, overall survival (OS) and progression-free survival (PFS) were evaluated. Postrechallenge irAEs recurred in 71.9% (n = 23/32) of patients at a median of 5.1 weeks from rechallenge, with 46.9% (15/32) recurring as high-grade events. Clinical response was achieved in 46.9% (15/32) of patients, including 40.6% (13/32) with a complete response and 6.3% (2/32) with partial response. Median OS from first ICI initiation was 85.4 weeks (45.7–140.7; 25th—75th percentile) and median PFS was 42.9 weeks (29.2–114.2; 25th–75th percentile). Patients with a shorter time to initial irAE and shorter time to postrechallenge irAE were at greater risk for disease progression [hazard ratio 7.80; 95% confidence interval (CI), 1.91–32.83; P = 0.004; hazard ratio 7.45, 95% CI, 1.57–35.35; P = 0.012). Those with greater duration to rechallenge (>10 weeks) were at lower risk for disease progression (hazard ratio 0.15, 0.03–0.68; P = 0.015). ICI rechallenge can be considered in patients with advanced melanoma, as the risk-ben efit profile appears favorable. Treatment toxicity should be appropriately managed, as longer durations to rechallenge may lower the risk of disease progression. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Melanoma-specific expression of the tumor suppressor proteins p16 and PTEN is a favorable prognostic factor in established melanoma brain metastases

xlomafota13 shared this article with you from Inoreader Melanoma-specific expression of the tumor suppressor proteins p16 and PTEN is a favorable prognostic factor in established melanoma brain metastases Via Melanoma Research - Current Issue PTEN and p16 frequently undergo (epi)genetic aberrations in melanoma resulting in decreased, or absent, protein levels. We investigated the prognostic significance of these tumor suppressor genes in melanoma brain metastases (MBMs). Immunohistochemical analysis was performed on archived tissue sections from craniotomies. Expression of PTEN and p16 was semiquantitatively scored (0–3 scale) in melanoma cells, glia, TILs, and endothelial cells of tumor-associated vessels and was compared among the different brain tumor cell compartments. Overall survival (OS) analysis was performed according to PTEN and p16 prot ein expression in melanoma cells. 58 patients (median age 56, 37 male) underwent craniotomy for MBMs before February 2014. The OS of patients with decreased, or absent, protein expression (0, 1+) of PTEN and p16 in melanoma cells was significantly shorter compared to that of patients with high (2+, 3+) expression (median OS 2.40 vs. 10.75 months and 4.1 vs. 8.1 months, respectively; Gehan-Breslow-Wilcoxon test P = 0.026 and P = 0.037, respectively). PTEN and p16 protein expression were significantly lower in TILs compared to melanoma cells (Mann–Whitney test P = 0.023 and P  View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Treatment of in-transit melanoma metastases using intralesional PV-10

xlomafota13 shared this article with you from Inoreader Treatment of in-transit melanoma metastases using intralesional PV-10 Via Melanoma Research - Current Issue Melanoma in-transit metastases (ITMs) can sometimes be difficult to manage by surgical excision due to their number, size or location. Treatment by intralesional injection of PV-10, a 10% solution of rose bengal, has been reported to be a simple, safe and effective alternative, but more outcome data are required to confirm its value in the management of ITMs. Two hundred and twenty-six melanoma ITMs in 48 patients were treated with intralesional PV-10 supplied under a special-access scheme. By 8 weeks a complete response in all injected ITMs was achieved in 22 patients (46%) and a partial response in 19 patients (40%). Of 19 patients who had uninjected metastases, 3 (16%) had a response in these. The most common adverse event was transient localised pain in injected tumours. New ITMs developed in 25 patients within 8 weeks, and later in another 8 patients. Repeat injection cycles were given to 21 patients: 13 of these received repeat injection into partially responding or nonresponding tumours, 5 had new ITMs, as well as partially-responding lesions injected, and 3 received injection into new ITMs only. Twenty-two patients received subsequent systemic therapy. At 1 year 37 of the 48 patients were alive, 28 with melanoma, and at 2 years 27 were alive, and 19 with melanoma. Injection of PV-10 was simple and safe and resulted in tumour involution in most patients and sometimes in noninjected tumours. However, many patients developed new lesions; these were treated by further PV-10 injections or with alternative therapies. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

A novel C-terminal Hsp90 inhibitor KU758 synergizes efficacy in combination with BRAF or MEK inhibitors and targets drug-resistant pathways in BRAF-mutant melanomas

xlomafota13 shared this article with you from Inoreader A novel C-terminal Hsp90 inhibitor KU758 synergizes efficacy in combination with BRAF or MEK inhibitors and targets drug-resistant pathways in BRAF-mutant melanomas Via Melanoma Research - Current Issue Melanoma remains the most aggressive and fatal form of skin cancer, despite several FDA-approved targeted chemotherapies and immunotherapies for use in advanced disease. Of the 100 350 new patients diagnosed with melanoma in 2020 in the US, more than half will develop metastatic disease leading to a 5-year survival rate View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Impact of staging on survival outcomes: a nationwide real-world cohort study of metastatic uveal melanoma

xlomafota13 shared this article with you from Inoreader Impact of staging on survival outcomes: a nationwide real-world cohort study of metastatic uveal melanoma Via Melanoma Research - Current Issue No data exist regarding whether any first-line treatment for metastatic uveal melanoma provides overall survival (OS) benefit, if staged and compared to best supportive care (BSC). We analyzed OS in a nationwide, consecutive cohort diagnosed with metastatic uveal melanoma between January 1999 and December 2016. The Helsinki University Hospital Working Formulation was used to assign patients to stage IVa, IVb and IVc, corresponding to predicted median OS ≥12, View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Extreme elevation of acute phase reactants and shock secondary to dabrafenib–trametinib

xlomafota13 shared this article with you from Inoreader Extreme elevation of acute phase reactants and shock secondary to dabrafenib–trametinib Via Melanoma Research - Current Issue The emerging role of BRAF and MEK tyrosine-kinase inhibitors has shown new opportunities of treatment for patients with advanced melanoma and BRAF mutations. Its use is associated with some toxicities, as pyrexia, that clinicians may not be familiarized with. We present the case of a patient diagnosed with stage IV melanoma BRAF Val600E mutated who was started on dabrafenib and trametinib and developed three severe episodes of fever, hypotension and acute phase reactants elevation during the first 3 months of therapy, in the absence of microbiological demonstration of infection. The episodes were initia lly managed as a septic shock with broad-spectrum antibiotics and vasoactive drugs, while treatment with dabrafenib and trametinib was withheld. After two subsequent dose reduction of dabrafenib, the patient did not experience new episodes of fever. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

BRAF inhibitor treatment is feasible in the oldest-old advanced melanoma patients

xlomafota13 shared this article with you from Inoreader BRAF inhibitor treatment is feasible in the oldest-old advanced melanoma patients Via Melanoma Research - Current Issue Although new compounds have improved the treatment landscape of metastatic melanoma, very limited data exist on the efficacy and safety of treating older patients with novel agents. Here, we provide results of BRAF (BRAFi) ± MEK (MEKi) inhibitor treatment in patients over 75 years (oldest-old patients) with metastatic melanoma. Between 2011 and 2020, 34 consecutive patients with metastatic melanoma over 75 years of age (range 75–89) were treated with BRAFi ± MEKi at the Comprehensive Cancer Center of Helsinki University Hospital. Data on clinical and histopathological features, toxicity, respo nse rate (RR), progression-free survival (PFS) and overall survival (OS) were collected. Patients were treated with BRAFi (n = 22) or BRAFi in combination with MEK inhibitor (MEKi) (n = 12). Grade 1–2 adverse events occurred in 68% of the patients, 32% had grade 3 adverse effects, dose reductions were made for 41% of patients and 29% terminated treatment due to toxicity. Overall, the RR was 62%. Complete responses were achieved in 27% of the patients, and 35% had partial responses. The median PFS was 8 months (range 0–57), and the median OS was 15 months (range 0–71). Tailored BRAFi ± MEKi treatment for older patients is feasible. Adverse effects occur frequently but are manageable by dose adjustment. The occurrence of toxicity of monotherapy was similar to that of combination therapy. The RR and median OS from our retrospective study are comparable with those reported in clinical trials and combination therapy produced somewhat more and longer-lasting respons es. Hence, it seems that older patients may benefit from BRAFi treatment. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

A case of hyperprolactinaemia in a patient with metastatic melanoma

xlomafota13 shared this article with you from Inoreader A case of hyperprolactinaemia in a patient with metastatic melanoma Via Melanoma Research - Current Issue Ectopic prolactin production from a malignancy is infrequently reported. We report here a 60-year-old gentleman who presented with hyperprolactinaemia (9100 mIU/L) causing expressible galactorrhoea, decreased libido and fatigue thought to be due to ectopic prolactin secretion from a metastatic melanoma. Upon initiation of pembrolizumab, the patient's symptoms resolved and he became normoprolactinaemic. This corresponded with a partial response on radiological imaging. Although the core biopsy of the metastatic melanoma did not exhibit immunostaining for prolactin, we believe that only a subset of the tumour cells possesses prolactin-secreting capacity. This case illustrates the need to consider ectopic prolactin production for a solid malignant tumour as a rare cause of hyperprolactinaemia in patients with a normal pituitary MRI, in the absence of other causes. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.