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Objective: Patients with a rare cancer (RC) often have a more complex disease trajectory than patients with a common cancer. Research involving both patient groups is needed to identify differences and resemblances. In this study, we aimed to explore and compare experiences, needs and quality of life of patients with rare and common cancer throughout the disease trajectory. Methods: A qualitative focus group study was conducted, including patients with rare and common cancer (n = 25). Participants were purposively selected to reflect heterogeneity of cancer types. A semi‐structured topic list was used. Focus groups (n = 4) were recorded, transcribed verbatim and analysed, using thematic analysis. Results: Three themes were identified emphasizing care inequality between patients with rare and common cancer: (1) The solitary experience: lack of information and support impact the RC patient, (2) Sudden impact, but recognition reduces the common cancer burden, and (3) Absence of psychosocial care requires being empowered as a cancer patient. Conclusions: Patients with RC are faced with enormous challenges due to the high impact of their solitary experience on their quality of life, while patients with common cancer generally experience social support and recognition alleviating their burden. Centralisation of care for patients with RC is needed and tailored psychosocial care should be provided to overcome inequalities. [ABSTRACT FROM AUTHOR]

Cabozantinib is registered in fixed 60 mg dose. However, 46% to 62% of patients in the registration studies needed a dose reduction due to toxicity. Improved clinical efficacy has been observed in renal cell carcinoma patients (RCC) with a cabozantinib exposure greater than 750 μg/L. In our study we explored the cabozantinib exposure in patients with different tumour types. We included RCC patients from routine care and salivary gland carcinoma (SGC) patients from a phase II study with ≥1 measured Cmin at steady‐state. The geometric mean (GM) Cmin at the starting dose, at 40 mg and at best tolerated dose (BTD) were compared between both tumour types. Forty‐seven patients were included. All SGC patients (n = 22) started with 60 mg, while 52% of RCC patients started with 40 mg. GM Cmin at the start dose was 1456 μg/L (95% CI: 1185‐1789) vs 682 μg/L (95% CI: 572‐812) (P <.001) for SGC and RCC patients, respectively. When dose‐normalised to 40 mg, SGC patients had a significantly higher cabozantinib exposure compared to RCC patients (Cmin 971 μg/L [95% CI: 790‐1193] vs 669 μg/L [95% CI: 568‐788]) (P =.005). Dose reductions due to toxicity were needed in 91% and 60% of SGC and RCC patients, respectively. Median BTD was between 20 to 30 mg for SGC and 40 mg for RCC patients. GM Cmin at BTD were comparable between the SGC and the RCC group, 694 μg/L (95% CI: 584‐824) vs 583 μg/L (95% CI: 496‐671) (P =.1). The observed cabozantinib exposure at BTD of approximately 600 μg/L is below the previously proposed target. Surprisingly, a comparable exposure at BTD was reached at different dosages of cabozantinib for SGC patients compared to RCC patients Further research is warranted to identify the optimal exposure and starting dose to balance efficacy and toxicity. What's new? Cabozantinib, a potent tyrosine kinase inhibitor that targets multiple signaling pathways, is approved for use against advanced renal cell carcinoma (RCC). Variations in cabozantinib clearance, however, warrant further investigation. Here, the authors evaluated cabozantinib exposure in RCC patients and in patients with salivary gland cancer (SGC). SGC patients were found to have significantly higher cabozantinib exposure compared to RCC patients following a 40 mg dose. However, the best‐tolerated cabozantinib exposure was equivalent (~600 μg/L) for both tumor types and was substantially below the previously proposed target. The findings offer insight on exposure, dose, and the balance between efficacy and toxicity for cabozantinib. [ABSTRACT FROM AUTHOR]

Background: Timely and efficient diagnostic workup of patients with head and neck cancer (HNC) is challenging. This observational study describes the implementation of an optimized multidisciplinary oncological diagnostic workup for patients with HNC and its impact on diagnostic and treatment intervals, survival, costs, and patient satisfaction.Methods: All patients with newly diagnosed HNC who underwent staging and treatment at the Radboud University Medical Center were included. Conventional workup (CW) in 2009 was compared with the fast-track, multidisciplinary, integrated care program, that is, optimized workup (OW), as implemented in 2014.Results: The study included 486 patients with HNC (218 with CW and 268 with OW). The time-to-treatment interval was significantly lower in the OW cohort than the CW cohort (21 vs 34 days; P < .0001). The 3-year overall survival rate was 12% higher after OW (72% in the CW cohort vs 84% in the OW cohort; P = .002). After correction for confounders, the 3-year risk of death remained significantly lower in the OW cohort (hazard ratio, 1.73; 95% confidence interval, 1.14-2.63; P = .010). Total diagnostic costs were comparable in the 2 cohorts. The general satisfaction score, as measured with the Consumer Quality Index for Oncological Care, was significantly better in a matched OW group than the CW group (9.1 vs 8.5; P = .007).Conclusions: After the implementation of a fast-track, multidisciplinary, integrated care program, the time-to-treatment interval was significantly reduced. Overall survival and patient satisfaction increased significantly, whereas costs did not change. This demonstrates the impact and improved quality of care achieved by efficiently organizing the diagnostic phase of HNC management. [ABSTRACT FROM AUTHOR]

Objective: An increased interval between symptomatic disease and treatment may negatively influence oncologic and/or functional outcomes in head and neck cancer (HNC). This systematic review aims to provide insight into the effects of time to treatment intervals on oncologic and functional outcomes in oral cavity, pharyngeal, and laryngeal cancer.Data Sources: PubMed, EMBASE, and Cochrane library were searched.Review Methods: All studies on delay or time to diagnosis or treatment in oral, pharyngeal, and laryngeal cancer were included. Quality assessment was performed with an adjusted version of the Newcastle-Ottawa scale. Outcomes of interest were tumor volume, stage, recurrence, survival, patient-reported outcome measures (PROMs), toxicity, and functionality after treatment.Results: A total of 51 studies were included. Current literature on the influence of delay in HNC is inconsistent but indicates higher stage and worse survival with longer delay. The effects on PROMs, toxicity, and functional outcome after treatment have not been investigated. The inconsistencies in outcomes were most likely caused by factors such as heterogeneity in study design, differences in the definitions of delay, bias of results, and incomplete adjustment for confounding factors in the included studies.Conclusion: Irrespective of the level of evidence, the unfavorable effects of delay on oncologic, functional, and psychosocial outcomes are undisputed. Timely treatment while maintaining high-quality diagnostic procedures and decision making reflects good clinical practice in our opinion. This review will pose practical and logistic challenges that will have to be overcome. [ABSTRACT FROM AUTHOR]

Background: This study evaluated ototoxicity in locally advanced head and neck cancer patients treated in the CONDOR study with docetaxel/cisplatin/5‐fluorouracil (TPF) followed by conventional radiotherapy with concomitant cisplatin 100 mg/m2 on days 1, 22, and 43 (cis100+RT) versus accelerated radiotherapy with concomitant cisplatin weekly 40 mg/m2 (cis40+ART). Methods: Sixty‐two patients were treated in this study. Audiometry was performed at baseline, during TPF, before start of chemoradiotherapy, and 1, 4, 8, and 12 months after treatment. Results: A complete dataset of audiometric data was available of 12 patients treated with high‐dose cisplatin and of 11 patients treated with intermediate‐dose cisplatin. Patients in the high‐dose group showed significant more hearing loss than in the intermediate group at 4 kHz ([z = 1.98; P = .04] and 8 kHz [z = 2.07; P < .03]). Interindividual variation was high in both groups. Conclusion: After induction TPF, more ototoxicity was observed in chemoradiotherapy with cis100+RT than after chemoradiotherapy with cis40+ART. [ABSTRACT FROM AUTHOR]

Salivary duct carcinoma (SDC) is a subtype of salivary gland cancer with a dismal prognosis and a need for better prognostication and novel treatments. The aim of this national cohort study was to investigate clinical outcome, prognostic factors, androgen receptor (AR) and human epidermal growth factor receptor 2 (HER2) expression. SDC patients diagnosed between 1990 and 2014 were identified by the Nationwide Network and Registry of Histo‐ and Cytopathology in the Netherlands (PALGA). Subsequently, medical records were evaluated and pathological diagnoses reviewed. Data were analyzed for overall survival (OS), disease‐free survival (DFS), distant metastasis‐free survival (DMFS) and prognostic factors. AR was evaluated by immunohistochemistry (IHC), HER2 by IHC and fluorescent in‐situ hybridization. A total of 177 patients were included. The median age was 65 years, 75% were male. At diagnosis, 68% presented with lymph node metastases and 6% with distant metastases. Median OS, DFS and DMFS were 51, 23 and 26 months, respectively. In patients presenting without distant metastases, the absolute number of positive lymph nodes was associated with poor OS and DMFS in a multivariable analysis. AR and HER2 were positive in 161/168 (96%) and 44/153 (29%) tumors, respectively, and were not prognostic factors. SDC has a dismal prognosis with primary lymph node involvement in the majority of patients. The absolute number of lymph node metastases was found to be the only prognostic factor for DMFS and OS. AR expression and—to a lesser extent—HER2 expression hold promise for systemic treatment in the metastatic and eventually adjuvant setting. [ABSTRACT FROM AUTHOR]

Abstract: Background: Salivary duct carcinoma, an aggressive subtype of salivary gland cancer, is mostly androgen receptor‐positive. Only limited data are available on androgen deprivation therapy (ADT). Methods: Patients with advanced androgen receptor‐positive salivary duct carcinoma treated with first‐line ADT were retrospectively evaluated for clinical benefit (ie, partial response [PR] and stable disease, progression‐free survival [PFS] and overall survival [OS]). The OS was compared with patients with advanced salivary duct carcinoma who received best supportive care. Results: Thirty‐four of 35 patients who were ADT‐treated were evaluable: 6 patients had a PR (18%) and 11 had stable disease (32%) leading to a clinical benefit ratio of 50%. The median PFS for the ADT‐treated patients was 4 months and the median duration of clinical benefit was 11 months. The median OS was 17 months versus 5 months in 43 patients receiving best supportive care (P = .02). Conclusion: We recommend ADT in advanced androgen receptor‐positive salivary duct carcinoma given its response and clinical benefit. © 2017 Wiley Periodicals, Inc. Head Neck, 2017 [ABSTRACT FROM AUTHOR]

Background There is an ongoing debate about the value of (neo-)adjuvant chemotherapy in high- and intermediate-grade osteosarcoma of the head and neck. Methods All records of patients older than 16 years diagnosed with osteosarcoma of the head and neck in the Netherlands between 1993 and 2013 were reviewed. Results We identified a total of 77 patients with an osteosarcoma of the head and neck; the 5-year overall survival (OS) was 55%. In 50 patients with surgically resected high- or intermediate-grade osteosarcoma of the head and neck younger than 75 years, univariate and multivariable analysis, adjusting for age and resection margins, showed that patients who had not received chemotherapy had a significantly higher risk of local recurrence (hazard ratio [HR] = 3.78 and 3.66, respectively). Conclusion In patients younger than 75 years of age with surgically resected high- and intermediate-grade osteosarcoma of the head and neck, treatment with (neo-)adjuvant chemotherapy resulted in a significantly smaller risk of local recurrence. Therefore, we suggest (neo-)adjuvant chemotherapy in patients amenable to chemotherapy. © 2016 The Authors Head & Neck Published by Wiley Periodicals, Inc. Head Neck 39: 140-146, 2017 [ABSTRACT FROM AUTHOR]

Background The purpose of this study was to compare the occurrence of cisplatin-induced nephrotoxicity between concomitant chemoradiotherapy with high versus intermediate-dose cisplatin. Methods One hundred forty-four patients with locally advanced head and neck or nasopharyngeal cancer (NPC) were included; 40 patients received cisplatin 100 mg/m2 (high dose) on days 1, 22, and 43, and 104 patients received cisplatin 40 mg/m2 weekly (intermediate dose) during 6 weeks in combination with radiotherapy. Results During treatment with intermediate-dose cisplatin, 6.7% developed an increase of ≥50% serum creatinine versus 60.0% treated with high-dose cisplatin ( p < .05). Nephrotoxicity (all grades) scored by Common Toxicity Criteria for Adverse Events (CTCAE) version 3.0 or CTCAE version 4.03 was 53% and 100% in the high-dose group and 4.8% and 68% in the intermediate-dose group, respectively. Conclusion Significantly less nephrotoxicity occurs during chemoradiotherapy with intermediate-dose cisplatin compared with high-dose cisplatin. The CTCAE version 4.03 seems to be more appropriate in scoring nephrotoxicity than the CTCAE version 3.0. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1575-E1581, 2016 [ABSTRACT FROM AUTHOR]

Background The purpose of this report was to present the results of accelerated radiotherapy (RT) with concomitant weekly cisplatin in head and neck cancer. Methods One hundred six patients received concomitant cisplatin 40 mg/m2 weekly with accelerated RT up to a dose of 68 Gy over 5.5 weeks. Results Ninety-nine percent of the patients received planned RT and 90% received ≥5 cycles of cisplatin. Moist desquamation of skin developed in 45% and confluent mucositis in 82%. Feeding tubes were required in 79% of the patients, and after 12 months in 4%. One patient developed nephrotoxicity. Three-year locoregional control, disease-free survival (DFS), and overall survival (OS) were 72%, 54%, and 61%, respectively. Human papillomavirus (HPV) status was positive on polymerase chain reaction (PCR) and p16 in 11 of 50 patients with oropharyngeal carcinoma. Three-year OS was 81% and 66% in HPV-positive versus HPV-negative patients with oropharyngeal carcinoma. Conclusion Concomitant weekly cisplatin 40 mg/m2 with accelerated RT was well tolerated and treatment compliance was high. © 2015 Wiley Periodicals, Inc. Head Neck 38: E559-E565, 2016 [ABSTRACT FROM AUTHOR]

Background Dysphagia resulting in altered food intake is common among patients with head and neck cancer. This randomized trial investigated the effect of combined individual dietary counseling with individualized swallowing therapy (intervention) compared to individual dietary counseling (control) on normalcy of food intake (NFI). Methods Patients with stage II to IV head and neck cancer treated with postoperative (chemo)radiation were randomly assigned to this study. NFI, dysphagia severity, social eating, and nutritional status were measured at the start of treatment and in weeks 6, 10, 18, and 30. Results One hundred twenty patients, 60 in each group, were recruited. No overall estimated difference was detected for NFI, dysphagia severity, social eating, or nutritional status. At week 10, the intervention group slightly improved dysphagia recovery 0.6 (95% confidence interval [CI] = 0.1-1.1). This difference diminished by week 30. Conclusion Adding individualized swallowing therapy to individual dietary counseling did not improve NFI but slightly accelerate swallowing recovery. © 2015 Wiley Periodicals, Inc. Head Neck 38: E198-E206, 2016 [ABSTRACT FROM AUTHOR]

Background Aggressive fibromatosis (AF) or desmoid tumor of the head and neck region is a rare, usually unresectable, benign soft tissue tumor with locally aggressive behavior. Methods and Results A 31-year-old woman presented with a progressive trismus, a swelling in the retromandibular area, as well as loss of sensibility of the maxillary and mandibular branch of the trigeminal nerve. MRI of the head and neck revealed an infiltrative mass involving the masticator, parapharyngeal, and prevertebral and paravertebral space on the left with intracranial extension through the orbital fissure. After the fifth biopsy, 15 months after presentation, the diagnosis of AF was made. The tumor was unresectable, so intensity-modulated radiotherapy was given with curative intent using a total dose of 60 Gy in 30 fractions of 2 Gy. After 16 months, she showed progressive disease, for which tamoxifen 40 mg twice daily was started with a good response for 2 years. After that, she started with sorafinib, on which she has stable disease now. Conclusion The often long delay in proper diagnosis and the treatment challenges of a desmoid tumor are illustrated in this case. Furthermore, this article reviews the literature concerning AF, especially of the head and neck region. Head Neck, 2013 [ABSTRACT FROM AUTHOR]

BACKGROUND: Recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) is associated with poor survival. Platinum-based chemotherapy is often a first-line treatment. Pemetrexed has shown single-agent activity in SCCHN and in combination with cisplatin for other tumors. This trial examined the efficacy of pemetrexed-cisplatin for SCCHN. METHODS: In a double-blind phase 3 trial, patients with recurrent or metastatic SCCHN and no prior systemic therapy for metastatic disease were randomized to pemetrexed (500 mg/m2) plus cisplatin (75 mg/m2; n = 398) or placebo plus cisplatin (75 mg/m2; n = 397) to assess overall survival (OS) and secondary endpoints. RESULTS: Median OS was 7.3 months in the pemetrexed-cisplatin arm and 6.3 months in the placebo-cisplatin arm (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.75-1.02; P = .082). Median progression-free survival (PFS, months) was similar in both treatment arms (pemetrexed-cisplatin, 3.6; placebo-cisplatin, 2.8; HR, 0.88; 95% CI, 0.76-1.03; P = .166). Among patients with performance status 0 or 1, pemetrexed-cisplatin (n = 347) led to longer OS and PFS than placebo-cisplatin (n = 343; 8.4 vs 6.7 months; HR, 0.83; P = .026; 4.0 vs 3.0 months; HR, 0.84; P = .044, respectively). Among patients with oropharyngeal cancers, pemetrexed-cisplatin (n = 86) resulted in longer OS and PFS than placebo-cisplatin (n = 106; 9.9 vs 6.1 months; HR, 0.59; P = .002; 4.0 vs 3.4 months; HR, 0.73; P = .047, respectively). Pemetrexed-cisplatin toxicity was consistent with studies in other tumors. CONCLUSIONS: Pemetrexed-cisplatin compared with placebo-cisplatin did not significantly improve survival for the intent-to-treat population. However, in a prespecified subgroup analysis, pemetrexed-cisplatin showed OS and PFS advantage for patients with performance status 0 or 1 or oropharyngeal cancers. Cancer 2012. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]

Aim: Sunitinib is an oral tyrosine kinase inhibitor approved for the treatment of renal cell carcinoma (RCC) and gastrointestinal stromal tumor (GIST). Because of the large interpatient pharmacokinetic variability and established exposure-response and exposure-toxicity relationships in clinical trial patients, therapeutic drug monitoring (TDM) seems promising for optimizing sunitinib exposure. We aimed to investigate the relationship between sunitinib exposure and treatment outcome in a real-world patient cohort., Methods: We performed a retrospective observational cohort study in 53 patients with metastatic RCC and 18 patients with metastatic GIST treated with sunitinib and receiving TDM-guided dosing. Time on treatment - as a surrogate for progression-free survival - in patients who achieved adequate sunitinib exposure was compared with patients who did not. Additionaly, the median sunitinib exposure was compared in patients with or without sunitinib-induced toxicity leading to dose reduction., Results: The median time on treatment in patients with RCC who achieved adequate sunitinib exposure (n = 39) was 32 weeks, compared to 15 weeks in patients who did not achieve adequate sunitinib exposure (n = 12) (P = 0.244). In 29 patients (41%) with toxicity leading to dose reduction, sunitinib sum plasma trough concentration (C trough ) until dose reduction was significantly higher compared to patients without toxicity leading to dose reduction (median 60 ng/mL vs 44 ng/mL; P < 0.001) and reduced to comparable levels after dose reduction (44 ng/mL; P = 0.488)., Conclusion: In our real-world patient cohort, patients with sunitinib-induced toxicity requiring dose reduction had significantly higher sunitinib exposure compared to patients without toxicity. The threshold for toxicity, however, was lower compared to that previously described in clinical trials., (© 2020 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Aim: Fixed dose oral tyrosine kinase inhibitors imatinib, sunitinib and pazopanib show a high interpatient variability in plasma exposure. A relationship between plasma exposure and treatment outcome has been established, which supports the rationale for dose optimization of these drugs. The aim of this study was to monitor how many patients reached adequate trough levels after therapeutic drug monitoring-based dose optimization in daily practice., Methods: A cohort study was performed in patients treated with imatinib, sunitinib or pazopanib of whom follow-up drug levels were measured between August 2012 and April 2016. Patients' characteristics were collected by reviewing electronic patient records. Drug levels were measured using high-performance liquid chromatography coupled with tandem mass spectrometry and trough levels were estimated using a predefined algorithm. Dose interventions were proposed based on trough levels., Results: In total, 396 trough levels were determined in 109 patients. Median sample frequency per patient was 3. During the first measurement only 38% of patients showed trough levels within the predefined target ranges despite standard dosing; 52% of the patients showed drug levels below and 10% above the target range. In 35 out of 41 patients (85%) dose interventions led to adequate trough levels. Eventually, 64% of the total cohort reached adequate trough levels., Conclusions: Dose optimization proved an effective tool to reach adequate trough levels in patients treated with imatinib, sunitinib and pazopanib. The percentage of patients with adequate trough levels increased from 38 to 64%. Therapeutic drug monitoring may add to the improvement of efficacy and reduction of toxicity and costs of these treatments., (© 2017 The British Pharmacological Society.)

Aims: In patients with diabetes treated with sunitinib symptomatic hypoglycaemia has been reported. To explore the mechanism of this adverse effect we performed a prospective study to investigate the effect of sunitinib on insulin concentration, insulin clearance and insulin sensitivity., Methods: We studied the early effects of sunitinib on insulin sensitivity and insulin clearance with a hyperinsulinaemic euglycaemic clamp (insulin infusion rate 60 mU m−2 min−1; steady-state 90–120 min) in patients with renal cell carcinoma before and 1 week after the start of sunitinib 50 mg day−1. Insulin sensitivity index (SI) was defined as steady-state glucose disposal divided by the steady-state plasma insulin., Results: Ten patients (one with diabetes, treated with metformin) were included in the study protocol. Steady-state insulin concentrations during the clamp increased after 1 week of sunitinib (from 128.9 ± 9.0 mU l−1 to 170.8 ± 12.8 mU l−1, P < 0.05; 95% CI on difference − 64.3, −19.6). The calculated insulin sensitivity index decreased from 0.22 ± 0.04 before to 0.18 ± 0.02 μmol kg−1 min−1 per mU l−1 insulin (P < 0.05; 95% CI on difference 0.07, 0.08). As the insulin infusion rate was similar for both clamps, the increased steady-state insulin concentration indicates reduced insulin clearance., Conclusion: Sunitinib affects insulin clearance which could possibly lead to overexposure to insulin in patients using insulin or insulin-secretion stimulating agents.