Background Long-term survival can be achieved in an increasing number of glioma patients after tr... more Background Long-term survival can be achieved in an increasing number of glioma patients after treatment. Therefore, safeguarding these survivors’ quality of life (QoL) is essential. Neurocognitive decline arises in many young patients, placing a heavy burden on the social and economic aspects of the patients’ lives. A lot of debate is currently ongoing regarding the prevalence of neurocognitive impairment and individual predictors of whom is susceptible for such side effect. Material and Methods In this cross-sectional study, 37 WHO grade 2-3 adult glioma survivors, at least one year after multimodal therapy, were tested using a comprehensive neurocognitive test battery covering multiple cognitive domains. Neurocognitive test scores were converted into z-scores using country-specific normative data. Cognitive impairment was defined as a z-score lower or equal to -1.50 for each subtest. Age, time since multimodal therapy, radiotherapy treatment and tumour location were included as p...
BackgroundThe da Vinci Xi system is not Food and Drug Administration approved for transoral robot... more BackgroundThe da Vinci Xi system is not Food and Drug Administration approved for transoral robotic surgery (TORS), resulting in limited data.MethodsThis prospective study evaluates the feasibility, safety, and outcomes of Xi‐TORS in an oncological setting.ResultsSixty‐one patients with head and neck cancer were consecutively included for Xi‐TORS. Adequate exposure and macroscopically complete resection were achieved in 59 patients (success rate = 96.7%). Intraoperative difficulties and complications were encountered in 47.5% and 20.3% of patients, respectively. Postoperative hemorrhage occurred in 11.9%; no treatment‐related deaths were encountered. Two‐year overall survival and disease‐specific survival were 90.5% and 95.6%, respectively. No long‐term (>1 month) tracheotomies were necessary, and only two patients remained tube‐feeding dependent. The functional baseline level was regained at 12 months for the MD Anderson Dysphagia Inventory and at 24 months for the Swallowing qu...
Annals of oncology : official journal of the European Society for Medical Oncology / ESMO, 2014
Afatinib is an oral, irreversible ErbB family blocker that has shown activity in epidermal growth... more Afatinib is an oral, irreversible ErbB family blocker that has shown activity in epidermal growth factor receptor (EGFR)-mutated lung cancer. We hypothesized that the agent would have greater antitumor activity compared with cetuximab in recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients, whose disease has progressed after platinum-containing therapy. An open-label, randomized, phase II trial was conducted in 43 centers; 124 patients were randomized (1 : 1) to either afatinib (50 mg/day) or cetuximab (250 mg/m(2)/week) until disease progression or intolerable adverse events (AEs) (stage I), with optional crossover (stage II). The primary end point was tumor shrinkage before crossover assessed by investigator (IR) and independent central review (ICR). A total of 121 patients were treated (61 afatinib, 60 cetuximab) and 68 crossed over to stage II (32 and 36 respectively). In stage I, mean tumor shrinkage by IR/ICR was 10.4%/16.6% with afatinib and 5....
BACKGROUND In the EORTC 1410/INTELLANCE 2 randomised, phase II study (NCT02343406), with the anti... more BACKGROUND In the EORTC 1410/INTELLANCE 2 randomised, phase II study (NCT02343406), with the antibody-drug conjugate depatuxizumab mafodotin (Depatux-M, ABT-414) in patients with recurrent EGFRamplified glioblastoma, the primary end-point (overall survival) was not met, and the drug had ocular doselimiting toxicity. This study reports results from the prespecified health-related quality of life (HRQoL) and neurological deterioration-free survival (NDFS) exploratory analysis. PATIENTS AND METHODS Patients (n = 260) were randomised 1:1:1 to receive either Depatux-M 1.25 mg/kg or 1.0 mg/kg intravenously every 2 weeks with oral temozolomide (TMZ) 150 mg/m 2 , Depatux-M alone, or TMZ or oral lomustine (CCNU) 110 mg/m 2 (TMZ/CCNU). HRQoL outcomes were recorded using the EORTC core Quality of Life QLQ-C30, and brain cancerspecific QLQ-BN20 questionnaires. Questionnaires were completed at baseline, weeks 8 and 16, and month 6, and changes from baseline to each time point were calculated. NDFS was defined as time to first deterioration in World Health Organisation performance status. RESULTS Compliance with HRQoL was 88.1% at baseline and decreased to 37.9% at month 6. Differences from baseline between Depatux-M arms and TMZ/CCNU in global health/QoL status throughout treatment did not reach clinical relevance (≥10 points). Self-reported visual disorders deteriorated to a clinically relevant extent with Depatux-M arms versus TMZ/CCNU at all timepoints (mean differences range: 24.6-35.1 points). Changes from baseline for other HRQoL scales and NDFS were generally similar between treatment arms. CONCLUSIONS Depatux-M had no impact on HRQoL and NDFS in patients with EGFR-amplified recurrent glioblastoma, except for more visual disorders, an expected side-effect of the study drug. CLINICAL TRIAL REGISTRATION NCT02343406.
Confl ict of interest: This publication is based on the Belgian expert consensus meeting logistic... more Confl ict of interest: This publication is based on the Belgian expert consensus meeting logistically organised by Leo Pharma. Leo Pharma also provided fi nancial support for editorial assistance.
Background: Complete metastasectomy is routinely performed in selected patients with metastatic c... more Background: Complete metastasectomy is routinely performed in selected patients with metastatic clear-cell renal cell carcinoma (ccRCC). Objectives: To assess (1) outcomes after first and repeat metastasectomy, (2) outcomes on targeted therapy in patients who underwent previous metastasectomy and (3) compare outcomes with and without metastasectomy after correction for selection bias. Methods: Metastatic ccRCC patients treated with or without metastasectomy at University Hospitals Leuven were included from prospective databases. We calculated disease-free survival (DFS), time to systemic therapy and cancer-specific survival (CSS) after metastasectomy, and progression-free survival (PFS) and CSS on 1st line sunitinib/pazopanib. We calculated propensity scores to estimate a patient’s likelihood to undergo metastasectomy. Results: We included 113 patients who underwent complete metastasectomy and 139 who did not. (1) Median DFS after complete metastasectomy was 18 mo, time to systemic ...
Quality Indicators (QIs) are important tools to assess the quality and variability of oncological... more Quality Indicators (QIs) are important tools to assess the quality and variability of oncological care. However, their application in neuro-oncology is limited so far. The objective of this study was to develop a set of QIs for glioma, covering process and outcome indicators. A systematic review was conducted to identify both QIs in the field of adult glioma care, and guidelines or recommendations that could be translated into QIs. Also reports from national and international healthcare agencies and scientific associations (“grey literature”) were taken into account. After conversion of these recommendations into QIs, merging with existing QIs found in the literature and rationalization, a two-round Delphi survey was conducted to gain consensus on relevance for the proposed QIs. In total 240 recommendations and 30 QIs were retrieved from the literature. After conversion, merging and rationalization, 147 QIs were evaluated in the Delphi survey and eventually consensus was gained on 47 QIs in the following 7 domains: Diagnosis and Imaging, Surgery, Pathology, Radio/Chemotherapy, Recurrence, Supportive Treatments (Epilepsy, Thromboembolism, Steroid Use and Rehabilitation) and Survival. This study defined a set of 47 QIs for assessing quality of care in adult glioma patients, distributed amongst 7 crucial phases in the patient’s care trajectory. These QIs are readily applicable for use in diverse health care systems, depending on the availability of population-based health care data enabling (inter)national benchmarking.
Objectives: To evaluate the efficacy of systemic treatments in patients with advanced Merkel cell... more Objectives: To evaluate the efficacy of systemic treatments in patients with advanced Merkel cell carcinoma (MCC) prior to the introduction of immune checkpoint modulation. Methods: Fifty-nine patients were treated at the University Hospitals Leuven between 1999 and 2012. Seventeen had advanced disease incurable by radiotherapy and/or surgery, received one or multiple systemic treatments and were included in this retrospective analysis. Results: MCC is a chemotherapy-sensitive tumour with an objective response rate of 63% to first-line chemotherapy. The combination of cisplatin or carboplatin with etoposide was the most frequently used regimen (n=13) with responses seen in 69% of patients. The median progression-free survival after first-line chemotherapy was 8 months. Eight patients received second line chemotherapy with gemcitabine, taxanes or vinca alkaloids with a response rate of 25%. The median overall survival since start of first line chemotherapy was 13 months. Conclusions: A considerable proportion of patients with MCC fails local treatments and requires systemic therapy. Advanced MCC is a chemotherapy-sensitive disease with high response rates. The poor overall survival achieved with chemotherapy supports the need for novel systemic strategies, such as the routine implementation of immunologic treatment approaches. Immune checkpoint modulation is complementary to chemotherapy, and should be further developed as single agent, in sequence or in combination with other biological or cytotoxic therapy.
Purpose of Review The aim of this report is to identify relevant literature reports on salvage tr... more Purpose of Review The aim of this report is to identify relevant literature reports on salvage transoral laser microsurgery (TLM); to consider its oncologic and functional outcomes, as well as reported complications; and to address indications and limitations of salvage TLM. Findings The weighted average of local control after first salvage TLM was 57%. Repeated TLM procedures for second or third recurrences were required in up to 41% of cases, resulting in a weighted average of local control with TLM alone of 67%. The rate of definite laryngeal preservation was 73%. The ultimate local control rate, including cases that required total laryngectomy, was 90%. The overall complication rate after salvage TLM was 14%. Summary Salvage TLM of radiorecurrent laryngeal cancer yields excellent oncologic outcomes. Serious complications are scarce, hospitalization times are short, and functional outcomes in terms of voice and swallowing are favorable when compared to open conservation laryngeal surgery. The key to success is an optimal patient selection.
Background: Recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M-SCCHN) ... more Background: Recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M-SCCHN) overexpresses αvβ5 integrin. Cilengitide selectively inhibits αvβ3 and αvβ5 integrins and is investigated as a treatment strategy.
Advanced salivary gland cancer is a rare disease that comprises different histopathological tumou... more Advanced salivary gland cancer is a rare disease that comprises different histopathological tumour types; correspondingly, data on palliative systemic treatment are scarce. Combination chemotherapy with cyclophosphamide, doxorubicin, and cisplatin (CAP) has been reported to induce a reasonable response rate, although fewer than 100 cases have been described. We conducted a retrospective review of advanced salivary gland cancer patients treated with CAP. Fifteen consecutive patients with recurrent, locally advanced, or metastatic progressive salivary gland cancer treated with CAP were identified over a five-year period. The mean age at start of treatment was 53.5 years, and the male/female ratio was 11/4. The most common histological subtypes were adenoid cystic carcinoma and adenocarcinoma not otherwise specified (NOS), with the parotid gland as the most frequently affected anatomical site. A response rate of 60% was achieved, with one complete and eight partial responses and six st...
Peptide receptor radionuclide therapy (PRRT) consists of the administration of a tumor-targeting ... more Peptide receptor radionuclide therapy (PRRT) consists of the administration of a tumor-targeting radiopharmaceutical into the circulation of a patient. The radiopharmaceutical will bind to a specific peptide receptor leading to tumor-specific binding and retention. The only target that is currently used in clinical practice is the somatostatin receptor (SSTR), which is overexpressed on a range of tumor cells, including neuroendocrine tumors and neural-crest derived tumors. Academia played an important role in the development of PRRT, which has led to heterogeneous literature over the last two decades, as no standard radiopharmaceutical or regimen has been available for a long time. This review provides a summary of the treatment efficacy (e.g., response rates and symptom-relief), impact on patient outcome and toxicity profile of PRRT performed with different generations of SSTR-targeting radiopharmaceuticals, including the landmark randomized-controlled trial NETTER-1. In addition, ...
Glioblastoma (GBM) remains a highly malignant, intrinsically resistant and inevitably recurring b... more Glioblastoma (GBM) remains a highly malignant, intrinsically resistant and inevitably recurring brain tumor with dismal prognosis. The aggressiveness and lack of effective GBM treatments can be attributed to the highly heterogeneous and plastic nature of GBM tumor cells, which easily confer resistance to standard-of-care (SOC) therapy. While tumor progression has also been attributed to interactions with the tumor microenvironment, quantitative data describing these interactions are still largely missing. Here, we used high-dimensional, multiplexed immunohistochemistry to map evolutions in the spatial, single-cell tissue architecture of 120 paired adult GBM tumor samples derived from 60 patients at diagnosis (ND) and upon recurrence (REC) following SOC treatment. We mapped the spatial distribution of a multitude of GBM tumoral subtypes across this multicentric cohort, through which we identified a high level of heterogeneity defined by specific tumoral niches within and across patie...
INTRODUCTIONThe TAVAREC randomized controlled phase II trial examined the efficacy of bevacizumab... more INTRODUCTIONThe TAVAREC randomized controlled phase II trial examined the efficacy of bevacizumab in addition to temozolomide in non-1p19q co-deleted grade II/IIII glioma treated at first recurrence showing contrast enhancement. The trial failed to demonstrate improvement of PFS or OS when bevacizumab was added to temozolomide. Here we present data on the molecular analysis of trial samples.METHODSTumors were reviewed for areas with high tumor percentage. IDH1 and IDH2 mutation status was determined via Sanger sequencing and using immunohistochemistry (n=127/155). Methylation analysis was done using the InfiniumMethylationEpic beadchip (Illumina, n=122/155) from which G-CIMP, 1p/19q and MGMT promoter methylation status (MGMT-STP27) were determined. Trial arms were combined in the prognostic factor analysis. All statistical analyses were performed at 5% significance.RESULTSMutations in IDH1 were found in 97/127 samples and was associated with favorable prognosis. No mutations in IDH2 were identified. 1p/19q codeletion was identified in three tumors. MGMT promoter methylation was present in 89/122 samples (n=33 unmethylated) and was associated with more favorable outcome. Ninety-two tumors were assigned to the prognostically favorable G-CIMP positive subtype (n=30 G-CIMP negative). IDH-mutation status, G-CIMP status and MGMT promoter methylation status were all correlated (P<0.0001). Tumor grade at initial diagnosis was no longer prognostic at tumor recurrence for OS and PFS (also when analysing IDH-mutant tumors only). Multivariate analysis including the molecular and clinical data shows that lesion size, steroids, G-CIMP status and MGMT promoter methylation status are associated with outcome. None of the molecular markers were associated with improved outcome to bevacizumab.CONCLUSIONIn temozolomide-treated recurrent grade II/III non-1p/19q co-deleted tumors, IDH status is prognostic but multivariable analysis indicates CIMP and MGMT status are of more significance. As tumor grade at diagnosis is no longer prognostic in recurrent IDH-mutated, 1p/19q intact tumors, they can be studied together in future clinical trials.
9027 Background: ET-743 (Yondelis) is a marine-derived minor-groove binder which interferes with ... more 9027 Background: ET-743 (Yondelis) is a marine-derived minor-groove binder which interferes with gene activation and nucleotide excision repair, modulates drug-resistance, induces DNA strand breaks, affects the microtubules and blocks the cell cycle in S and G2. The drug is active in a variety of tumors in vitro and in vivo and responses were observed in sarcoma pts in early studies. We performed a retrospective single-center analysis of treatment outcome with ET-743, mainly involving individuals treated in a named-patient compassionate use program. Written informed consent was obtained from all pts. Methods: ET-743 was administered at dosages of 900-1500 μg/m2 as a 24 h iv. infusion q3w. Treatment was continued until progression or excessive toxicity. Results: 89 patients (median age 49 yrs, performance status 0–2) were analyzed. All of them had documented progressive sarcoma at start of treatment. The most common tumor types were leiomyo- (29), lipo- (16) and osteosarcoma (14). Pts had received a median...
Background Long-term survival can be achieved in an increasing number of glioma patients after tr... more Background Long-term survival can be achieved in an increasing number of glioma patients after treatment. Therefore, safeguarding these survivors’ quality of life (QoL) is essential. Neurocognitive decline arises in many young patients, placing a heavy burden on the social and economic aspects of the patients’ lives. A lot of debate is currently ongoing regarding the prevalence of neurocognitive impairment and individual predictors of whom is susceptible for such side effect. Material and Methods In this cross-sectional study, 37 WHO grade 2-3 adult glioma survivors, at least one year after multimodal therapy, were tested using a comprehensive neurocognitive test battery covering multiple cognitive domains. Neurocognitive test scores were converted into z-scores using country-specific normative data. Cognitive impairment was defined as a z-score lower or equal to -1.50 for each subtest. Age, time since multimodal therapy, radiotherapy treatment and tumour location were included as p...
BackgroundThe da Vinci Xi system is not Food and Drug Administration approved for transoral robot... more BackgroundThe da Vinci Xi system is not Food and Drug Administration approved for transoral robotic surgery (TORS), resulting in limited data.MethodsThis prospective study evaluates the feasibility, safety, and outcomes of Xi‐TORS in an oncological setting.ResultsSixty‐one patients with head and neck cancer were consecutively included for Xi‐TORS. Adequate exposure and macroscopically complete resection were achieved in 59 patients (success rate = 96.7%). Intraoperative difficulties and complications were encountered in 47.5% and 20.3% of patients, respectively. Postoperative hemorrhage occurred in 11.9%; no treatment‐related deaths were encountered. Two‐year overall survival and disease‐specific survival were 90.5% and 95.6%, respectively. No long‐term (>1 month) tracheotomies were necessary, and only two patients remained tube‐feeding dependent. The functional baseline level was regained at 12 months for the MD Anderson Dysphagia Inventory and at 24 months for the Swallowing qu...
Annals of oncology : official journal of the European Society for Medical Oncology / ESMO, 2014
Afatinib is an oral, irreversible ErbB family blocker that has shown activity in epidermal growth... more Afatinib is an oral, irreversible ErbB family blocker that has shown activity in epidermal growth factor receptor (EGFR)-mutated lung cancer. We hypothesized that the agent would have greater antitumor activity compared with cetuximab in recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients, whose disease has progressed after platinum-containing therapy. An open-label, randomized, phase II trial was conducted in 43 centers; 124 patients were randomized (1 : 1) to either afatinib (50 mg/day) or cetuximab (250 mg/m(2)/week) until disease progression or intolerable adverse events (AEs) (stage I), with optional crossover (stage II). The primary end point was tumor shrinkage before crossover assessed by investigator (IR) and independent central review (ICR). A total of 121 patients were treated (61 afatinib, 60 cetuximab) and 68 crossed over to stage II (32 and 36 respectively). In stage I, mean tumor shrinkage by IR/ICR was 10.4%/16.6% with afatinib and 5....
BACKGROUND In the EORTC 1410/INTELLANCE 2 randomised, phase II study (NCT02343406), with the anti... more BACKGROUND In the EORTC 1410/INTELLANCE 2 randomised, phase II study (NCT02343406), with the antibody-drug conjugate depatuxizumab mafodotin (Depatux-M, ABT-414) in patients with recurrent EGFRamplified glioblastoma, the primary end-point (overall survival) was not met, and the drug had ocular doselimiting toxicity. This study reports results from the prespecified health-related quality of life (HRQoL) and neurological deterioration-free survival (NDFS) exploratory analysis. PATIENTS AND METHODS Patients (n = 260) were randomised 1:1:1 to receive either Depatux-M 1.25 mg/kg or 1.0 mg/kg intravenously every 2 weeks with oral temozolomide (TMZ) 150 mg/m 2 , Depatux-M alone, or TMZ or oral lomustine (CCNU) 110 mg/m 2 (TMZ/CCNU). HRQoL outcomes were recorded using the EORTC core Quality of Life QLQ-C30, and brain cancerspecific QLQ-BN20 questionnaires. Questionnaires were completed at baseline, weeks 8 and 16, and month 6, and changes from baseline to each time point were calculated. NDFS was defined as time to first deterioration in World Health Organisation performance status. RESULTS Compliance with HRQoL was 88.1% at baseline and decreased to 37.9% at month 6. Differences from baseline between Depatux-M arms and TMZ/CCNU in global health/QoL status throughout treatment did not reach clinical relevance (≥10 points). Self-reported visual disorders deteriorated to a clinically relevant extent with Depatux-M arms versus TMZ/CCNU at all timepoints (mean differences range: 24.6-35.1 points). Changes from baseline for other HRQoL scales and NDFS were generally similar between treatment arms. CONCLUSIONS Depatux-M had no impact on HRQoL and NDFS in patients with EGFR-amplified recurrent glioblastoma, except for more visual disorders, an expected side-effect of the study drug. CLINICAL TRIAL REGISTRATION NCT02343406.
Confl ict of interest: This publication is based on the Belgian expert consensus meeting logistic... more Confl ict of interest: This publication is based on the Belgian expert consensus meeting logistically organised by Leo Pharma. Leo Pharma also provided fi nancial support for editorial assistance.
Background: Complete metastasectomy is routinely performed in selected patients with metastatic c... more Background: Complete metastasectomy is routinely performed in selected patients with metastatic clear-cell renal cell carcinoma (ccRCC). Objectives: To assess (1) outcomes after first and repeat metastasectomy, (2) outcomes on targeted therapy in patients who underwent previous metastasectomy and (3) compare outcomes with and without metastasectomy after correction for selection bias. Methods: Metastatic ccRCC patients treated with or without metastasectomy at University Hospitals Leuven were included from prospective databases. We calculated disease-free survival (DFS), time to systemic therapy and cancer-specific survival (CSS) after metastasectomy, and progression-free survival (PFS) and CSS on 1st line sunitinib/pazopanib. We calculated propensity scores to estimate a patient’s likelihood to undergo metastasectomy. Results: We included 113 patients who underwent complete metastasectomy and 139 who did not. (1) Median DFS after complete metastasectomy was 18 mo, time to systemic ...
Quality Indicators (QIs) are important tools to assess the quality and variability of oncological... more Quality Indicators (QIs) are important tools to assess the quality and variability of oncological care. However, their application in neuro-oncology is limited so far. The objective of this study was to develop a set of QIs for glioma, covering process and outcome indicators. A systematic review was conducted to identify both QIs in the field of adult glioma care, and guidelines or recommendations that could be translated into QIs. Also reports from national and international healthcare agencies and scientific associations (“grey literature”) were taken into account. After conversion of these recommendations into QIs, merging with existing QIs found in the literature and rationalization, a two-round Delphi survey was conducted to gain consensus on relevance for the proposed QIs. In total 240 recommendations and 30 QIs were retrieved from the literature. After conversion, merging and rationalization, 147 QIs were evaluated in the Delphi survey and eventually consensus was gained on 47 QIs in the following 7 domains: Diagnosis and Imaging, Surgery, Pathology, Radio/Chemotherapy, Recurrence, Supportive Treatments (Epilepsy, Thromboembolism, Steroid Use and Rehabilitation) and Survival. This study defined a set of 47 QIs for assessing quality of care in adult glioma patients, distributed amongst 7 crucial phases in the patient’s care trajectory. These QIs are readily applicable for use in diverse health care systems, depending on the availability of population-based health care data enabling (inter)national benchmarking.
Objectives: To evaluate the efficacy of systemic treatments in patients with advanced Merkel cell... more Objectives: To evaluate the efficacy of systemic treatments in patients with advanced Merkel cell carcinoma (MCC) prior to the introduction of immune checkpoint modulation. Methods: Fifty-nine patients were treated at the University Hospitals Leuven between 1999 and 2012. Seventeen had advanced disease incurable by radiotherapy and/or surgery, received one or multiple systemic treatments and were included in this retrospective analysis. Results: MCC is a chemotherapy-sensitive tumour with an objective response rate of 63% to first-line chemotherapy. The combination of cisplatin or carboplatin with etoposide was the most frequently used regimen (n=13) with responses seen in 69% of patients. The median progression-free survival after first-line chemotherapy was 8 months. Eight patients received second line chemotherapy with gemcitabine, taxanes or vinca alkaloids with a response rate of 25%. The median overall survival since start of first line chemotherapy was 13 months. Conclusions: A considerable proportion of patients with MCC fails local treatments and requires systemic therapy. Advanced MCC is a chemotherapy-sensitive disease with high response rates. The poor overall survival achieved with chemotherapy supports the need for novel systemic strategies, such as the routine implementation of immunologic treatment approaches. Immune checkpoint modulation is complementary to chemotherapy, and should be further developed as single agent, in sequence or in combination with other biological or cytotoxic therapy.
Purpose of Review The aim of this report is to identify relevant literature reports on salvage tr... more Purpose of Review The aim of this report is to identify relevant literature reports on salvage transoral laser microsurgery (TLM); to consider its oncologic and functional outcomes, as well as reported complications; and to address indications and limitations of salvage TLM. Findings The weighted average of local control after first salvage TLM was 57%. Repeated TLM procedures for second or third recurrences were required in up to 41% of cases, resulting in a weighted average of local control with TLM alone of 67%. The rate of definite laryngeal preservation was 73%. The ultimate local control rate, including cases that required total laryngectomy, was 90%. The overall complication rate after salvage TLM was 14%. Summary Salvage TLM of radiorecurrent laryngeal cancer yields excellent oncologic outcomes. Serious complications are scarce, hospitalization times are short, and functional outcomes in terms of voice and swallowing are favorable when compared to open conservation laryngeal surgery. The key to success is an optimal patient selection.
Background: Recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M-SCCHN) ... more Background: Recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M-SCCHN) overexpresses αvβ5 integrin. Cilengitide selectively inhibits αvβ3 and αvβ5 integrins and is investigated as a treatment strategy.
Advanced salivary gland cancer is a rare disease that comprises different histopathological tumou... more Advanced salivary gland cancer is a rare disease that comprises different histopathological tumour types; correspondingly, data on palliative systemic treatment are scarce. Combination chemotherapy with cyclophosphamide, doxorubicin, and cisplatin (CAP) has been reported to induce a reasonable response rate, although fewer than 100 cases have been described. We conducted a retrospective review of advanced salivary gland cancer patients treated with CAP. Fifteen consecutive patients with recurrent, locally advanced, or metastatic progressive salivary gland cancer treated with CAP were identified over a five-year period. The mean age at start of treatment was 53.5 years, and the male/female ratio was 11/4. The most common histological subtypes were adenoid cystic carcinoma and adenocarcinoma not otherwise specified (NOS), with the parotid gland as the most frequently affected anatomical site. A response rate of 60% was achieved, with one complete and eight partial responses and six st...
Peptide receptor radionuclide therapy (PRRT) consists of the administration of a tumor-targeting ... more Peptide receptor radionuclide therapy (PRRT) consists of the administration of a tumor-targeting radiopharmaceutical into the circulation of a patient. The radiopharmaceutical will bind to a specific peptide receptor leading to tumor-specific binding and retention. The only target that is currently used in clinical practice is the somatostatin receptor (SSTR), which is overexpressed on a range of tumor cells, including neuroendocrine tumors and neural-crest derived tumors. Academia played an important role in the development of PRRT, which has led to heterogeneous literature over the last two decades, as no standard radiopharmaceutical or regimen has been available for a long time. This review provides a summary of the treatment efficacy (e.g., response rates and symptom-relief), impact on patient outcome and toxicity profile of PRRT performed with different generations of SSTR-targeting radiopharmaceuticals, including the landmark randomized-controlled trial NETTER-1. In addition, ...
Glioblastoma (GBM) remains a highly malignant, intrinsically resistant and inevitably recurring b... more Glioblastoma (GBM) remains a highly malignant, intrinsically resistant and inevitably recurring brain tumor with dismal prognosis. The aggressiveness and lack of effective GBM treatments can be attributed to the highly heterogeneous and plastic nature of GBM tumor cells, which easily confer resistance to standard-of-care (SOC) therapy. While tumor progression has also been attributed to interactions with the tumor microenvironment, quantitative data describing these interactions are still largely missing. Here, we used high-dimensional, multiplexed immunohistochemistry to map evolutions in the spatial, single-cell tissue architecture of 120 paired adult GBM tumor samples derived from 60 patients at diagnosis (ND) and upon recurrence (REC) following SOC treatment. We mapped the spatial distribution of a multitude of GBM tumoral subtypes across this multicentric cohort, through which we identified a high level of heterogeneity defined by specific tumoral niches within and across patie...
INTRODUCTIONThe TAVAREC randomized controlled phase II trial examined the efficacy of bevacizumab... more INTRODUCTIONThe TAVAREC randomized controlled phase II trial examined the efficacy of bevacizumab in addition to temozolomide in non-1p19q co-deleted grade II/IIII glioma treated at first recurrence showing contrast enhancement. The trial failed to demonstrate improvement of PFS or OS when bevacizumab was added to temozolomide. Here we present data on the molecular analysis of trial samples.METHODSTumors were reviewed for areas with high tumor percentage. IDH1 and IDH2 mutation status was determined via Sanger sequencing and using immunohistochemistry (n=127/155). Methylation analysis was done using the InfiniumMethylationEpic beadchip (Illumina, n=122/155) from which G-CIMP, 1p/19q and MGMT promoter methylation status (MGMT-STP27) were determined. Trial arms were combined in the prognostic factor analysis. All statistical analyses were performed at 5% significance.RESULTSMutations in IDH1 were found in 97/127 samples and was associated with favorable prognosis. No mutations in IDH2 were identified. 1p/19q codeletion was identified in three tumors. MGMT promoter methylation was present in 89/122 samples (n=33 unmethylated) and was associated with more favorable outcome. Ninety-two tumors were assigned to the prognostically favorable G-CIMP positive subtype (n=30 G-CIMP negative). IDH-mutation status, G-CIMP status and MGMT promoter methylation status were all correlated (P<0.0001). Tumor grade at initial diagnosis was no longer prognostic at tumor recurrence for OS and PFS (also when analysing IDH-mutant tumors only). Multivariate analysis including the molecular and clinical data shows that lesion size, steroids, G-CIMP status and MGMT promoter methylation status are associated with outcome. None of the molecular markers were associated with improved outcome to bevacizumab.CONCLUSIONIn temozolomide-treated recurrent grade II/III non-1p/19q co-deleted tumors, IDH status is prognostic but multivariable analysis indicates CIMP and MGMT status are of more significance. As tumor grade at diagnosis is no longer prognostic in recurrent IDH-mutated, 1p/19q intact tumors, they can be studied together in future clinical trials.
9027 Background: ET-743 (Yondelis) is a marine-derived minor-groove binder which interferes with ... more 9027 Background: ET-743 (Yondelis) is a marine-derived minor-groove binder which interferes with gene activation and nucleotide excision repair, modulates drug-resistance, induces DNA strand breaks, affects the microtubules and blocks the cell cycle in S and G2. The drug is active in a variety of tumors in vitro and in vivo and responses were observed in sarcoma pts in early studies. We performed a retrospective single-center analysis of treatment outcome with ET-743, mainly involving individuals treated in a named-patient compassionate use program. Written informed consent was obtained from all pts. Methods: ET-743 was administered at dosages of 900-1500 μg/m2 as a 24 h iv. infusion q3w. Treatment was continued until progression or excessive toxicity. Results: 89 patients (median age 49 yrs, performance status 0–2) were analyzed. All of them had documented progressive sarcoma at start of treatment. The most common tumor types were leiomyo- (29), lipo- (16) and osteosarcoma (14). Pts had received a median...
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