Causes of death in patients with locally advanced head and neck cancer treated with radiotherapy and systemic therapy.

BACKGROUND: To investigate the incidence of non-cancer mortalities and prognostic factors associated with competitive causes of death in a homogeneous cohort of patients with locally advanced head and neck cancer treated with radiotherapy and systemic treatment. METHODS: This study included 284 patients with locally advanced head and neck cancer treated with radiotherapy and systemic treatment between 2005 and 2017. The cumulative incidence of death associated with tumour, second tumours, treatment, side effects and comorbidity was calculated. A Fine and Gray regression model was used to investigate factors associated with cancer and competitive mortality. RESULTS: The cumulative incidence of tumoral death at 5 and 10 years were 35 and 47% respectively, whereas the cumulative incidence of competitive mortality were 10 and 12% respectively. In the multivariate analysis, age and comorbidity were independent factors for non-cancer mortality. Patients with a high risk of non-cancer mortality presented a cumulative incidence of 17.3% at 5 years and 18.4% at 10 years. CONCLUSIONS: This study demonstrated a high incidence of competing mortality in older patients with comorbidities. Non-cancer deaths should be considered when selecting patients for combination therapies and in the study design ofclinical trials.

Bevacizumab for recurrent, persistent or advanced cervical cancer: reproducibility of GOG 240 study results in 'real world' patients

Purpose: Bevacizumab is the only therapeutic target approved for patients with persistent, recurrent or advanced cervical cancer from a phase III study that combined with chemotherapy; it proves a significant increase in overall survival. To retrospectively assess the efficacy and safety of bevacizumab as the first-line treatment in patients from usual clinical practice with recurrent/persistent or advanced cervical cancer. Patients and methods: Treatment consisted of cisplatin 50 mg/m2 or carboplatin AUC 5 plus paclitaxel 175 mg/m2 for 6-8 cycles and bevacizumab 15 mg/kg every 3 weeks up to progression or unacceptable toxicity. The endpoints were progression-free survival (PFS), overall survival (OS), response rates (RR) and toxicity. Results: Twenty-seven patients were included from January 2014 to June 2017, with a median follow-up 10, 1 months. Eleven percent had recurrent/persistent disease and 89% had metastatic disease at diagnosis. The prior exposition to platinum was 70%. The median PFS and OS were 9, 6 and 21, 5 months, respectively. There was an increase of fistula formation (22%). All of them had pelvic and peritoneal disease at the beginning of treatment and previous treatment with chemoradiotherapy; non-incidence differences were found according to the type of platinum agent used. There were two treatment-related deaths, one from intestinal perforation and another from severe sepsis. Conclusion: Finally, although our study does have certain limitations, we believe that it can provide useful information and encouraging evidence that the routine use of bevacizumab as part of first-line treatment of patients with advanced cervical cancer may be associated with outcomes comparable with those obtained in GOG240 study

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Grado de acuerdo entre la acelerometría y el Cuestionario Internacional de Actividad Física en pacientes supervivientes de cáncer de mama / Level of agreement between accelerometry and the International Physical Activity Questionnaire in breast cancer survivors

Objetivo primario: Analizar el grado de acuerdo entre la medida autoinformada provista por el International Physical Activity Questionnaire (IPAQ) y la medida objetiva aportada por los acelerómetros (ActiGraph) en mujeres supervivientes a un cáncer de mama. Objetivo secundario: Evaluar la percepción de sensación de fatiga de estas pacientes, así como su estado de ánimo y la fuerza prensil. También quisimos comprobar la relación entre el soporte social y la práctica de actividad física. Material y método: Las 10 participantes llevaron un acelerómetro 9 días y a su retirada completaron los cuestionarios IPAQ, PIPER, POMS, uno de valoración de su soporte social y se tomaron medidas de la dinamometría de ambas manos. Se procedió al análisis inferencial usando el coeficiente de correlación de Spearman (rs) entre la AF total y las diferentes categorías por intensidad contabilizada por el ActiGraph, y la recogida por el IPAQ. Los datos fueron comparados en min/día realizando actividad sedentaria, ligera, moderada o intensa. Resultados: No se encontró concordancia entre los datos arrojados por ambos instrumentos, a excepción de la categoría sedentaria/sentado, con un rs=0,714 (p=0,02). Los minutos/día totales de AF del acelerómetro ha sido un 263% más elevados que del cuestionario, por lo que este último infravalora la AF. Respecto a las dimensiones emocionales evaluadas, la confusión/aturdimiento se relacionó significativamente con la sensación de fatiga (rs=0,85, p=0,002) y la fatiga total (rs=0,71, p=0,02). También apareció una relación inversa entre vigor/actividad y la dimensión cognitiva de la fatiga (rs=-0,63, p=0,04). La sensación de fatiga/inercia también se relacionó inversamente con la fuerza prensil de la mano del lado intervenido. También fue inversa la relación entre el soporte familiar y de amigos y el tiempo en posición tumbado o en decúbito (rs=-0,77, p=0,008 y rs=-0,84, p=0,002, respectivamente) y entre este apoyo de los amigos y la rabia/hostilidad (rs=-0,64, p=0,04) Conclusiones: Había un grado de acuerdo limitado en la medida de la AF y las conductas sedentarias del IPAQ y del Actigraph. El primero no parece ser muy adecuado para esta población, y para el acelerómetro necesitaríamos valores de referencia más en consonancia con estas mujeres

Primary objective: To analyse the level of agreement between that measured by the self-report provided by the IPAQ (International Physical Activity Questionnaire) and the objective measurement provided by accelerometers (ActiGraph) in breast cancer patients. Secondary objective: To evaluate the perception of their fatigue in these patients, as well as their state of mind and prehensile strength. An attempt was also made to determine the relationship between social support and the practice of physical activity. Material and method: The 10 patients carried an accelerometer for 9 days, and afterwards they completed the IPAQ, Piper Fatigue Scale (PFS), and Profile of Mood States (POMS) questionnaires. Their social support was also assessed, and dynamometry measurements were taken on both hands. An inferential analysis was performed using the Spearman correlation coefficient (rs) between the total physical activity (PA) and the different categories by the intensity measured by ActiGraph, and that recorded in the IPAQ. The data were compared in minutes/day of sedentary, light, moderate or intense activity. Results: No agreement was found between the data provided by both tools, with the exception of the sedentary/seated category with a Spearman coefficient (rs) of 0.714 (P=.02). The total minutes/day of the accelerometer was 263% higher than the questionnaire, thus this latter undervalued the PA. As regards the emotional dimensions evaluated, confusion/bewilderment was significantly associated with feeling of fatigue (rs=0.85, P=.002), and total fatigue (rs=0.71, P=.02). An inverse relationship was also observed between vigour/activity and cognitive dimension of fatigue (rs=-0.63, P=.04). The feeling of fatigue/inertia was also inversely associated with prehensile strength of the hand on the side of the intervention. There was also an inverse relationship between family and friends support and the time in the lying down or decubitus position (rs=-0.77, P=.008 and rs=-0.84, P=.002, respectively) and between this support by friends and anger/hostility (rs=-0.64, P=.04)Conclusions: There was a limited level of agreement in the measurement of PA and sedentary behaviours of the IPAQ and Actigraph. The first one does not seem to very suitable for this population, and reference values more in line with these women are needed for the accelerometer

Bevacizumab for recurrent, persistent or advanced cervical cancer: reproducibility of GOG 240 study results in "real world" patients.

PURPOSE: Bevacizumab is the only therapeutic target approved for patients with persistent, recurrent or advanced cervical cancer from a phase III study that combined with chemotherapy; it proves a significant increase in overall survival. To retrospectively assess the efficacy and safety of bevacizumab as the first-line treatment in patients from usual clinical practice with recurrent/persistent or advanced cervical cancer. PATIENTS AND METHODS: Treatment consisted of cisplatin 50 mg/m2 or carboplatin AUC 5 plus paclitaxel 175 mg/m2 for 6-8 cycles and bevacizumab 15 mg/kg every 3 weeks up to progression or unacceptable toxicity. The endpoints were progression-free survival (PFS), overall survival (OS), response rates (RR) and toxicity. RESULTS: Twenty-seven patients were included from January 2014 to June 2017, with a median follow-up 10, 1 months. Eleven percent had recurrent/persistent disease and 89% had metastatic disease at diagnosis. The prior exposition to platinum was 70%. The median PFS and OS were 9, 6 and 21, 5 months, respectively. There was an increase of fistula formation (22%). All of them had pelvic and peritoneal disease at the beginning of treatment and previous treatment with chemoradiotherapy; non-incidence differences were found according to the type of platinum agent used. There were two treatment-related deaths, one from intestinal perforation and another from severe sepsis. CONCLUSION: Finally, although our study does have certain limitations, we believe that it can provide useful information and encouraging evidence that the routine use of bevacizumab as part of first-line treatment of patients with advanced cervical cancer may be associated with outcomes comparable with those obtained in GOG240 study.

Subcellular localisation of pMEK has a different prognosis in locally advanced head and neck cancer treated with concomitant radiochemotherapy.

BACKGROUND: MEK1 (MAP2K1) and MEK2 (MAP2K2) are closely related dual-specificity protein kinases which function by phosphorylating both serine/threonine and tyrosine residues of their substrates ERK1 and ERK2, controlling fundamental cellular processes that include cell growth and proliferation. To investigate the prognostic significance of pMEK expression in the nucleus and cytoplasm among patients with locally advanced head and neck cancer treated with concurrent radiochemotherapy. METHODS: Immunohistochemistry was performed on the retrieved archival tissue of 96 patients to detect pMEK, p53 and Ki-67. RESULTS: Sixty-six percent of patients were positive for pMEK expression in the nucleus and 41 % in cytoplasm. On univariate analysis, high nuclear pMEK was predictive of worse 5y-DFS and 5y-OS, with a trend to significance (26 % vs. 41 %, p = 0.09; 36 % vs. 47 %, p = 0.07). High cytoplasmic pMEK was predictive of better 5-y OS and 5-y DFS outcomes (61 % vs. 27 %, p = 0.01; 46 % vs. 22 %, p = 0.02). On multivariate analysis, low cytoplasmic pMEK and high nuclear pMEK predicted worse DFS and OS (p = 0.01; p = 0.04 and p = 0.02; p = 0.02 respectively). CONCLUSIONS: Subcellular localisation of pMEK has different prognosis in locally advanced head and neck cancer treated with radiochemotherapy.

Concurrent radiotherapy plus epidermal growth factor receptor inhibitors in patients with human papillomavirus-related head and neck cancer

PURPOSE: Concurrent radio-chemotherapy (RT-CT) is the standard treatment for locally advanced head and neck squamous cell carcinoma (LA-HNSCC), but RT plus epidermal growth factor receptor (EGFR) inhibitors is an effective option when CT is not appropriate. Human papillomavirus (HPV) is associated with an improved prognosis in LA-HNSCC; however, it has not been fully studied as a prognostic factor after RT + EGFR inhibitors. EXPERIMENTAL DESIGN: Immunohistochemical expression of p16INK4A and PCR of HPV16 DNA were retrospectively analyzed in tumor blocks from 52 stage III/IV LA-HNSCC patients treated with RT + EGFR inhibitors. Disease-free survival (DFS) and overall survival (OS) were analyzed by the Kaplan-Meier method. RESULTS: DNA of HPV16 was found in six of 52 tumors (12 %) and p16 positivity in eight tumors (15 %). After a median follow-up time of 45 months (6-110), p16-positive patients treated with RT + EGFR inhibitors showed an improved DFS (2-year DFS 75 vs. 44 %, HR 0.25, 95 % CI 0.06-0.99, p = 0.047) compared with p16-negative patients. These differences were outperformed when compared by HPV16 status (2-year OS rates of 83 vs. 58 %, HR 0.17, 95 % CI 0.02-0.99, p = 0.049 and 2-year DFS rates of 83 vs. 45 %, HR 0.17, 95 % CI 0.02-0.99, p = 0.049). In the Cox regression analysis with OS as the end point, ECOG 0-1 was the only prognostic factor independently associated with a good prognosis in the multivariable analysis. CONCLUSION: In this study, p16/HPV16-positive patients with LA-HNSCC treated with RT + EGFR inhibitors showed a better survival, not confirmed in multivariate analysis (AU)

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Concurrent radiotherapy plus epidermal growth factor receptor inhibitors in patients with human papillomavirus-related head and neck cancer.

PURPOSE: Concurrent radio-chemotherapy (RT-CT) is the standard treatment for locally advanced head and neck squamous cell carcinoma (LA-HNSCC), but RT plus epidermal growth factor receptor (EGFR) inhibitors is an effective option when CT is not appropriate. Human papillomavirus (HPV) is associated with an improved prognosis in LA-HNSCC; however, it has not been fully studied as a prognostic factor after RT + EGFR inhibitors. EXPERIMENTAL DESIGN: Immunohistochemical expression of p16INK4A and PCR of HPV16 DNA were retrospectively analyzed in tumor blocks from 52 stage III/IV LA-HNSCC patients treated with RT + EGFR inhibitors. Disease-free survival (DFS) and overall survival (OS) were analyzed by the Kaplan-Meier method. RESULTS: DNA of HPV16 was found in six of 52 tumors (12 %) and p16 positivity in eight tumors (15 %). After a median follow-up time of 45 months (6-110), p16-positive patients treated with RT + EGFR inhibitors showed an improved DFS (2-year DFS 75 vs. 44 %, HR 0.25, 95 % CI 0.06-0.99, p = 0.047) compared with p16-negative patients. These differences were outperformed when compared by HPV16 status (2-year OS rates of 83 vs. 58 %, HR 0.17, 95 % CI 0.02-0.99, p = 0.049 and 2-year DFS rates of 83 vs. 45 %, HR 0.17, 95 % CI 0.02-0.99, p = 0.049). In the Cox regression analysis with OS as the end point, ECOG 0-1 was the only prognostic factor independently associated with a good prognosis in the multivariable analysis. CONCLUSION: In this study, p16/HPV16-positive patients with LA-HNSCC treated with RT + EGFR inhibitors showed a better survival, not confirmed in multivariate analysis.

Tyrosine kinase inhibitors and drug interactions: a review with practical recommendations

The adverse effects associated to traditional chemotherapy are well known and broadly studied. In the recent years several tyrosine kinase inhibitors have been approved for cancer treatment and numerous are under investigation. These drugs target specific mutated/overexpressed tyrosin kinase receptors and frecuently their pharmacokinetic/pharmacodinamic behavior is not fully elucidated. These new drugs may interact with non-antineoplastic drugs leading to undesirable adverse effects. In this article, we will discuss different types of drug interactions and briefly review the pharmacokinetics and mechanisms of action of tyrosine kinase inhibitors in clinical use, with a particular emphasis on the risk of the occurrence of such interactions based on currently available scientific evidence (AU)

Multimodal treatment of desmoid tumours: the significance of local control

INTRODUCTION: Desmoid tumours are a rare group of tumours arising in the deep musculoaponeurotic structures and although they have no metastatic potential they can be locally aggressive with relapse rates of between 23-40%. Three sub-sites are reported: extra-abdominal, abdominal wall and intra-abdominal. The purpose of this study was to analyze patients with these tumours treated and followed at our institution and to determine factors influencing disease free survival. MATERIAL AND METHODS: We conducted a retrospective study of 20 patients treated between 1997 and 2009. Data was compiled to include age, gender, surgical history, familial adenomatous polyposis (FAP), contraceptives, tumour site, first-line treatment, positive margins and adjuvant radiotherapy. A descriptive and survival statistical analysis was also performed. RESULTS: Most patients were women, with a median age of 36 years, with abdominal wall involvement and treated with complete surgery without adjuvant radiotherapy. With a median follow-up of 35 months (range 0-188), local control at 5 years for any kind of treatment was 80%. Overall survival (OS) and 5-year progression-free survival (PFS) were 100% and 86%, respectively. CONCLUSION: Desmoid tumours are group of rare tumours. Although complete surgical resection remains the cornerstone of treatment for resectable lesions, there is still substantial risk of recurrence. Our outcomes are comparable to those reported in the few series published to date (AU)

Insidious mastalgia hiding a desmoid tumour of the breast

Fibromatosis is a rare, locally aggressive and bening breast tumor that presents problems in the diagnosis and may mimic breast cancer on physical examination, mammography and breast ultrasound. Definitive diagnosis is reached by histologic findings. This case shows the unusual presentation in our patient and management of this unfrecuent desmoid tumor (AU)

Combined oral cyclophosphamide and bevacizumab in heavily pre-treated ovarian cancer

INTRODUCTION: Metronomic chemotherapy combined with bevacizumab has proved to be effective in various tumour types. The aim of this study is to review our experience in recurrent ovarian carcinomas treated with low-dose cyclophosphamide and bevacizumab. MATERIALS AND METHODS: Retrospective analysis of pre-treated ovarian cancer patients, i.e., > or =2 previous chemotherapy regimens who received treatment with oral cyclophosphamide 50 mg/day and bevacizumab 10 mg/kg IV every two weeks. Patients with a performance status 0-2 were included. The endpoints were response rates, progressionfree disease and safety profile. RESULTS: Nine patients with advanced, measurable ovarian cancer were included. Of these, 8 were platinum-resistant and had received prior regimens with gemcitabine (88%), topotecan (77%) and liposomal doxorubicin (66%). There was a mean of 5 previous lines of ch

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