Emerging histological and serological biomarkers in oral squamous cell carcinoma: Applications in diagnosis, prognosis evaluation and personalized therapeutics (Review).

Oral squamous cell carcinoma (OSCC) is the most common malignancy of the oral cavity and accounts for >90% of all oral cancers. Despite advances in diagnostic procedures and therapeutic interventions, overall survival has not improved significantly in recent decades, primarily due to late diagnosis, locoregional recurrence and treatment resistance. Identifying reliable biomarkers for early detection, prognosis evaluation and treatment response prediction is critical for improving clinical outcomes in patients with OSCC. In the present review, the prognostic and predictive utility of circulating biomarkers, such as circulating tumour cells, serological biomarkers and histological and genetic biomarkers, were explored in the context of OSCC. In addition, the potential role of immune checkpoints in the treatment of OSCC was highlighted and the rapidly evolving field of liquid biopsy and its potential to revolutionize diagnosis, prognosis evaluation and treatment were examined. The existing evidence for the clinical utility of these biomarkers was critically evaluated and the challenges and limitations associated with their introduction into routine clinical practice were addressed. In conclusion, the present review highlights the promising role of biomarkers in improving the current understanding of the pathogenesis of OSCC and offers potential avenues for improving patient care through personalized medicine approaches.

Sunitinib rechallenge in advanced renal cell carcinoma: outcomes of a multicenter retrospective study.

PURPOSE: The aim of this multicenter study was to evaluate the clinical outcomes of patients with metastatic renal cell carcinoma (mRCC) who received sunitinib retreatment. METHODS: Clinical data from patients treated with sunitinib rechallenge in nine Spanish centers were retrospectively analyzed. All patients received first-line sunitinib until progression or intolerance, followed by one or more successive drugs and rechallenge with sunitinib thereafter. RESULTS: Thirty-seven patients were included. At first-line treatment, objective response rate (ORR) was 69.4% and median progression-free survival (PFS) was 19.4 months. At rechallenge, ORR was 27.2% and 39.4% of patients obtained stabilization of disease. Median PFS was 6.2 months. Clinical benefit was obtained by 21 patients (75%) with > 6-month interval between sunitinib treatments and by 1 patient (20%) among those with ≤ 6-month interval (P = 0.016). Hemoglobin levels ≥ lower level of normal were associated with clinical benefit (P = 0.019) and with PFS (P = 0.004). Median overall survival from start of first-line sunitinib was 52.7 months. No new adverse events were observed at rechallenge. CONCLUSIONS: Sunitinib rechallenge is a feasible treatment option for selected patients with mRCC.

Management of Infection and Febrile Neutropenia in Patients with Solid Cancer. / Manejo de la infección y la neutropenia febril en el paciente con cáncer sólido.

A group of experts from the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) and the Spanish Society of Medical Oncology (SEOM) have reviewed in this paper the main aspects to be considered in the evaluation of patients with solid cancer and infectious diseases. They have established a series of recommendations on the prevention of the most prevalent infections in these patients, the use of vaccines, the control measures of vascular catheter infection and prevention of infections before certain surgical procedures. Also the criteria for management of febrile neutropenia and the use of colony-stimulating factors were revised. Finally they provide a series of recommendations for the treatment of cancer patients with severe infection. The document is completed with a series of measures for the control of hospital infection.

Quality Indicators to Assure and Improve Cancer Care in Spain Using the Delphi Technique.

BACKGROUND: The quality of cancer care has become a priority for health care systems. The goal of this research was to develop a set of evidence-based quality indicators (QIs) for organization, palliative care, and colorectal, breast, and lung cancers for introducing a system of benchmarking in Spain. METHODS: A comprehensive evidence-based literature search was performed to identify potential QIs. An expert panel (the health care quality promotion group) of 9 oncologists identified indicators and evaluated them. A Delphi process involving 58 physicians was used to rank QIs by clinical relevance (validity). The expert panel then evaluated the selected indicators in terms of the feasibility of measuring them in Spanish hospitals, their usefulness for comparisons, their degree of clinical relevance, and their sensitivity to the impact of health care improvements. RESULTS: From the literature review, 99 potential QIs were identified. The Delphi process shortened the list to 72 QIs. A final set of 57 QIs was established by the health care quality promotion group: 12 related to organizational issues, 11 to colorectal cancer, 11 to breast cancer, 12 to lung cancer, and 11 to palliative care. This final set included structure (n=2), process (n=36), and outcome (n=19) indicators. CONCLUSIONS: A set of QIs has been developed using a validated Delphi method, meaning that we can be confident of their validity, feasibility, sensitivity, and acceptability. These QIs are to serve as the basis of a strategy for benchmarking across oncology services in Spanish hospitals and should enable us to assure and improve the quality of cancer care.

Factors Associated with the Selection of First-line Bevacizumab plus Chemotherapy and Clinical Response in HER2-negative Metastatic Breast Cancer: ONCOSUR AVALOX Study.

AIM: To evaluate factors associated with the selection of first-line bevacizumab plus chemotherapy and clinical response in HER2-negative metastatic breast cancer (MBC) in clinical practice in Spain. PATIENTS AND METHODS: All consecutive adult female patients with HER2-negative MBC who had received first-line bevacizumab plus chemotherapy for at least 3 months were enrolled in the present study. RESULTS: A total of 292 evaluable patients were included; 25% had triple-negative breast cancer (TNBC) and 75% had hormone receptor-positive breast cancer (HRPBC). Nearly 40% of patients had ≥3 metastatic sites, mainly located in the bone (48%) and liver (40%). Bevacizumab was mostly combined with paclitaxel (67.1%). ER-positive tumors were only identified as an independent factor associated with the choice of treatment (odds ratio (OR): 0.538; p=0.02). The overall response rate (ORR) was 63.7% (TNBC: 57.5%; HRPBC: 65.9%). Patients aged 36-50 years (OR: 3.03; p=0.028) and those with metastases at sites other than the bone (OR: 0.38; p=0.001) and ≥3 metastatic sites (OR: 1.41; p=0.018) were more likely to achieve objective responses. CONCLUSION: First-line bevacizumab plus chemotherapy, mainly paclitaxel, is an effective and well-tolerated treatment option for HER2-negative MBC, particularly in more aggressive disease.

Updated recommendations from the Spanish Oncology Genitourinary Group for the treatment of patients with metastatic castration-resistant prostate cancer.

Prostate cancer is the most prevalent male urogenital malignancy. Approximately 30% of patients with prostate cancer will develop advanced disease. Androgen deprivation therapy achieves disease control in about 90% of these patients, but the majority of them will eventually develop progressive disease, a status called castration-resistant prostate carcinoma (CRPC). However, in recent years, several new therapy strategies, such as immunotherapy, hormonal manipulations, chemotherapy agents and some bone-targeted therapies, have demonstrated an improvement in terms of overall survival in controlled trials. In 2012, the Spanish Oncology Genitourinary Group (SOGUG) published its recommendations for the treatment of patients with CRPC. Due to the recent appearance of important new data and the complexity of decision-making in this field, SOGUG herein provides updated recommendations for the treatment of patients with metastatic prostate cancer.

Controversies in the treatment of invasive urothelial carcinoma: a case report and review of the literature.

BACKGROUND: More than 429,000 patients worldwide are diagnosed with bladder cancer each year and muscle-invasive bladder cancer has an especially poor outcome. The median age at diagnosis is over 70 years, and many patients also have a substantial number of age-associated impairments that need to be considered when planning therapeutic interventions. CASE PRESENTATION: Here, we report the case of a 63-year-old man with a cT3b urothelial carcinoma which was surgically removed. No neoadjuvant or adjuvant chemotherapy was administered. After 18 months a lung metastasis was confirmed and resected but no chemotherapy was given after surgery. Twelve months later, the patient relapsed and was treated with a combination of gemcitabine and cisplatin and after a decline in renal function the treatment was changed to a combination of carboplatin and gemcitabine which resulted in a partial response which lasted 8 months. Following this vinflunine was administered as a second line treatment. Here we review the evidence available in the literature regarding the suitability of different treatment options for managing muscle-invasive bladder cancer at each step of the case presentation. CONCLUSION: Bladder cancer treatment requires a multidisciplinary approach. Although, depending on the clinical characteristics of the patient, there are some controversial points in the management of this pathology we hope that the scientific data and the clinical trials reviewed in this case report, can help to guide physicians to make more rational decisions regarding the management of these patients.

Usefulness of the PERFORM questionnaire to measure fatigue in cancer patients with anemia: a prospective, observational study.

BACKGROUND: The PERFORM Questionnaire is a 12-item scale developed for assessing fatigue in cancer patients in the clinical practice. It has advantages over other tools in that it is short and includes beliefs and attitudes of patients about fatigue. It was psychometrically validated in cancer patients with and without anemia. PURPOSE: We evaluated the usefulness of the PERFORM scale to measure fatigue in a large study focusing exclusively on anemic patients. METHODS: This was an observational, multicenter, prospective, 3-month study in cancer patients with hemoglobin (Hb)≤11 g/dl. Fatigue was assessed using the PERFORM questionnaire. The overall score ranges from 12 (no fatigue) to 60 (maximum fatigue). RESULTS: We included 667 patients: 54.1 % women, mean age 60 (standard deviation, 12) years. A highly significant, but mild correlation was observed between low baseline Hb and high patient perception of fatigue (r with PERFORM score=-0.215, p < 0.0001). Of the patients, 65.8 % improved Hb level during follow-up (increase of ≥1 g/dL and/or achieving >11 g/dL), which translated into a significant improvement in the PERFORM score [mean (95 % confidence interval (CI)] change, -1.2 (-0.04 to -2.4), whereas more fatigue was observed in patients without improvement in Hb [change (95 % CI) in PERFORM, +3.3 (1.5 to 5)]. In a multivariate linear regression analysis, the independent factors associated to fatigue at 3 months were a low Hb level, a low Karnofsky index, active chemotherapy, cancer treatment with palliative intention, and transfusion need in the last 3 months. CONCLUSIONS: Minimal increases or decreases in Hb of ≥1 g/dL were associated with meaningful changes in patient-perceived fatigue as measured with the PERFORM questionnaire. In addition to anemia severity, other factors such as active chemotherapy and advanced disease contribute to perception of fatigue by cancer patients.

New primary ipsilateral metachronous breast tumor: a case report.

After breast-conserving treatment, the occurrence of ipsilateral breast tumor relapse raises the concern regarding whether it may represent two distinct types of lesion that it is important to define, a true recurrence (TR) or a new primary tumor (NPT). TR and NPT have different natural histories, prognosis, and in turn different implications for therapeutic management. We report the case of a 35-year-old woman who developed a breast invasive ductal carcinoma, which after receiving breast-conserving treatment with adjuvant chemotherapy, radiotherapy and hormone therapy, developed four years after an inflammatory carcinoma in the same breast, with different expression of immunohistochemical markers than the first breast cancer. The patient was treated with neoadjuvant chemotherapy that allowed the realization of a radical mastectomy with a complete pathological response. We describe the diagnostic and therapeutic approach of ipsilateral breast tumor relapses, along with a review of existing literature.

Treatment of cancer pain: Spanish Society of Medical Oncology (SEOM) recommendations for clinical practice.

Cancer pain should be controlled in most patients, however this is not always achieved. These guidelines describe the classification, evaluation and treatment of chronic cancer pain in accordance with the WHO treatment strategy of pain stages: mild, moderate and severe. For treatment during the third stage, we cover titration and rotation of opioids, as well as their side effects and prevention. Also described is neuropathic pain and refractory pain, coadjuvant treatments and non pharmacological analgesic treatments. Finally, treatment of breakthrough pain is defined.

Recommendations from the Spanish Oncology Genitourinary Group for the treatment of patients with metastatic castration-resistant prostate cancer.

Prostate cancer is the most prevalent urogenital malignancy. However, despite initial disease control using androgen deprivation, most of patients eventually develop progressive disease that is resistant to further hormone manipulation. For these patients with castration-resistant prostate cancer (CRPC), and particularly patients with metastatic disease, options have been limited, and prognosis is grim. However, as newer regimens and agents become available, higher rates of objective and biochemical response are being achieved, providing renewed hope for the management of these patients. With the aim of facilitating the treatment of these patients, the Spanish Oncology Genitourinary Group (SOGUG) has issued a series of the recommendations which have been collected in this review. Each recommendation is accompanied by the appropriate level of evidence and grade of recommendation on the basis of the characteristics of the data available.

Experience in the use of sunitinib given as a single agent in metastatic chemoresistant and castration-resistant prostate cancer patients.

OBJECTIVE: Vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) correlate with poor prognosis in castration-resistant prostate cancer (CRPC). Sunitinib has shown activity in CRPC and at the time of this analysis there was no standard therapy for docetaxel-refractory CRPC. METHODS: We present a case series data collection of 19 patients with a median age of 73 years, CRPC and rising prostate-specific antigen (PSA). Patients received sunitinib 37.5 mg continuous daily dose. One cycle comprised a 4-week period. Patients were evaluated by CT scan every 8 weeks and PSA was monitored every 4 weeks. RESULTS: Median Eastern Cooperative Oncology Group (ECOG) performance status score was 2. Patients received a median of two previous treatment lines for the hormone-refractory setting. Baseline median PSA was 280 ng/ml. Patients received a median of 16 weeks of therapy (4 - 48+). One patient achieved a partial response (5%) and 12 (66.7%) achieved stable disease for at least 3 months according to RECIST criteria. Median progression-free survival was 4 months. PSA declined > 50% in 5/19 (26.3%) and stabilized in 7/19 (37%) patients. Frequent adverse events were grade 3 asthenia (21%), grade 3 diarrhea (10%) and grade 3 hand-foot syndrome (15.7%). CONCLUSIONS: Activity with sunitinib was observed in highly pretreated docetaxel-refractory CRPC with acceptable tolerability. Additional studies should confirm the role of antiangiogenic agents in this setting.

Psychometric properties of the Perform Questionnaire: a brief scale for assessing patient perceptions of fatigue in cancer.

PURPOSE: Fatigue is a symptom with a relevant impact on the daily lives of cancer patients and is gaining importance as an outcome measure. The Perform Questionnaire (PQ) is a new scale originally developed among Spanish-speaking patients for the assessment of perception and beliefs about fatigue in cancer patients. METHODS: An observational longitudinal multicenter study was carried out on cancer patients with fatigue. Fatigue-specific measures (FACT-F), generic health-related quality-of-life measures (NHP), and PQ were gathered at baseline and 3 months later. Feasibility, reliability (internal consistency and test-retest), validity, sensitivity to change, and minimally important differences were analysed. RESULTS: Four hundred thirty-seven patients were included in the study: 60.5% were women, the mean age was 59.1 years, the mean time from diagnosis was 2.2 years, 33.6% of patients had breast cancer, and 29.1% had anaemia (haemoglobin (Hb) <11 g/dL). Low levels of missing items and ceiling/floor effects (<10%) were found. The overall Cronbach's alpha and intraclass correlation coefficient were 0.94 and 0.83, respectively. The PQ score was associated with fatigue intensity, the need for a caregiver, and the Hb level. Its association was stronger with the FACT-F than with non-specific health measures (NHP). The PQ showed good sensitivity to change for improved and worsening health status. A minimally important difference of 3.5 was estimated in patients whose Hb level had improved by at least 1 g/dL. CONCLUSIONS: The PQ measured the attitudes and beliefs about fatigue among cancer patients in clinical practice and showed good psychometric properties among Spanish-speaking patients.

An unusual metastatic renal cell carcinoma with maintained complete response to sunitinib treatment.

Recently, metastatic renal cell carcinoma (mRCC) treatment has changed dramatically with the onset of new therapies against molecular targets replacing immunotherapy as standard treatment. We report the case of a 49-year-old patient with a moderately differentiated renal clear cell carcinoma without extracapsular extension who underwent radical nephrectomy. Eight months after surgery, he developed a thyroid metastasis which was also treated surgically with a hemithyroidectomy. Seventy-five months after nephrectomy, the patient presented an upper gastrointestinal bleeding due to a duodenal metastasis that infiltrates the head of the pancreas. The treatment applied was surgery by duodenopancreatectomy, with positive surgical margins in the pathologic study. In addition to this, the extension study showed lung metastases requiring initiation of systemic treatment with sunitinib. The patient presented an excellent response to treatment, showing complete clinical and radiological response at 5 months of treatment (RECIST criteria) and a disease-free survival of 48 months until now, without evidence of toxicity. RCC has the potential to metastasize to almost any location, but thyroid and duodenal metastases in RCC are extremely rare. Moreover, this case also highlights the good responses that can be achieved in terms of disease-free survival, low toxicity and quality of life in this new era of therapies against molecular targets.

Integration of panitumumab into the treatment of colorectal cancer.

Conventional chemotherapy increases progression-free survival (PFS) and overall survival (OS) of metastatic colorectal cancer (mCRC) patients versus best supportive care (BSC). However, the efficacy of chemotherapy is limited. Recently approved monoclonal antibodies (MoAb) have a different mechanism of action, targeting growth factors or their receptors. Panitumumab is a fully human IgG2 MoAb directed against the epidermal growth factor receptor (EGFR). In phase II trials, panitumumab showed preliminary activity in chemorefractory mCRC. This efficacy was confirmed in a randomized pivotal phase III trial, which compared single-agent panitumumab plus BSC versus BSC alone. Several ongoing clinical trials are evaluating panitumumab in combination with different chemotherapy regimens in first- and second-line settings. Skin toxicities, hypomagnesemia, and diarrhea are the most common adverse events associated with anti-EGFR therapy. KRAS status and skin rash have been correlated with panitumumab efficacy. This article reviews the preclinical and pharmacokinetics data, activity and tolerance of panitumumab in mCRC patients. Potential predictive factors of response are also discussed.

Adjuvant chemotherapy for stages II, III and IV of colon cancer.

Colorectal cancer is the third most frequent malignant neoplasm in Western countries. After complete resection, 5-year overall survival varies according to the initial stage. Adjuvant chemotherapy (CT) is indicated in patients with colon cancer at high-risk stage II, stage III and after complete resection of metastases. 5-Fluorouracil (5FU), alone or modulated with levamisol or leucovorin (LV), oral fluoropyrimidines, raltitrexed, irinotecan and oxaliplatin have been studied as adjuvant therapy for colon cancer. Nowadays, oxaliplatin-based regimens, FOLFOX or FLOX, are considered as the standard adjuvant CT. If there are contraindications for oxaliplatin, the best alternatives are capecitabine or continuous infusion of 5FU/LV. The role of monoclonal antibodies, cetuximab and bevacizumab, combined with oxaliplatin/fluoropyrimidine-based CT is under investigation in clinical trials. This article reviews the state of the art and the future perspectives of adjuvant therapy in colon cancer. Prognostic and predictive factors are also commented on.

Development of a new questionnaire to assess patient perceptions of cancer-related fatigue: item generation and item reduction.

OBJECTIVES: Existing instruments that measure the impact of cancer-related fatigue on health-related quality of life do not usually incorporate the attitudes, beliefs and perspectives of patients. This study aimed to develop an instrument to measure the impact of cancer-related fatigue on the health-related quality of life of cancer patients. METHODS: Items were generated from a literature review, focus groups of cancer patients and meetings with oncologists. Potential items were administered to cancer patients to facilitate item reduction, which was based on clinimetric and psychometric analyses and qualitative criteria. A preliminary assessment of feasibility, reliability and validity of the retained items was performed. RESULTS: An initial pool of 75 items was administered to 238 cancer patients. Fifty items were eliminated after statistical analysis and 13 in response to expert opinion, resulting in a provisional instrument with 12 items in 3 dimensions. These displayed acceptable internal consistency (Cronbach's alpha, 0.78-0.92) and their overall score was associated with fatigue intensity, extent of disease, intention of treatment and need of caregivers. CONCLUSION: The newly developed questionnaire, which measures the impact of cancer-related fatigue on oncology patients, has shown satisfactory feasibility, reliability and validity.

Role of tyrosine kinase inhibitors in the treatment of advanced colorectal cancer.

Colorectal cancer (CRC) is a common health problem in Western countries. In advanced disease, either FOLFOX (oxaliplatin/5-fluorouracil [5-FU]/leucovorin [LV]) or FOLFIRI (irinotecan/LV/5-FU) are accepted first-line chemotherapy regimens, but median survival appears to plateau with a chemotherapy-only approach. The use of epidermal growth factor receptor (EGFR)- and vascular endothelial growth factor (VEGF)-targeting monoclonal antibodies has increased the median survival of patients with advanced CRC beyond 20 months. However, the precise role of cetuximab, panitumumab and bevacizumab in combination with different chemotherapeutic regimens is still being determined in first- and second-line settings. The activity and tolerance of the EGFR tyrosine kinase inhibitors (TKIs), gefitinib erlotinib, and EKB-569, alone or in combination with chemotherapy, have been explored in patients with metastatic CRC. Regarding VEGF receptor TKIs, 2 phase III clinical trials determined the role of vatalanib in combination with FOLFOX. Efficacy of the oral multitargeted TKIs sorafenib and sunitinib is under investigation. This article aims to review the role of TKIs in advanced CRC.

Multicenter phase II study of fixed sequences of capecitabine combined with oxaliplatin or irinotecan in patients with previously untreated metastatic colorectal cancer.

PURPOSE: The purpose of this study was to evaluate the antitumor activity and toxicity of fixed sequences of capecitabine/oxaliplatin followed by capecitabine/irinotecan in patients with previously untreated metastatic colorectal cancer. PATIENTS AND METHODS: Adult patients with histologically confirmed, previously untreated, nonresectable, locally advanced or metastatic colorectal adenocarcinoma were enrolled in the study. Patients were treated as follows: capecitabine (1000 mg/m2 orally twice daily) on days 1-14 and oxaliplatin (130 mg/m2 2-hour intravenous infusion) on day 1, followed by capecitabine (1000 mg/m2 twice daily) on days 1-14 and irinotecan (240 mg/m2 1.5-hour intravenous infusion) on day 1. Each combination was administered every 21 days during 4 consecutive cycles followed by the alternating sequence to a maximum of 16 cycles. RESULTS: A total of 35 eligible patients have been included in this ongoing study. Response rate (complete responses plus partial responses) was 37.1%. With a median follow-up of 9.5 months, the median time to disease progression and overall survival were 7.4 months and 16.4 months, respectively. Treatment was well tolerated, with only 6% of the patients developing grade 3/4 neurotoxicity. However, the low number of patients treated beyond 4 cycles limits the interpretation of the data. CONCLUSION: The preliminary results from this ongoing study suggest the feasibility of this strategy, which resulted in promising antitumor activity with less neurotoxicity.

Activity and safety of oxaliplatin with weekly 5-fluorouracil bolus and low-dose leucovorin as first-line treatment for advanced colorectal cancer.

This study was designed to evaluate the safety and tolerability of oxaliplatin combined with weekly boluses of 5-fluorouracil (5-FU) and low doses of leucovorin (LV) and to determine objective response, progression-free survival, and overall survival of patients with previously untreated advanced colorectal cancer. Seventy-nine patients enrolled in an observational, multicenter, prospective, open-label phase II study received intravenous (I.V.) infusions of oxaliplatin 85 mg/m2 over the course of 2 hours on days 1 and 14 and LV 20 mg/m2 over the course of 2 hours and 5-FU 500 mg/m2 as a bolus on days 1, 7, and 14 every 4 weeks until disease progression or unacceptable toxicity occurred. Seventy-nine patients were evaluable for safety, and data from 70 patients were used for efficacy analysis. The objective response rate was 51.4%. Complete responses occurred in 7 patients (10%), and partial responses occurred in 29 patients (41.4%). Disease control, defined as response or stable disease, was obtained in 56 of 70 patients (80%). The median duration of response was 8.34 weeks (range, 7.3-11.5 weeks). The median time to progression was 7.13 months (range, 6.28-7.72 months), and median overall survival time was 15 months (range, 12.32-18.37 months). Acute dose-limiting toxicities were grade 3/4 diarrhea and neutropenia, which occurred in 10.5% and 3.9% of patients, respectively. Among the 70 patients who experienced neurosensory toxicity, it was estimated that only 1.3% had grade 3 symptoms. Preliminary data showed that the regimen is at least as active as other regimens combining oxaliplatin and infusional schedules of 5-FU and might be more convenient for patients because it avoids the need for I.V. catheter implantation.