Rare case of chemotherapy-refractory metastatic vaginal squamous cell carcinoma with complete response to concurrent pembrolizumab and radiotherapy- case report and literature review.

Primary vaginal cancer is a rare malignancy with a lack of international guidelines and supporting clinical trial evidence to guide decision making. Historical results have shown poor outcomes with chemotherapy for stage IVB vaginal squamous cell carcinoma (SCC). The evolving role of checkpoint inhibitors in rare gynaecological cancers prompted us to investigate the role of pembrolizumab in this setting.

Concurrent use of nivolumab and radiotherapy for patients with metastatic non-small cell lung cancer and renal cell carcinoma with oligometastatic disease progression on nivolumab.

Checkpoint inhibitors (CPIs), such as nivolumab, have transformed the treatment paradigm for patients with metastatic non-small cell lung cancer (mNSCLC) and metastatic renal cell carcinoma (mRCC). The combination of CPIs and radiotherapy (RT) constitutes a multimodal treatment approach that may work synergistically and facilitate augmented systemic responses. The aim of the present retrospective study was to assess the efficacy and safety of continuation of nivolumab treatment with the addition of RT in patients with mNSCLC and mRCC who develop oligometastatic disease progression on single-agent nivolumab.

Rare Case of Intracardiac Renal Cell Carcinoma Metastasis with Response to Nivolumab: Case Report and Literature Review.

Intracardiac metastases in the absence of inferior vena cava involvement is a rare occurrence in patients with metastatic renal cell carcinoma (mRCC). There is limited evidence regarding the efficacy and safety of standard treatment modalities for mRCC patients with intracardiac metastases. Presence of intracardiac metastases is known to indicate poor prognosis and may potentially increase risk of treatment-related complications.

Elective Management of the Neck in Parotid Tumours.

Aims: Management of the clinically node-negative (cN0) neck for parotid tumours remains controversial. Options include observation, elective neck dissection (END) or elective nodal irradiation (ENI). We reviewed the evidence for ENI on a background of current practice among UK clinical oncologists.

Revised Modelling of the Addition of Synchronous Chemotherapy to Radiotherapy in Squamous Cell Carcinoma of the Head and Neck-A Low ?

The effect of synchronous chemotherapy in squamous cell carcinoma of the head and neck (SCCHN) has been modelled as additional Biologically Effective Dose (BED) or as a prolonged tumour cell turnover time during accelerated repopulation. Such models may not accurately predict the local control seen when hypofractionated accelerated radiotherapy is used with synchronous chemotherapy. For the purposes of this study three isoeffect relationships were assumed: Firstly, from the RTOG 0129 trial, synchronous cisplatin chemotherapy with 70 Gy in 35 fractions over 46 days results in equivalent local control to synchronous cisplatin chemotherapy with 36 Gy in 18# followed by 36 Gy in 24# (2# per day) over a total of 39 days.

Models of acute mucosal tolerance to radiotherapy alone applied to synchronous chemoradiation schedules in head and neck cancer.

Three models defining mucosal tolerance when radiotherapy alone is delivered have been published. Modelling studies have converted the contribution of synchronous chemotherapy to the rate of grade 3 mucositis to biologically effective dose (BED). The purpose of this study was to apply radiotherapy mucosal tolerance models to studies of synchronous chemoradiation.

Critical appraisal of axitinib in the treatment of advanced renal cell carcinoma.

A growing understanding of the biology of renal cell carcinoma (RCC) has led to the development and US Food and Drug Administration approval of seven new molecular targeted agents over the past 7 years. Axitinib is a potent, selective, second-generation inhibitor of vascular endothelial growth factor receptors and the latest to join the armamentarium of drugs available for the treatment of metastatic RCC. Despite recent advances in the development of molecular targeted agents for metastatic RCC, the ideal sequencing of these agents remains unclear.

Revising the radiobiological model of synchronous chemotherapy in head-and-neck cancer: a new analysis examining reduced weighting of accelerated repopulation.

Purpose: Previous studies of synchronous chemoradiation therapy have modeled the additional effect of chemotherapy as additional radiation therapy biologically effective dose (BED). Recent trials of accelerated versus conventional fractionation chemoradiation have cast doubt on such modeling. The purpose of this study was to identify alternative models.

Can radiobiological parameters derived from squamous cell carcinoma of the head and neck be used to predict local control in anal cancer treated with chemoradiation?

Objectives: Parameters have been derived in head and neck cancer to account for the additional biological effective dose provided by synchronous chemotherapy. The purpose of this study was to establish whether such parameters could be used to predict local control differences in anal cancer.

Methods: In anal cancer two randomised trials of radiotherapy vs chemoradiotherapy and two trials randomising between different synchronous chemotherapy regimens were identified.

Pulmonary toxicity with oxaliplatin and capecitabine/5-Fluorouracil chemotherapy: a case report and review of the literature.

Background: Oxaliplatin in combination with either 5-fluorouracil or capecitabine is commonly used in the treatment of colorectal cancer and is rarely associated with pulmonary toxicity. This is the first reported case of oxaliplatin and capecitabine/5-fluorouracil causing pulmonary toxicity in a patient with pre-existing asymptomatic interstitial lung disease.

Case Report: We report a case of a man who was treated with oxaliplatin and capecitabine for 1 cycle, then subsequently with oxaliplatin and 5-fluorouracil following a resected Dukes' C colon carcinoma.

Role of second-line systemic treatment post-docetaxel in metastatic castrate resistant prostate cancer- current strategies and future directions.

Treatment of metastatic castrate resistant prostate cancer (mCRPC) after progression on docetaxel chemotherapy is a challenging clinical scenario with limited availability of treatment options. Re-treatment with docetaxel, either as monotherapy or in combination with other cytotoxics or targeted agents has shown durable responses. However, most docetaxel re-treatment studies have been either retrospective or early phase non-randomised studies which have not formally assessed Quality of life or survival gain with re-treatment.

Hypofractionated accelerated radiotherapy with concurrent carboplatin for locally advanced squamous cell carcinoma of the head and neck.

Aims: Hypofractionated accelerated radiotherapy with concurrent carboplatin utilises both advantages of altered fractionation and synchronous chemotherapy to maximise local control in locally advanced head and neck cancer. Such fractionation schedules are increasingly used in the intensity-modulated radiotherapy era and the aim of this study was to determine the outcome of hypofractionated accelerated radiotherapy with carboplatin.

Materials And Methods: One hundred and fifty consecutive patients with squamous cell carcinoma of the larynx, oropharynx, oral cavity and hypopharynx (International Union Against Cancer [IUAC] stage II-IV) treated with 55Gy in 20 fractions over 25 days with concurrent carboplatin were analysed.

Correlation of currently used radiobiological parameters with local control and acute and late mucosal toxicity in randomised studies of altered fractionation for locally advanced head and neck cancer.

Aims: There has been a resurgence in interest in radiobiological modelling in head and neck cancer. The aim of this study was to determine if currently used parameters accurately predict both tumour and toxicity outcomes.

Materials And Methods: Trials were identified from a recent meta-analysis of altered fractionation.

Recent advances and future directions in the management of metastatic renal cell carcinoma.

A better understanding of the molecular biology of renal cell carcinoma (RCC) and the emergence of tyrosine kinase inhibitors (TKIs) have revolutionized the treatment for patients with metastatic RCC (mRCC). Multikinase inhibitors (sunitinib and sorafenib) and the inhibitors of mammalian target of rapamycin (temsirolimus and everolimus) have recently shown superiority over IFN-alpha or placebo; and bevacizumab + IFN-alpha have demonstrated improved activity when compared to IFN-alpha alone in patients with mRCC. Newer anti-vascular endothelial growth factor (VEGF) agents such as axitinib, pazopanib and cediranib are currently under investigation to expand and elucidate future treatment options.

Can synchronous chemotherapy be added to accelerated hypofractionated radiotherapy in patients with base of tongue cancer?

Aim: To evaluate the tolerability of synchronous chemotherapy and accelerated hypofractionated radiotherapy in patients with locally advanced squamous cell carcinoma of the base of the tongue.

Materials And Methods: Between 1999 and 2004, 43 patients with stage II-IV squamous cell carcinoma of the base of the tongue were treated with a combined modality of radiotherapy (prescribed 55 Gy in 20 fractions), synchronous chemotherapy and in some cases surgical neck dissection. End points were acute and late toxicity, 3 year locoregional control, overall survival, cancer-specific survival and compliance.

Radiobiological modelling of the therapeutic ratio for the addition of synchronous chemotherapy to radiotherapy in locally advanced squamous cell carcinoma of the head and neck.

Aims: To model the therapeutic gain from the addition of synchronous chemotherapy to radiotherapy in locally advanced head and neck cancer.

Materials And Methods: Refinements to previous methodology, including the derivation of weighted estimates of key parameters from randomised studies and the use of the expected mucosal biologically effective dose concept, have been used to produce an evidence-based assessment of the benefit from the addition of chemotherapy when considering acute grade 3 mucositis and rates of 5-year local control.

Results: For a value of alpha=0.

Chemoradiotherapy for locally advanced head and neck cancer: 10-year follow-up of the UK Head and Neck (UKHAN1) trial.

Background: Between 1990 and 2000, we examined the effect of timing of non-platinum chemotherapy when combined with radiotherapy. We aimed to determine whether giving chemotherapy concurrently with radiotherapy or as maintenance therapy, or both, affected clinical outcome. Here we report survival and recurrence after 10 years of follow-up.

Outcome of T1N0M0 squamous cell carcinoma of the larynx treated with short-course radiotherapy to a total dose of 50 Gy in 16 fractions: the Birmingham experience.

Aims: To review the results of hypofractionated radiotherapy in T1N0M0 squamous cell carcinoma of the larynx.

Materials And Methods: A series of 100 patients treated with radiotherapy between 1993 and 2001 was reviewed. The median age was 67 years.

Docetaxel chemotherapy for metastatic hormone refractory prostate cancer as first-line palliative chemotherapy and subsequent re-treatment: Birmingham experience.

Three-weekly docetaxel chemotherapy with prednisolone is now considered standard of care for patients with metastatic hormone refractory prostate cancer (MHRPC). This study reports the efficacy and toxicity of first-line docetaxel chemotherapy followed subsequently by re-treatment on biochemical disease progression (BDP). Forty-two patients with MHRPC were treated with three-weekly docetaxel chemotherapy 75 mg/m(2) and 10 mg of prednisolone daily.

Oral sodium clodronate for nonmetastatic prostate cancer--results of a randomized double-blind placebo-controlled trial: Medical Research Council PR04 (ISRCTN61384873).

Background: The most frequent site of metastases from prostate cancer is bone. Adjuvant bisphosphonate treatment improves outcomes of patients with bone metastasis-negative breast cancer, but the effects of bisphosphonates on bone metastases in prostate cancer are not known.

Methods: We performed a randomized double-blind placebo-controlled trial to determine whether a first-generation bisphosphonate could improve symptomatic bone metastasis-free survival (time to symptomatic bone metastases or death from prostate cancer) in men with nonmetastatic prostate cancer who were at high risk of developing bone metastases.

Hypofractionated accelerated radiotherapy with concurrent chemotherapy for locally advanced squamous cell carcinoma of the head and neck.

Purpose: To investigate the tumor control rates in locally advanced head-and-neck cancer using accelerated hypofractionated radiotherapy with chemotherapy.

Methods And Materials: The data from patients with squamous cell cancer of the larynx, oropharynx, oral cavity, and hypopharynx (International Union Against Cancer Stage II-IV), who received accelerated hypofractionated radiotherapy with chemotherapy between January 1, 1998, and April 1, 2005, were retrospectively analyzed. Two different chemotherapy schedules were used, carboplatin and methotrexate, both single agents administered on an outpatient basis.

Carboplatin and hypofractionated accelerated radiotherapy: a dose escalation study of an outpatient chemoradiation schedule for squamous cell carcinoma of the head and neck.

Aim: To examine the feasibility and determine the maximum tolerated dose of outpatient carboplatin given with synchronous hypofractionated accelerated radiotherapy for squamous cell carcinoma of the head and neck (SCCHN).

Materials And Methods: Patients with stages II-IV SCCHN and unresected primary tumour were treated with synchronous carboplatin given in an outpatient setting on day 1 and day 21 in cohorts of three to six patients with incremental area under curve (AUC) factors commencing at 3.5.

The management of squamous cell carcinoma of the neck. The Birmingham UK experience.

Aims: To review our treatment strategy and outcomes for metastatic squamous cell carcinoma of the neck.

Methods: One hundred and six consecutive patients treated between 1992 and 1998 were analysed retrospectively. The following data were obtained.