Dyspnea in Patients Receiving Radical Radiotherapy for Non-Small Cell Lung Cancer: A Prospective Study.

BACKGROUND AND PURPOSE: Dyspnea is an important symptomatic endpoint for assessment of radiation-induced lung injury (RILI) following radical radiotherapy in locally advanced disease, which remains the mainstay of treatment at the time of significant advances in therapy including combination treatments with immunotherapy and chemotherapy and the use of local ablative radiotherapy techniques. We investigated the relationship between dose-volume parameters and subjective changes in dyspnea as a measure of RILI and the relationship to spirometry. MATERIAL AND METHODS: Eighty patients receiving radical radiotherapy for non-small cell lung cancer were prospectively assessed for dyspnea using two patient-completed tools: EORTC QLQ-LC13 dyspnea quality of life assessment and dyspnea visual analogue scale (VAS). Global quality of life, spirometry and radiation pneumonitis grade were also assessed. Comparisons were made with lung dose-volume parameters. RESULTS: The median survival of the cohort was 26 months. In the evaluable group of 59 patients there were positive correlations between lung dose-volume parameters and a change in dyspnea quality of life scale at 3 months (V30 p=0.017; V40 p=0.026; V50 p=0.049; mean lung dose p=0.05), and a change in dyspnea VAS at 6 months (V30 p=0.05; V40 p=0.026; V50 p=0.028) after radiotherapy. Lung dose-volume parameters predicted a 10% increase in dyspnea quality of life score at 3 months (V40; p=0.041, V50; p=0.037) and dyspnea VAS score at 6 months (V40; p=0.027) post-treatment. CONCLUSIONS: Worsening of dyspnea is an important symptom of RILI. We demonstrate a relationship between lung dose-volume parameters and a 10% worsening of subjective dyspnea scores. Our findings support the use of subjective dyspnea tools in future studies on radiation-induced lung toxicity, particularly at doses below conventional lung radiation tolerance limits.

Baseline and post prophylactic tubal-ovarian surgery CA125 levels in BRCA1 and BRCA2 mutation carriers.

The aim of this study was to determine whether BRCA1 and BRCA2 mutation carriers have different baseline CA125 levels compared with non-carriers, and whether a significant difference in pre- and post-operative CA125 levels exists in BRCA mutation carriers undergoing risk-reducing bilateral salpingo-oophorectomy (RRBSO). The study also considered whether CA125 measurements should continue in unaffected BRCA mutation carriers after RRBSO. 383 Eligible women were identified through retrospective review of the BRCA Carrier Clinic at The Royal Marsden NHS Foundation Trust, London, UK. These women all had CA125 levels measured as they were either a carrier or at risk of a BRCA1 or BRCA2 mutation. Of these, 76 went on to have a negative predictive test for their familial mutation and so are classed as 'non-carriers'. 133 BRCA1 and 87 BRCA2 carriers had RRBSO, with a further 26 BRCA1 carriers, 28 BRCA2 carriers and one non-carrier developing ovarian cancer. The remaining 21 BRCA1 and 28 BRCA2 carriers did not have RRBSO or develop ovarian cancer in the time of study follow-up. CA125 levels were measured as surveillance or as part of pre-RRBSO care. CA125 measurement post-RRBSO was continued in 48 BRCA1 and 40 BRCA2 carriers. In 154 BRCA1 mutation carriers, the median baseline (i.e. before RRBSO and with no clinical signs of ovarian cancer) CA125 level was 9.0 U/ml (range 2-78) and was 10.0 U/ml (range 1-43) in 115 BRCA2 mutation carriers. When compared with the 75 non-carriers (median baseline CA125 10.0 U/ml; range 2-52), there was no significant difference between the BRCA1, BRCA2 and non-carrier groups. There was a significant reduction in CA125 from pre- to post-RRBSO in 48 BRCA1 carriers (p = 0.04) but no significant difference in 40 BRCA2 mutation carriers (p = 0.5). Out of a total of 220 mutation carriers who underwent RRBSO, two had an incidental ovarian cancer found on histopathology and another developed primary peritoneal cancer during the follow-up period. Our study is the first to compare initial serum CA125 levels in BRCA1 and BRCA2 mutation carriers with those of non-carriers. Our study found no significant difference between the three groups. A drop in CA125 levels after RRBSO in BRCA1 carriers supports the finding of earlier studies, but differed in that the fall was not seen in BRCA2 carriers. The finding of only one case of post-operative peritoneal cancer in 220 carriers undergoing RRBSO supports the discontinuation of post-RRBSO serum CA125 monitoring in BRCA mutation carriers.

Long-term efficacy of fractionated radiotherapy for benign meningiomas.

PURPOSE: To assess long term efficacy of fractionated stereotactic radiotherapy (fSRT) in the treatment of benign intracranial meningiomas. MATERIALS AND METHODS: Retrospective study of 222 patients with histologically confirmed (58%) and unverified presumed (42%) grade I intracranial meningioma treated with fSRT in a single institution to doses of 50-55Gy in 30-33 fractions. RESULTS: At a median follow-up of 43months (range 3-144) the 5 and 10years local control (LC) were 93% and 86%. Patients with tumors involving the optic nerve (42 patients) and patients with cavernous sinus/parasellar region meningiomas (78 patients) had 5 and 10years LC of 100%. The 5 and 10years survival probabilities were 93% and 84%. On multivariate analysis gender and tumor site were independent predictors of LC. Worsening of pre-existing cranial nerve deficit occurred in 8 (3.5%) and onset of new deficit in 1 (0.5%) patient. Two patients with optic nerve sheath meningioma (1%) developed radiation retinopathy. There were no cases of radiation necrosis or second brain tumors. CONCLUSION: fSRT achieves excellent medium and long term tumor control with minimal morbidity particularly in patients with benign meningiomas involving the parasellar region and the optic nerves and questions the role of other treatment modalities for tumors at these locations.

Stereotactic radiotherapy (SABR) for the treatment of primary non-small cell lung cancer; systematic review and comparison with a surgical cohort.

BACKGROUND AND PURPOSE: To assess the efficacy of stereotactic ablative radiotherapy (SABR) for the treatment of non-small cell lung cancer (NSCLC) through a systematic review of all relevant publications from 2006 to the present compared to controls treated with surgery. In the absence of Grade I evidence, the objective outcome data should form the basis for planning future studies and commissioning SABR services. MATERIALS AND METHODS: Standard systematic review methodology extracting patient and disease characteristics, treatment and outcome data from published articles reporting patient data from populations of 20 or more Stage I NSCLC patients treated with SABR with a median follow up of minimum of 1 year. The individual outcome measures were corrected for stage and summary weighted outcome data were compared to outcome data from a large International Association for the Study of Lung Cancer (IASLC) cohort matched for stage of disease with survival as the principal endpoint and local control (local progression free survival - local PFS) as the secondary endpoint. RESULTS: Forty-five reports containing 3771 patients treated with SABR for NSCLC were identified that fulfilled the selection criteria; both survival and staging data were reported in 3171 patients. The 2 year survival of the 3201 patients with localized stage I NSCLC treated with SABR was 70% (95% CI: 67-72%) with a 2 year local control of 91% (95% CI: 90-93%). This was compared to a 68% (95% CI: 66-70) 2 year survival of 2038 stage I patients treated with surgery. There was no survival or local PFS difference with different radiotherapy technologies used for SABR. CONCLUSIONS: Systematic review of a large cohort of patients with stage I NSCLC treated with SABR suggests that survival outcome in the short and medium term is equivalent to surgery for this population of patients regardless of co-morbidity. As selection bias cannot be assessed from the published reports and treatment related morbidity data are limited, a direct comparison between the two treatment approaches should be a priority. In the meantime, SABR can be offered to stage I patients with NSCLC as an alternative to surgery.

Comparison of setup accuracy and intrafraction motion using stereotactic frame versus 3-point thermoplastic mask-based immobilization for fractionated cranial image guided radiation therapy.

PURPOSE: Prospectively compare patient setup accuracy and intrafraction motion of a standard 3-point thermoplastic mask with the Gill-Thomas-Cosman relocatable stereotactic frame, during fractionated cranial radiation therapy using the ExacTrac system (Brainlab AG Feldkirchen, Germany) for daily online correction. METHODS AND MATERIALS: The number of fractions with all postcorrection and post-treatment errors <2 mm was assessed in 21 patients undergoing fractionated stereotactic radiation therapy (13 frame setup, 8 mask setup) using daily online correction. Achievable patient setup accuracy and total intrafraction motion were evaluated. The relative contributions of movement during floor rotation and patient movement to intrafraction motion were calculated. RESULTS: With daily online correction, patient setup margins can be reduced from 1, 5, and 4 mm in the lateral, longitudinal, and vertical axes for mask setup and from 1-2, 2, and 1 mm, respectively, for frame setup to <1 mm isotropically for either immobilization system. Intrafraction movement was small for frame setup (mean [SD], -0.3 [0.3], -1.1[0.4], and -0.2 [0.6] in lateral, longitudinal and vertical axes, respectively; maximum, -2.7 mm [longitudinal axis]), and mask-setup (mean [SD], -0.4 [0.5], -0.8 [0.7], and 0.0 [0.3], respectively; maximum, -2.0 mm [longitudinal axis]) and is mainly due to floor rotation. Postcorrection and post-treatment errors were all <2 mm in 95% and 99% of fractions in the mask and frame, respectively, meeting the criteria for a 3-mm clinical target volume-planning target volume margin for either immobilization method. CONCLUSIONS: Daily online correction can compensate for less precise immobilization and permits stereotactic margins to be used for standard thermoplastic masks without the need for specialized mask systems.

Assessment of gemcitabine, cisplatin and methylprednisolone (GEM-P) combination treatment for non-Hodgkin T cell lymphoma.

T cell lymphoma is rare with few dedicated studies and no consensus regarding optimal treatment. We undertook a retrospective hospital review to assess the efficacy of gemcitabine, cisplatin and methylprednisolone (GEM-P) combination therapy. Twenty-nine patients were followed up for a median duration of 28 months. Twenty-three patients received standard GEM-P. Due to hearing impairment, 3 patients had cisplatin substituted with carboplatin and 1 with oxaliplatin. In 2 cases, rituximab was added to GEM-P in view of the presence of EBV + B cell clones. Overall response rate (RR) [complete response (CR) + partial response (PR)] was 73 % (95 % CI range 54-86 %). 11/29 (38 %) achieved CR and 10/29 (35 %) had PR. In first-line treatment, 4/10 patients achieved CR and 4/10 had PR relating to a RR of 80 %. CR was seen in 4/9 (45 %), 2/8 (25) and 1/2 (50 %) patients treated in the second, third and fifth-sixth line respectively. Thus, GEM-P was found to be effective as first-line or salvage therapy in T cell lymphoma.

Establishing an EGFR mutation screening service for non-small cell lung cancer - sample quality criteria and candidate histological predictors.

INTRODUCTION: EGFR screening requires good quality tissue, sensitivity and turn-around time (TAT). We report our experience of routine screening, describing sample type, TAT, specimen quality (cellularity and DNA yield), histopathological description, mutation result and clinical outcome. METHODS: Non-small cell lung cancer (NSCLC) sections were screened for EGFR mutations (M+) in exons 18-21. Clinical, pathological and screening outcome data were collected for year 1 of testing. Screening outcome alone was collected for year 2. RESULTS: In year 1, 152 samples were tested, most (72%) were diagnostic. TAT was 4.9 days (95%confidence interval (CI)=4.5-5.5). EGFR-M+ prevalence was 11% and higher (20%) among never-smoking women with adenocarcinomas (ADCs), but 30% of mutations occurred in current/ex-smoking men. EGFR-M+ tumours were non-mucinous ADCs and 100% thyroid transcription factor (TTF1+). No mutations were detected in poorly differentiated NSCLC-not otherwise specified (NOS). There was a trend for improved overall survival (OS) among EGFR-M+ versus EGFR-M- patients (median OS=78 versus 17 months). In year 1, test failure rate was 19%, and associated with scant cellularity and low DNA concentrations. However 75% of samples with poor cellularity but representative of tumour were informative and mutation prevalence was 9%. In year 2, 755 samples were tested; mutation prevalence was 13% and test failure only 5.4%. Although samples with low DNA concentration (<2 ng/µL) had more test failures (30% versus 3.9% for [DNA]>2.2 ng/µL), the mutation rate was 9.2%. CONCLUSION: Routine epidermal growth factor receptor (EGFR) screening using diagnostic samples is fast and feasible even on samples with poor cellularity and DNA content. Mutations tend to occur in better-differentiated non-mucinous TTF1+ ADCs. Whether these histological criteria may be useful to select patients for EGFR testing merits further investigation.

Somnolence syndrome in patients receiving radical radiotherapy for primary brain tumours: a prospective study.

BACKGROUND AND PURPOSE: To characterise the incidence, pattern and severity of post cranial radiotherapy somnolence and to identify factors predictive of frequency and severity. MATERIALS AND METHODS: Seventy consecutive patients receiving radical cranial irradiation were prospectively assessed for somnolence at baseline, during and up to 10weeks following radiotherapy using five variables scored on a visual analogue scale (VAS) and the Littman scale. Fatigue was measured using the FACT-G score and quality of life using the EORTC QLQC30+3 with the brain tumour module questionnaire. RESULTS: Ninety percent of patients experienced ⩾grade 1 somnolence (Littman score) and this correlated with VAS scores (r=0.456, p<0.001). The score increased from 3 to 12weeks (p<0.001) with a peak at the end of treatment and improvement 6weeks later. None of the patient, disease or treatment characteristics analysed were predictive for the development or the severity of somnolence. CONCLUSIONS: The majority of patients experience some degree of somnolence following radical radiotherapy for primary brain tumour and this follows a clear pattern during and after treatment. While there are no clear predictors of severity, the pattern described allows for provision of information for patients and carers to minimise the distress the syndrome may cause.

The role of ipsilateral breast radiotherapy in management of occult primary breast cancer presenting as axillary lymphadenopathy.

AIM: To assess the role of ipsilateral breast radiotherapy (IBR) in women with occult primary breast cancer presenting with axillary metastases (OPBC). METHODS: Patients with axillary nodal metastases and histological diagnosis of breast cancer without palpable, mammographic or ultrasonographic evidence of a breast primary were identified from a prospectively maintained single institution database. Imaging, surgery, radiotherapy, recurrence and survival data were collected. Patients whose breast cancer primary was detected on MRI (but occult on clinical examination and other imaging) were excluded from the analyses of IBR and outcome, but were included in other exploratory analyses. RESULTS: Fifty-five patients were included between 1975 and 2009. Median follow up was 68 months. Twenty patients had breast magnetic resonance imaging (MRI) in addition to other imaging. A primary breast cancer was detected in 7 of these 20. 48/55 patients had no detectable breast primary. 35/48 patients (73%) were treated with radiotherapy to the conserved breast, and 13/48 (27%) with observation. Patients who had IBR had better 5 year local recurrence free survival (LRFS) (84% versus 34%, p<0.001), and relapse free survival (RFS) (64% versus 34%, p=0.05), but no difference in overall survival (OS) (84% versus 85%, p=0.2). There was no difference in 5 year LRFS (80% versus 90%: p=0.3) between patients who received radiation of 50 Gy in 25 fractions versus ≥60 Gy. CONCLUSION: Patients with OPBC should be managed with IBR and breast conservation, or mastectomy. Our data suggest it is not necessary to irradiate the breast to more than 50 Gy in 25 fractions.

Docetaxel and irinotecan as second-line therapy for advanced oesophagogastric cancer.

INTRODUCTION: Systemic chemotherapy improves survival in oesophagogastric cancer however no standard second-line regimen exists due to a paucity of randomised data. Docetaxel combined with irinotecan (DI) provides a suitable option due to the lack of cross-reactivity with first-line therapeutics and a tolerable toxicity profile. METHODS: We retrospectively reviewed a cohort of patients with advanced oesophagogastric cancer in two institutions treated with the combination of docetaxel 35 mg/m(2) plus irinotecan 60 mg/m(2) day 1 and day 8 every 21 days, following progression with first-line platinum-based therapy. RESULTS: Between January 2000 and September 2009, 41 eligible patients were identified. Median age was 58 years, male:female 25:16, adenocarcinoma:squamous cell carcinoma 37:4, oesophageal:oesophagogastric junction:gastric 7:10:24. Locally advanced:metastatic disease 6:35. Previous radical surgery:radiotherapy:both 6:4:7. 27/41 had progressed within 90 days of receiving platinum-based therapy. Median number of chemotherapy cycles: 3 (range 1-12). Eight patients required dose reductions due to DI toxicity. 10/28 evaluable patients had a response, median progression-free survival (PFS) was 11 weeks (95% confidence intervals (CI): 9-13 weeks) with median overall survival 24 weeks (95%CI: 12-35 weeks). No significant prognostic factors were identified. CONCLUSION: Weekly docetaxel combined with irinotecan has acceptable safety and modest efficacy in the second-line treatment of advanced oesophagogastric cancer. Further prospective evaluation of this regimen is warranted.

Mixed-phenotype acute leukemia: clinical and laboratory features and outcome in 100 patients defined according to the WHO 2008 classification.

The features of 100 mixed-phenotype acute leukemias (MPALs), fulfilling WHO 2008 criteria, are documented. Myeloid and T-lineage features were demonstrated by cytoplasmic myeloperoxidase and CD3; B-lineage features were demonstrated by at least 2 B-lymphoid markers. There were 62 men and 38 women; 68% were adults. Morphology was consistent with acute lymphoblastic leukemia (ALL; 43%), acute myeloid leukemia (AML; 42%), or inconclusive (15%). Immunophenotyping disclosed B + myeloid (59%), T + myeloid (35%), B + T (4%), or trilineage (2%) combinations. Cytogenetics evidenced t(9;22)/(Ph(+)) (20%), 11q23/MLL rearrangements (8%), complex (32%), aberrant (27%), or normal (13%) karyotypes. There was no correlation between age, morphology, immunophenotype, or cytogenetics. Response to treatment and outcome were available for 67 and 70 patients, respectively; 27 received ALL, 34 AML, 5 a combination of ALL + AML therapy, and 1 imatinib. ALL treatment induced a response in 85%, AML therapy in 41%; 3 of 5 patients responded to the combination therapy. Forty (58%) patients died, 33 of resistant disease. Overall median survival was 18 months and 37% of patients are alive at 5 years. Age, Ph(+), and AML therapy were predictors for poor outcome (P < .001; P = .002; P = .003). MPAL is confirmed to be a poor-risk disease. Adults and Ph(+) patients should be considered for transplantation in first remission.

Chemotherapy in clear cell sarcoma.

Clear cell sarcoma is a rare translocation-related sarcoma. There have been few studies documenting the response rate and progression-free survival in clear cell sarcoma patients treated with palliative chemotherapy. The prospectively maintained databases of two referral centres were searched to identify clear cell sarcoma patients treated with chemotherapy. Twenty-four patients were treated with palliative first-line chemotherapy with a median age of 30 years at diagnosis. There were 18 men and 6 women. One (4%) achieved a partial response and 9 (38%) had stable disease. Fourteen patients (58%) progressed on therapy. The median progression-free survival was 11 weeks (95% CI, 3­20 weeks). The median overall survival from commencing first-line chemotherapy was 39 weeks (95% CI, 34­45 weeks). Second-line chemotherapy was administered to 12 patients, 11 (92%) of these progressed and one (8%) had stable disease. Of the 5 patients treated with third-line chemotherapy, 4 (80%) progressed and one (20%) had stable disease. One patient received fourth-line chemotherapy and maintained stable disease for 4 months. Conventional chemotherapy has minimal activity in clear cell sarcoma as documented by the response rate of 4% and median progression-free survival of 11 weeks in this retrospective series. These data provide a reference for response and outcome in the assessment of novel agents in this histological subtype.

Fractionated stereotactic radiotherapy in the treatment of vestibular schwannoma (acoustic neuroma): predicting the risk of hydrocephalus.

PURPOSE: To determine the incidence and predictive factors for the development of hydrocephalus in patients with acoustic neuromas (AN) treated with fractionated stereotactic radiotherapy. PATIENTS AND METHODS: Seventy-two patients with AN were treated with fractionated stereotactic radiotherapy between 1998 and 2007 (45-50 Gy in 25-30 fractions over 5 to 6 weeks). The pretreatment MRI scan was assessed for tumor characteristics and anatomic distortion independently of subsequent outcome and correlated with the risk of hydrocephalus. RESULTS: At a median follow-up of 49 months (range, 1-120 months), 5-year event-free survival was 95%. Eight patients (11%) developed hydrocephalus within 19 months of radiotherapy, which was successfully treated. On univariate analysis, pretreatment factors predictive of hydrocephalus were maximum diameter (p = 0.005), proximity to midline (p = 0.009), displacement of the fourth ventricle (p = 0.02), partial effacement of the fourth ventricle (p < 0.001), contact with the medulla (p = 0.005), and more brainstem structures (p = 0.004). On multivariate analysis, after adjusting for fourth ventricular effacement, no other variables remained independently associated with hydrocephalus formation. CONCLUSIONS: Fractionated stereotactic radiotherapy results in excellent tumor control of AN, albeit with a risk of developing hydrocephalus. Patients at high risk, identified as those with larger tumors with partial effacement of the fourth ventricle before treatment, should be monitored more closely during follow-up. It would also be preferable to offer treatment to patients with progressive AN while the risk of hydrocephalus is low, before the development of marked distortion of fourth ventricle before tumor diameter significantly exceeds 2 cm.

Serum angiogenic profile of patients with glioblastoma identifies distinct tumor subtypes and shows that TIMP-1 is a prognostic factor.

Angiogenesis plays a key role in glioblastoma biology and antiangiogenic agents are under clinical investigation with promising results. However, the angiogenic profiles of patients with glioblastoma and their clinical significance are not well understood. Here we characterize the serum angiogenic profile of patients with glioblastoma, and examine the prognostic significance of individual angiogenic factors. Serum samples from 36 patients with glioblastoma were collected on admission and simultaneously assayed for 48 angiogenic factors using protein microarrays. The data were analyzed using hierarchical cluster analysis. Vessel morphology was assessed histologically after immunostaining for the pan-endothelial marker CD31. Tumor samples were also immunostained for tissue inhibitor of metalloproteinase-1 (TIMP-1). Cluster analysis of the serum angiogenic profiles revealed 2 distinct subtypes of glioblastoma. The 2 subtypes had markedly different tumor microvessel densities. A low serum level of TIMP-1 was associated with significantly longer survival independent of patient age, performance status, or treatment. The serum angiogenic profile in patients with glioblastoma mirrors tumor biology and has prognostic value. Our data suggest the serum TIMP-1 level as an independent predictor of survival.

Epirubicin, oxaliplatin, and capecitabine with or without panitumumab for advanced esophagogastric cancer: dose-finding study for the prospective multicenter, randomized, phase II/III REAL-3 trial.

PURPOSE: Epirubicin, oxaliplatin, and capecitabine (EOC) is a standard treatment in advanced esophagogastric cancer. Panitumumab (P) is a fully human, immunoglobulin G2 monoclonal antibody targeting epidermal growth factor receptor. Randomized Trial of EOC +/- Panitumumab for Advanced and Locally Advanced Esophagogastric Cancer (REAL-3) will evaluate whether the addition of P to EOC improves survival in patients with advanced esophagogastric adenocarcinoma and undifferentiated carcinoma. PATIENTS AND METHODS: The original design of REAL-3 added P 9 mg/kg to the standard dose of EOC (dose level [DL] + 1). Due to toxicity, a dose de-escalation was made to EOC + P DL-1 (epirubicin 50 mg/m(2), oxaliplatin130 mg/m(2), capecitabine 1,000 mg/m(2)/d + P 9 mg/kg every 3 weeks). After additional toxicity was observed, the study was amended to include two additional EOC + P dose levels. Using a 3 + 3 design, dose-limiting toxicities (DLTs) were assessed weekly during cycle 1. Patients were randomly assigned 1:1 to EOC +/- P. RESULTS: Between July 2008 and October 2009, 29 patients were randomly selected for standard-dose EOC (n = 13) or EOC + P (n = 16). Five patients were treated at DL + 1, with grade 3 diarrhea in four of five patients by cycle 4. At DL-1, one patient had grade 3 diarrhea and grade 5 infection. Three patients were treated at DL-3, and then six were treated at DL-2, without DLTs. CONCLUSION: The recommended dose for EOC + P is epirubicin 50 mg/m(2), oxaliplatin 100 mg/m(2), capecitabine 1,000 mg/m(2)/d, and P 9 mg/kg every 3 weeks. This dose has been selected for the ongoing phase II/III REAL-3 study.

Thirty-day mortality in critical care outreach patients with cancer: an investigative study of predictive factors related to outreach referral episodes.

AIM: To establish factors that predict outcome in critically ill, deteriorating cancer patients through critical care outreach referral episodes, characteristics and care reviews. METHODS: A population-based prospective and retrospective study was undertaken with analysis exploring predictive factors regarding critically ill cancer patients referred to a critical care outreach team. Data collected included: diagnosis; presenting problem; early warning scores at referral and at deterioration; physiological and observation data; admission to critical care, length of stay; 30-day mortality; limitation of care including precipitating DNAR orders and documentation of not for CCU admission/intervention). RESULTS: Data were collected on 407 episodes from 318 patients over a period of 8 months from 2006 to 2007. Outreach initiated decisions to limit care with medical teams in 32.2% (n=103/318) of all patients. Early warning scores were not predictive of outcome. A high heart rate at referral (HR), a high potassium, low SpO2 at time of deterioration were independently predictive of 30-day mortality. The logistic regression (LR) model, using these three variables correctly predicts the 30-day outcome of 71% of the patients, demonstrating a relatively high predictability in this patient population. The odds of mortality increase with a higher potassium, heart rate and as the oxygen saturation at deterioration (DSpO(2)) worsen. Management factors included limitation of care, which is highly associated with 30-day mortality. Cancer patients recently receiving chemotherapy may have an increased mortality once admitted to critical care. Being a haemato-oncology patient, or the timeliness of critical care outreach referral does not appear to affect 30-day mortality. CONCLUSION: The LR model was able to predict 30-day outcome of 71% of the patients, demonstrating a reasonably high predictability in this cancer patient population. Critical care outreach initiated discussions on limiting treatment which had an effect on mortality.

Modest reductions in dose intensity and drug-induced neutropenia have no major impact on survival of patients with non-small cell lung cancer treated with platinum-doublet chemotherapy.

BACKGROUND: Previous studies investigating the effect of increased dose intensity and chemotherapy-induced neutropenia in patients with advanced non-small cell lung cancer (NSCLC) have not consistently shown significant survival benefits. METHODS: This retrospective analysis reviewed the outcome of patients receiving palliative chemotherapy for advanced NSCLC (stages III-IV) at the Royal Marsden Hospital. Regimens included cisplatin or carboplatin with either vinorelbine or gemcitabine on days 1 and 8, every 21 days. Patients who received at least four cycles of chemotherapy were classified into groups based on dose intensity, dose reductions, and worst grade of neutropenia for a landmark analysis. Comparisons between these groups for time to progression and overall survival were made by standard univariate and multivariate methods. RESULTS: One hundred sixty-nine of a total of 190 patients who received more than four cycles of chemotherapy during the period between November 1998 and December 2008 were included. One hundred twenty-five (73.9%) patients received four chemotherapy cycles with the remaining receiving up to six cycles. The median relative dose intensity for platinum was 93.9% (62.1-102%) and for vinorelbine/gemcitabine was 91.7% (37.8-105%). Dose reductions were recorded in 64 patients (37.8%), and 65 patients (38.5%) had grades 3 to 4 neutropenia. There were no statistically significant differences in time to progression and overall survival between any of the subgroups. CONCLUSIONS: This retrospective analysis demonstrates no significant relationship between survival and dose intensity (<90%), modest dose reductions (<20%), or chemotherapy-induced neutropenia in patients receiving standard doublet platinum containing chemotherapy in NSCLC.

Clinical benefit of second-line palliative chemotherapy in advanced soft-tissue sarcoma.

Background. This paper aimed to assess the utility of second-line chemotherapy in patients with advanced soft-tissue sarcoma. Materials and Methods. A retrospective search of a prospectively maintained database identified patients treated between 1991 and 2005. Patients with gastrointestinal stromal tumours, small round cell tumours, and Ewing's sarcoma were excluded. Response was assessed using WHO and RECIST. Patients who achieved stable disease for 6 months or more were classified as having disease control. Results. Three hundred and seventy-nine patients received second-line chemotherapy. Eighty-six (22.7%) achieved disease control. Median duration of response was 11 months (95% CI: 9-13). On multivariate analysis, pathological subtype, absence of lung metastases, and the use of combination chemotherapy were independent predictors of disease control. Twenty-eight (16.1%) patients who failed to respond to first-line therapy achieved disease control. Eight (2.1%) patients had sufficient downstaging to enable complete surgical resection. Progression-free survival was 23% at 6 months. Median overall survival was 8 months (95% CI: 7-10 months). On multivariate analysis, synovial histology and absence of lung metastases were associated with improved survival. Conclusion. Second-line chemotherapy can provide clinical benefit in over 20% of soft-tissue sarcoma patients.

Inflammatory breast cancer--The Royal Marsden Hospital experience: a review of 155 patients treated from 1990 to 2007.

BACKGROUND: Treatments for inflammatory breast cancer (IBC) have changed over the last 15 to 20 years. The authors of this report undertook a retrospective review of patients who were treated at the Royal Marsden Hospital (RMH) to determine whether recurrence-free survival (RFS) and overall survival (OS) have improved as treatment regimens have altered. METHODS: Detailed clinical-pathologic data were collected on patients who were treated for primary IBC at RMH between 1990 and 2007. A Cox regression model was used to investigate the factors that influenced OS. RESULTS: The median OS was 3 years and 4 months, and the median RFS was 1 year and 10 months. RFS was better in patients who had received taxane-containing regimens; however, there was no OS benefit. A pathologic complete response (pCR) was observed in 13 of 89 patients (15%), and those who achieved a pCR had significantly better RFS but no improvement in OS. The type of chemotherapy did not affect the pCR rate. One hundred thirty of 155 patients received radiotherapy, and those who did not receive radiotherapy had significantly worse outcomes. A multivariate Cox regression analysis indicated that the date of diagnosis, estrogen receptor (ER) status, and the presence of metastatic disease at diagnosis were significant prognostic factors. Patients who were diagnosed during or after 2000 had a relative risk of mortality of 0.5 compared with patients who were diagnosed before 2000. ER-positive patients had a median OS of 4.5 years and a median of RFS of 2.6 years versus 2.9 years and 1.4 years, respectively, for ER-negative patients. Patients who had metastatic disease at presentation had an OS of 1.7 years versus 3.9 years for those without metastatic disease at presentation. CONCLUSIONS: Achieving a pCR improved RFS but had no impact on OS. Patients who had metastatic disease at the outset fared much worse, and positive ER status conferred a better outlook.