Assessment of inter-centre agreement across multidisciplinary team meetings for patients with retroperitoneal sarcoma.

BACKGROUND: Decision-making in the management of patients with retroperitoneal sarcoma is complex and requires input from a number of different specialists. The aim of this study was to evaluate the levels of agreement in terms of resectability, treatment allocation, and organs proposed to be resected across different retroperitoneal sarcoma multidisciplinary team meetings. METHODS: The CT scans and clinical information of 21 anonymized retroperitoneal sarcoma patients were sent to all of the retroperitoneal sarcoma multidisciplinary team meetings in Great Britain, which were asked to give an opinion about resectability, treatment allocation, and organs proposed to be resected. The main outcome was inter-centre reliability, which was quantified using overall agreement, as well as the chance-corrected Krippendorff's alpha statistic. Based on the latter, the level of agreement was classified as: 'slight' (0.00-0.20), 'fair' (0.21-0.40), 'moderate' (0.41-0.60), 'substantial' (0.61-0.80), or 'near-perfect' (>0.80). RESULTS: Twenty-one patients were reviewed at 12 retroperitoneal sarcoma multidisciplinary team meetings, giving a total of 252 assessments for analysis. Consistency between centres was only 'slight' to 'fair', with rates of overall agreement and Krippendorff's alpha statistics of 85.4 per cent (211 of 247) and 0.37 (95 per cent c.i. 0.11 to 0.57) for resectability; 80.4 per cent (201 of 250) and 0.39 (95 per cent c.i. 0.33 to 0.45) for treatment allocation; and 53.0 per cent (131 of 247) and 0.20 (95 per cent c.i. 0.17 to 0.23) for the organs proposed to be resected. Depending on the centre that they had attended, 12 of 21 patients could either have been deemed resectable or unresectable, and 10 of 21 could have received either potentially curative or palliative treatment. CONCLUSIONS: Inter-centre agreement between retroperitoneal sarcoma multidisciplinary team meetings was low. Multidisciplinary team meetings may not provide the same standard of care for patients with retroperitoneal sarcoma across Great Britain.

Liposarcoma subtype recurrence and survival: A UK regional cohort study.

BACKGROUND: Clinical outcome data in the United Kingdom, Europe, and the United States have yet to facilitate appropriately specific surveillance for liposarcoma histological subtypes, despite being one of the most common soft tissue sarcomas. Therefore, this study aims to demonstrate histologic-specific differences in liposarcoma recurrence, disease progression, and survival and discuss the implications. METHODS AND FINDINGS: This cohort study involves patients from a regional sarcoma service in the UK who have had a primary surgical excision of liposarcoma between October 2002 and September 2019. The median follow-up is five years. Confirmed histopathological diagnoses of liposarcoma (n = 193) are organised according to the World Health Organisation recognised subtypes: atypical lipomatous tumours (ALT), myxoid, pleomorphic, and dedifferentiated liposarcomas. In addition, retroperitoneal variants (n = 34) are included to illustrate the broader spectrum of phenotypes. The primary outcomes were local recurrence, distant disease progression, and disease-specific death, and compared using Kaplan-Meier analyses and tumour variables using Cox proportional hazard analyses. All three primary outcomes significantly differed (P < 0.0001, n = 193). There were no metastases or disease-specific death in patients with ALT (n = 92) and no metastases of their retroperitoneal counterparts (n = 17). Amongst the metastasising cases of rarer subtypes, there were pulmonary spread of pleomorphic (8/9, n = 20), dedifferentiated (4/5, n = 18), and myxoid (2/3, n = 29) liposarcomas. CONCLUSION: An absence of metastases of ALT should be considered alongside global evidence. Surveillance protocols could better differentiate between these subtypes and, in doing so, save patients a considerable amount of irradiation, time, fear, and anxiety.

PET/CT of breast cancer regional nodal recurrences: an evaluation of contouring atlases.

BACKGROUND: To validate the Radiation Therapy Oncology Group (RTOG) and European Society for Radiotherapy and Oncology (ESTRO) breast cancer nodal clinical target volumes (CTVs) and to investigate the Radiotherapy Comparative Effectiveness Consortium (RADCOMP) Posterior Neck volume in relation to regional nodal recurrences (RNR). METHODS: From a population-based database, 69 patients were identified who developed RNR after curative treatment for breast cancer. RNRs were detected with 18-fluorodeoxyglucose-positron emission tomography-computed tomography (PET/CT). All patients were treatment-naïve for RNR when imaged. The RTOG and ESTRO nodal CTVs and RADCOMP Posterior Neck volumes were contoured onto a template patient's CT. RNRs were contoured on each PET/CT and deformed onto the template patient's CT. Each RNR was represented by a 5 mm diameter epicentre, and categorized as 'inside', 'marginal' or 'outside' the CTV boundaries. RESULTS: Sixty-nine patients with 226 nodes (median 2, range 1-11) were eligible for inclusion. Thirty patients had received adjuvant tangent and regional nodal radiotherapy, 16 tangent-only radiotherapy and 23 no adjuvant radiotherapy. For the RTOG CTVs, the RNR epicentres were 70% (158/226) inside, 4% (8/226) marginal and 27% (60/226) outside. They included the full extent of the RNR epicentres in 38% (26/69) of patients. Addition of the RADCOMP Posterior Neck volume increased complete RNR coverage to 48% (33/69) of patients. For the ESTRO CTVs, the RNR epicentres were 73% (165/226) inside, 2% (4/226) marginal and 25% (57/226) outside. They included the full extent of the RNR epicentres in 57% (39/69) of patients. Addition of the RADCOMP Posterior Neck volume increased complete RNR coverage to 70% (48/69) of patients. CONCLUSIONS: The RTOG and ESTRO breast cancer nodal CTVs do not fully cover all potential areas of RNR, but the ESTRO nodal CTVs provided full coverage of all RNR epicentres in 19% more patients than the RTOG nodal CTVs. With addition of the RADCOMP Posterior Neck volume to the ESTRO CTVs, 70% of patients had full coverage of all RNR epicentres.

Secretory carcinoma of the major salivary gland: Provincial population-based analysis of clinical behavior and outcomes.

BACKGROUND: Our aim was to identify the number of cases of secretory carcinoma (SC) of the major salivary gland in a population-based cohort and review its clinical behavior with long-term follow-up. METHODS: All malignant salivary gland tumors (MSGTs) diagnosed between 1980 and 2014 were assessed for histological features compatible with SC and 140 were selected for further analysis. RESULTS: Twenty two new cases of SC were identified, 19 of which were originally classified as acinic cell carcinoma, and 3 as adenocarcinoma, not otherwise specified (NOS). Lymph node involvement was less common in SC tumors (5%) than in the control group (11%). Disease recurrence was seen less frequently in SC (9%) than the control group (20%). Mean disease-free survival was 192 months for SC compared with 162 months for controls (P = 0.15). CONCLUSION: The clinical course of SC is typically indolent with a low risk of relapse not significantly different from other low-grade MSGT.

Population-Based Study of Stereotactic Radiosurgery or Fractionated Stereotactic Radiation Therapy for Vestibular Schwannoma: Long-Term Outcomes and Toxicities.

PURPOSE: To examine long-term local control of vestibular schwannoma and side effects in patients treated with stereotactic radiosurgery (SRS) and fractionated stereotactic radiation therapy (SRT) in British Columbia. METHODS AND MATERIALS: From August 1998 to May 2009, 207 patients were treated with radiation therapy (RT) at British Columbia Cancer Agency. 136 (66%) received SRS, and 71 (34%) received SRT. Dose prescriptions were 50 Gy/25 fractions for SRT and 12 Gy/1 fraction for SRS. Our multidisciplinary provincial neuro-stereotactic conference recommended SRT for tumors >3 cm and for patients with serviceable hearing (Gardner-Robertson classes I and II). RESULTS: Median follow-up was 7.7 years to the last MRI and 6.4 years to the last clinical assessment. Local control for SRS versus SRT was 94% versus 87% at 5 years and 90% versus 85% at 10 years (P=.2). Five- and 10-year actuarial rates of RT-induced trigeminal nerve dysfunction were 25% and 25% after SRS, compared with 7% and 12% after SRT (P=.01). Five- and 10-year actuarial rates of RT-induced facial nerve dysfunction were 15% and 15% after SRS, versus 13% and 15% after SRT (P=.93). In the 49 patients with serviceable hearing at baseline who were treated with SRT, hearing preservation was 55% at 3 years, 37% at 5 years, and 29% at 7 years. In multivariable analysis, better pretreatment ipsilateral pure tone average was significantly associated with hearing preservation (hazard ratio 1.03; 95% confidence interval 1.00-1.07; P=.04). CONCLUSIONS: Both SRS and SRT provided excellent long-term local control of vestibular schwannoma. Stereotactic radiosurgery was associated with higher rates of trigeminal nerve dysfunction. Even with a fractionated course, hearing preservation declined steadily with long-term audiometric follow-up.

Safety and tolerability of high-dose formoterol (via Aerolizer) and salbutamol in patients with chronic obstructive pulmonary disease.

To evaluate the safety and tolerability of high-dose formoterol and salbutamol in patients with chronic obstructive pulmonary disease (COPD). In this two-way crossover, double-blind, double-dummy study, 17 adults with mild-to-moderate COPD were randomized to receive either formoterol 24 microg (2 x 12 microg via Aerolizer), or salbutamol 600 microg (6 x 100 microg via metered-dose inhaler), and the appropriate double-dummy q.i.d. at 4-h intervals for 3 consecutive days (total daily dose: 96 and 2400 microg, respectively). After a 4-7-day washout period, patients were switched to the other treatment. Treatment with high-dose formoterol and salbutamol was equally well tolerated, with no reports of serious adverse events. Both agents were associated with decreased plasma potassium (mean minimum values: 3.4 and 3.3 mmol/l for formoterol and salbutamol, respectively; P=0.914), increased serum glucose (mean maximum values: 9.0 and 8.7 mmol/l, respectively; P=0.373), and small increases in mean QTc interval (mean maximum 439 ms with both treatments; P=0.813). No clinically relevant between-treatment differences in adverse events or laboratory values occurred. Both drugs improved lung function (mean maximum forced expiratory volume in 1s [FEV(1)] 2.6 l with both treatments; P=0.624), with the improvement being significantly greater with formoterol than with salbutamol on all 3 days of treatment (mean area under the curve [AUC](0-24 h) of FEV(1) formoterol vs. salbutamol on days 1-3, all P<0.05). High-dose formoterol via Aerolizer (up to 96 microg/day) has a comparable tolerability profile to that of salbutamol in patients with mild-to-moderate COPD.

The effect of glucose administration and the emotional content of words on heart rate and memory.

The effects of glucose administration and emotionality of target material on heart rate and memory were examined in a double-blind, placebo-controlled, balanced crossover study. Memory for neutral and emotional words was tested in 20 young adults following a glucose drink and a placebo. Heart rate and blood glucose were also measured. Emotional words were recalled and recognized better than neutral words in both drink conditions but there was no direct effect of drink type on memory. During the neutral word memory tasks, similar heart rate deceleration was observed in both drink conditions. However, during the processing of emotional material, heart rates were lowered in the placebo condition and relatively increased in the glucose condition. These results further differentiate the physiological responses involved during memory for affective and neutral material.

Perforating corneal ulceration in a patient with lung metastatic adenocarcinoma treated with gefitinib: a case report.

We present a case of a sixty-year-old female who presented with sudden onset of painless loss of vision in one eye due to a perforated corneal ulcer, following three months of treatment with gefitinib, a selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor for metastatic adenocarcinoma of the lung with confirmed EGFR gene mutation. The eye did not show any sign of infection or inflammation and had no associated lid problems to account for the development of corneal ulceration. The patient went on to have a corneal graft surgery but postoperatively developed corneal graft melt. This paper aims to raise awareness among ophthalmologists and oncologists of the probable association between gefitinib and corneal ulceration.

Safety and tolerability of high-dose formoterol (Aerolizer) and salbutamol (pMDI) in patients with mild/moderate, persistent asthma.

This double-blind, double-dummy, crossover study evaluated the tolerability of high-dose formoterol and salbutamol. Sixteen adults with mild/moderate persistent asthma (FEV1 > or = 70% predicted) were randomized to receive either formoterol 36 microg three times daily (TID) at 5-h intervals via Aerolizer (total daily dose 108 microg), or salbutamol 600 microg TID via pressurized metered-dose inhaler (total daily dose 1800 microg) for 3 consecutive days. After a 3-7-day washout period patients received the other treatment. FEV1 was measured 15 min pre-dose and 2 h post-dose. Both formoterol and salbutamol were associated with decreased plasma potassium (mean of minimum values: 3.4 and 3.6 mmol/L, respectively; P<0.001), increased serum glucose (mean of maximum values: 8.3 and 7.9 mmol/L, respectively; P=0.021), and small increases in mean QTc interval (mean of maximum values: 428.8 and 417.4 ms, respectively; P<0.001). However, none of these effects was clinically significant. Both treatments increased FEV1 to a mean maximum of 4.6 L (P=0.613), but the mean FEV1 AUC(0-72)h for formoterol was significantly greater than for salbutamol (302.2 L h, vs. 277.4 L h; P<0.001). No patients discontinued due to treatment-related adverse events. High-dose formoterol via Aerolizer did not produce any clinically significant systemic effects in patients with mild/moderate asthma.