Feasibility of a multiparametric MRI protocol for imaging biomarkers associated with neoadjuvant radiotherapy for soft tissue sarcoma.

Objective: Soft tissue sarcoma (STS) is a rare malignancy with a 5 year overall survival rate of 55%. Neoadjuvant radiotherapy is commonly used in preparation for surgery, but methods to assess early response are lacking despite pathological response at surgery being predictive of overall survival, local recurrence and distant metastasis. Multiparametric MR imaging (mpMRI) is used to assess response in a variety of tumours but lacks a robust, standardised method. The overall aim of this study was to develop a feasible imaging protocol to identify imaging biomarkers for further investigation. Methods: 15 patients with biopsy-confirmed STS suitable for pre-operative radiotherapy and radical surgery were imaged throughout treatment. The mpMRI protocol included anatomical, diffusion-weighted and dynamic contrast-enhanced imaging, giving estimates of apparent diffusion coefficient (ADC) and the area under the enhancement curve at 60 s (iAUC60). Histological analysis of resected tumours included detection of CD31, Ki67, hypoxia inducible factor and calculation of a hypoxia score. Results: There was a significant reduction in T1 at visit 2 and in ADC at visit 3. Significant associations were found between hypoxia and pre-treatment iAUC60, pre-treatment ADC and mid-treatment iAUC60. There was also statistically significant association between mid-treatment ADC and Ki67. Conclusion: This work showed that mpMRI throughout treatment is feasible in patients with STS having neoadjuvant radiotherapy. The relationships between imaging parameters, tissue biomarkers and clinical outcomes warrant further investigation. Advances in knowledge: mpMRI-based biomarkers have good correlation with STS tumour biology and are potentially of use for evaluation of radiotherapy response.

Palliative Radiation Therapy in Bladder Cancer-Importance of Patient Selection: A Retrospective Multicenter Study.

PURPOSE: To investigate the effectiveness of palliative pelvic radiation therapy (PRT) in patients with bladder cancer and identify factors associated with treatment outcome. METHODS AND MATERIALS: Patients with bladder cancer receiving PRT were identified retrospectively from 2 cancer centers between 2014 and 2017. Patients were stratified by age, stage, performance status, comorbidities, previous chemotherapy, previous radiation therapy, and radiation therapy protocol. Patients were followed up at 6 weeks after radiation therapy (RT). Median overall survival (mOS) from the last fraction of RT was calculated. Death within 30 days of RT or noncompletion of treatment were considered as futile treatment. RESULTS: Two hundred forty-one patients were identified as receiving PRT. A variety of RT protocols were used: 8 Gy in 1 fraction (11%), 21 Gy in 3 fractions (15%), 20 Gy in 5 fractions (18%), 36 Gy in 6 fractions (36%), and 27.5 to 30 Gy in 8 to 10 fractions (18%). Thirty-eight percent of patients were of poor performance status (Eastern Cooperative Oncology Group performance status ≥3), and 46.5% had significant comorbidities (Adult Comorbidity Evaluation-27 ≥2). The mOS from the last fraction of RT was 153 days (0-1289 days). The 30-day mortality after radiation therapy was 18% (n = 44), and the rate of incomplete planned radiation therapy treatment was 14% (n = 33). First follow-up information was available in 62% (n = 150) of patients. Median time to this follow-up was 49 days (14-238 days). At first follow-up at about 6 weeks after the last fraction of radiation therapy, symptoms were reported in 150 of 200 (75%) living patients; 80 of 150 (53%) patients reported improvement in symptoms after treatment. There were significant differences in mOS with stage, performance status, and comorbidities. CONCLUSIONS: One in 4 patients either did not complete the planned RT course or died within 30 days of treatment. These patients were unlikely to have received maximal benefit from treatment but may have experienced side effects, making treatment futile. Patients with good performance status and earlier stage disease survived longer. Patient selection and comprehensive assessment are crucial in selecting appropriate patients for treatment.

Patient Perceptions of the Impact of Treatment (Surgery and Radiotherapy) for Soft Tissue Sarcoma.

BACKGROUND AND OBJECTIVES: Treatment for soft tissue sarcoma (STS) is challenging for patients. This study aimed to gain an in-depth understanding of patients' experiences of STS treatment, including whether the sequence of treatment (preoperative or postoperative radiotherapy) influences patient perceptions. METHODS: Face-to-face semi-structured interviews were conducted with nineteen patients who had been treated for STS with surgery and radiotherapy between 2011 and 2016. Topics discussed included perceptions of treatment, social support, and coping mechanisms. Qualitative, inductive, thematic analysis was conducted and structured using the Framework approach. RESULTS: Treatment sequence itself did not appear to cause concern, but uncertainty regarding treatment and side effects could negatively impact participants. Social relationships and individual coping strategies influenced participants' experiences of treatment. CONCLUSIONS: Participants' perceptions of the treatment process varied; the experience was highly individual. It is important to ensure individual psychosocial and information needs are met. In particular, the removal of uncertainty regarding treatment is important in supporting patients undergoing treatment for soft tissue sarcoma.

Does magnetic resonance imaging improve soft tissue sarcoma contouring for radiotherapy?

OBJECTIVE: Soft tissue sarcomas (STS) are a rare, heterogeneous tumour group. Radiotherapy improves local control. CT is used to plan radiotherapy, but has poor soft tissue definition. MRI has superior soft tissue definition. Contour variation amongst oncologists is an important factor in treatment failure. This study is the first to directly compare STS tumour contouring using CT vs MRI. METHODS: Planning CT and T 2 weighted MR images of eight patients with STS were distributed to four oncologists. Gross tumour volume was contoured on both imaging modalities using in-house software. Images were recontoured 6 weeks later. The mean distance to agreement (DTA), standard deviation of the DTA, dice similarity coefficient (DSC) and contour volume were calculated for each oncologist and compared to a median contour volume. Results for CT and MRI were compared using a pairwise Student's t-test. RESULTS: When comparing MRI to CT, tumour volumes were significantly smaller, with a difference of 21.4 cm3 across all patients (p = 0.008). There was not a statistically significant difference in the mean distance to agreement or dice similarity coefficient, but the standard deviation of the DTA showed a statistically significant improvement ( p = 0.04). For intraobserver variation, there was no statistically significant improvement using MRI vs CT. CONCLUSION: Oncologists contour smaller tumour volumes using MRI, with reduced interobserver variation. Improving the reliability and consistency of contouring is needed for improved quality assurance. ADVANCES IN KNOWLEDGE: With further experience, the use of MRI in STS radiotherapy planning may reduce variation between oncologists and contribute to improved local control and reduced treatment toxicities.

Physical after-effects in men undergoing prostate biopsy in routine clinical practice: Results from the PiCTure study.

BACKGROUND: As the incidence of prostate cancer has, until recently, increased in most developed countries, the rates of prostate biopsies, required for histological diagnosis, will also have increased. Little is known about the physical after-effects of prostate biopsy outside randomised control trials. We investigate reports on the physical effect of prostate biopsy undertaken in men in routine practice. METHODS: A self-completed questionnaire was given to men living in the Republic of Ireland (RoI) or Northern Ireland 4 to 6 weeks after prostate biopsy. Men were asked about whether they experienced specific physical after-effects postbiopsy (raised temperature/pain/bleeding/erectile dysfunction/urinary retention) and, if so, their severity and duration, and any associated health care uses. Binomial and ordinal logistic regression was used to investigate factors associated with postbiopsy after-effects (presence/absence) and number of after-effects reported, respectively. RESULTS: Postbiopsy after-effects were common with 88.1% of 335 respondents reporting at least 1 after-effect; 21% reported at least 3. The odds of increasing number of after-effects was over 2-fold in men with both intermediate (odds ratio [OR] = 2.59, 95% CI: 1.52-4.42) and high (OR = 2.52, 95% CI: 1.28-4.94) levels of health anxiety and for men who had had multiple previous biopsies (adjusted OR = 2.02, 95% CI: 1.20-3.41). A total of 21.3% of men who experienced after-effects reported that they were worse than expected, 11.5% with after-effects reported contacting their doctor or local pharmacy, 14.6% contacted hospital services, and 3.1% of men with after-effects were admitted to hospital with an average stay of 5.4 nights (standard deviation = 6.3). CONCLUSION: Physical after-effects following prostate biopsy in routine practice are common, and in some men, serious enough to warrant contacting hospital or community services. Men with increased health anxiety or who undergo multiple biopsies might benefit from additional support.

Do men regret prostate biopsy: Results from the PiCTure study.

BACKGROUND: Understanding men's experience of prostate biopsy is important as the procedure is common, invasive and carries potential risks. The psychological aspects of prostate biopsy have been somewhat neglected. The aim of this study was to explore the level of regret experienced by men after prostate biopsy and identify any associated factors. METHODS: Men attending four clinics in Republic of Ireland and two in Northern Ireland were given a questionnaire to explore their experience of prostate biopsy. Regret was measured on a Likert scale asking men how much they agreed with the statement "It [the biopsy] is something I regret." RESULTS: Three hundred thirty-five men responded to the survey. The mean age was 63 years (SD ±7 years). Three quarters of respondents (76%) were married or co-habiting, and (75%) finished education at primary or secondary school level. For just over two thirds of men (70%) their recent biopsy represented their first ever prostate biopsy. Approximately one third of men reported a diagnosis of cancer, one third a negative biopsy result, and the remaining third did not know their result. Two thirds of men reported intermediate or high health anxiety. 5.1% of men agreed or strongly agreed that they regretted the biopsy. CONCLUSIONS: Level of regret was low overall. Health anxiety was the only significant predictor of regret, with men with higher anxiety reporting higher levels of regret than men with low anxiety (OR = 3.04, 95% CI 1.58, 5.84). Men with high health anxiety may especially benefit from careful counselling before and after prostate biopsy.

Outcomes following chemoradiotherapy for N3 head and neck squamous cell carcinoma without a planned neck dissection.

OBJECTIVES: The optimal management of the N3 neck in head and neck squamous cell carcinoma (HNSCC) remains controversial. We report the outcomes of patients with N3 disease treated with a strategy of concurrent chemo-radiotherapy (CRT)±induction chemotherapy (ICT) without a planned neck dissection. MATERIALS AND METHODS: Forty patients with HNSCC N3 disease treated between January 2004 and December 2010 were retrospectively identified. Inclusion criteria for the study were: non-nasopharyngeal HNSCC, N3 nodal disease, intention to treat with CRT±ICT. RESULTS: Median age was 60 (range 39-74). Median follow up was 32 months (range 8-88). 34 (85%) of patients received ICT. 35 patients received cisplatin-CRT, 4 carboplatin-CRT and 1 patient was treated with radiotherapy alone due to ICT toxicity. 27 (67.5%) patients had a complete response (CR) to CRT. 5 (12.5%) patients had an incomplete response in both the primary and nodal sites. 8 (20%) patients had a CR in the primary site but incomplete in the nodal regions. The crude rate of regional failure following a CR was 3/27 (11.2%). Isolated regional failure occurred in 1/27 (3.7%) patients who had achieved a CR post-CRT. 3 year overall survival, disease free survival, locoregional control, local control and regional control in the whole cohort were 51.4%, 49.6%, 65.7%, 77.3%, 69.3%, and in patients with a CR were 73.3%, 70.0%, 86.6%, 90.5% and 91.7% respectively. CONCLUSION: Isolated regional nodal failure is rare following a complete response to CRT for N3 HNSCC managed without a planned neck dissection.

The Impact of (18)F-FDG PET CT Prior to Chemoradiotherapy for Stage III/IV Head and Neck Squamous Cell Carcinoma.

Introduction. To determine the value of a FDG-PET-CT scan in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) prior to chemoradiotherapy. Materials and Methods. Consecutive patients with stage III or IV HNSCC who had undergone a staging FDG-PET-CT scan prior to chemoradiotherapy between August 2008 and April 2011 were included. Clinical details and conventional imaging (CT and/or MRI) were, retrospectively, reviewed, a TNM stage was assigned, and levels of cervical lymph node involvement were documented. This process was repeated with the addition of FDG-PET-CT. Radiotherapy plans were reviewed for patients with an alteration identified on TNM staging and/or nodal level identification with FDG-PET-CT and potential alterations in radiotherapy planning were documented. Results. 55 patients were included in the analysis. FDG-PET-CT altered the TNM stage in 17/55 (31%) of patients, upstaging disease in 11 (20%) and downstaging in 6 (11%); distant metastases were identified by FDG-PET-CT in 1 (2%) patient. FDG-PET-CT altered the lymph node levels identified in 22 patients (40%), upclassifying disease in 16 (29%) and downclassifying in 6 (11%). Radiotherapy plans were judged retrospectively to have been altered by FDG-PET-CT in 10 patients (18%). Conclusions. The use of FDG-PET-CT potentially impacts upon both treatment decisions and radiotherapy planning.

Enteral feeding outcomes after chemoradiotherapy for oropharynx cancer: a role for a prophylactic gastrostomy?

To determine the outcomes of patients managed with different routes of enteral feeding during chemoradiotherapy for oropharynx cancer. The hospital and dietetic records of consecutive patients with oropharynx squamous cell carcinoma treated between January 2007 and June 2009 with concurrent chemoradiotherapy were reviewed retrospectively. One hundred and four patients were analysed. Seventy-one received a prophylactic gastrostomy, 21 were managed with a strategy of NG tube as required and 12 received a therapeutic gastrostomy. Patients with a prophylactic gastrostomy commenced enteral feeding a median of 24 days after commencing radiotherapy, compared with a median of 41 days (p<0.001) for the NG as required group. Comparing prophylactic gastrostomy, NG as required and therapeutic gastrostomy, median number of unplanned inpatient days were 6, 14 and 7, respectively (p<0.01 for prophylactic gastrostomy vs. NG as required). Mean percentage weight loss at the end of treatment (6.1% vs. 7.1% vs. 5.2%, respectively) and at 6 months post-radiotherapy (11.7%, 14.3% and 8.9%) were similar in all groups (p=0.23). There was no significant difference in type of diet post-radiotherapy between prophylactic gastrostomy and NG as required groups (p=0.22). Median duration of enteral feeding was 181, 64 and 644 days, respectively (p<0.01 for prophylactic gastrostomy vs. NG as required). Use of a prophylactic gastrostomy (p<0.01) and higher T stage (p<0.01) were associated with increased duration of enteral feeding on a multivariate analysis. These data reinforce concerns regarding the detrimental impact of prophylactic gastrostomy placement upon long-term enteral feed dependence.

Feasibility and efficacy of induction docetaxel, cisplatin, and 5-fluorouracil chemotherapy combined with cisplatin concurrent chemoradiotherapy for nonmetastatic Stage IV head-and-neck squamous cell carcinomas.

PURPOSE: To report the experience of treating selected fit patients with locally advanced head-and-neck squamous cell carcinoma with three cycles of induction TPF (docetaxel 75 mg/m(2), cisplatin 75 mg/m(2), 5-fluorouracil 750 mg/m(2), Days 2-5) followed by concurrent three-weekly bolus cisplatin 100 mg/m(2) chemoradiotherapy. METHODS AND MATERIALS: Between March 2006 and February 2010, 66 patients with nonmetastatic Stage IV head-and-neck squamous cell carcinoma were treated in a single institution with three cycles of induction TPF, followed by radical radiotherapy with concurrent cisplatin 100 mg/m(2). RESULTS: Median age was 54 years (range, 33-69 years). Median follow-up was 21 months (range, 4-55 months). During TPF, Grade 3 toxicity occurred in 18 patients (27%), dose modifications in 10 (15%), delays in 3 (5%), and unplanned admissions in 6 (9%); a clinical tumor response was documented in 60 patients (91%). Median time from the final cycle of TPF to commencing radiotherapy was 22 days. Sixty-two patients (94%) received radical radiotherapy, and all completed treatment with no delays ≥3 days. One, two, and three cycles of concurrent cisplatin were delivered to 18 patients (29%), 38 patients (61%), and 3 patients (5%), respectively. Ninety-two percent of patients received enteral feeding; median weight loss during treatment was 7%. Forty-two patients (68%) had unplanned admissions with no on-treatment deaths. Three unrelated deaths occurred after treatment. At 1 year after treatment, 21% of patients without disease progression remained gastrostomy dependent. Of 58 assessable patients, 50 (86%) achieved a complete response after treatment. One- and 2-year progression-free survival, cause-specific survival, and overall survival were 88%, 92%, and 86% and 80%, 85%, and 80%, respectively. CONCLUSION: The combination of induction TPF with concurrent cisplatin chemoradiotherapy in patients with locally advanced head and neck squamous cell carcinoma is tolerable, with encouraging efficacy.

Recurrence patterns of locally advanced head and neck squamous cell carcinoma after 3D conformal (chemo)-radiotherapy.

BACKGROUND: To establish recurrence patterns among locally advanced head and neck non-nasopharyngeal squamous cell carcinoma (HNSCC) patients treated with radical (chemo-) radiotherapy and to correlate the sites of loco-regional recurrence with radiotherapy doses and target volumes METHOD: 151 locally advanced HNSCC patients were treated between 2004-2005 using radical three-dimensional conformal radiotherapy. Patients with prior surgery to the primary tumour site were excluded. The sites of locoregional relapses were correlated with radiotherapy plans by the radiologist and a planning dosimetrist. RESULTS: Median age was 59 years (range:34-89). 35 patients had stage III disease, 116 patients had stage IV A/B. 36 patients were treated with radiotherapy alone, 42 with induction chemotherapy, 63 with induction and concomitant chemoradiotherapy and 10 concomitant chemoradiotherapy. Median follow-up was 38 months (range 3-62). 3-year cause specific survival was 66.8%. 125 of 151 (82.8%) achieved a complete response to treatment. Amongst these 125 there were 20 local-regional recurrence, comprising 8 local, 5 regional and 7 simultaneous local and regional; synchronous distant metastases occurred in 7 of the 20. 9 patients developed distant metastases in the absence of locoregional failure. For the 14 local recurrences with planning data available, 12 were in-field, 1 was marginal, and 1 was out-of-field. Of the 11 regional failures with planning data available, 7 were in-field, 1 was marginal and 3 were out-of-field recurrences. CONCLUSION: The majority of failures following non-surgical treatment for locally advanced HNSCC were loco-regional, within the radiotherapy target volume. Improving locoregional control remains a high priority.

A single centre experience with sequential and concomitant chemoradiotherapy in locally advanced stage IV tonsillar cancer.

BACKGROUND: Chemo-radiotherapy offers an alternative to primary surgery and adjuvant therapy for the management of locally advanced stage IV squamous cell carcinomas of the tonsil. METHODS: A retrospective analysis was performed of the outcomes of 41 patients with locoregionally advanced squamous cell carcinoma of the tonsil treated non-surgically at the Yorkshire Cancer Centre between January 2004 and December 2005. Due to long radiotherapy waiting times, patients received induction chemotherapy with cisplatin and 5-fluorouracil followed by either cisplatin concurrent chemoradiotherapy or radiotherapy alone. RESULTS: Median age was 55 years (range 34-76 years) and 28 (68%) patients were male. 35/41 patients (85%) received 2 or more cycles of induction chemotherapy. Following induction chemotherapy, 32/41 patients (78%) had a clinical response. Concomitant chemotherapy was given to 30/41 (73%). All patients received the planned radiotherapy dose with no delays. There were no treatment related deaths. Six (15%) patients had gastrostomy tubes placed before treatment, and 22 (54%) required nasogastric tube placement during or after treatment for nutritional support. 17 patients required unplanned admissions during treatment for supportive care. At 4 months post treatment assessment 35 out of 41 (85%) patients achieved complete clinical and radiographic response. Median follow-up is 38 months (8-61 months). Local and regional control rate in complete responders at 3 years was 91%. Distant metastases have been found in 4 (9.8%) patients. Three year progression-free survival rate in all patients is 75%. The 3-year cause specific survival and overall survival are 75% and 66% respectively. CONCLUSION: Cisplatin-based induction and concurrent chemoradiotherapy provides excellent tumour control with acceptable toxicity for patients with locally advanced tonsillar cancer.

Healthcare utilization among women with physical disabilities.

BACKGROUND: Current published data indicate barriers and deficiencies in healthcare for women with physical disabilities. Yet, information regarding the influence of secondary conditions and demographic variables on the actual utilization of general health and rehabilitative services is limited. This research examined this issue. DESIGN: Survey research SETTING: Metropolitan Philadelphia region PARTICIPANTS: 170 women between 21 and 65 years of age with physical disabilities RESULTS: Most (96%) women had seen a general healthcare provider (eg, personal physician or gynecologist) in the past 6 months, with 60% reporting seeing such a provider 3 or more times. Despite this high frequency, many women had not had routine preventive gynecologic cancer screening services in the past 5 years. Additionally, respondents reported experiencing on average 12 secondary complications in the past year that moderately impaired their functioning. Many of these complications (fatigue, spasticity, deconditioning, joint pain, depression, social isolation) are preventable. Despite these complications, only about half of the women had seen a rehabilitative service provider (eg, physical therapist, mental health worker) in the past 6 months. Women who saw their general healthcare provider most frequently were more likely to also be receiving services from a rehabilitative service provider. CONCLUSION: General healthcare providers are frequently seeing women with physical disabilities. Healthcare providers have the ability and opportunity to enhance the health and wellness of this population. Particular attention should be focused on providing preventive healthcare services, including gynecologic cancer screenings and prevention and management of secondary conditions that accompany disability.