Patient-reported outcomes in PROSPECT trial (Alliance N1048) – FOLFOX is not a panacea

The PROSPECT was a randomized phase III trial that included patients with resectable rectal cancer (clinical stage cT2-3N+ or cT3N0). The trial aimed to test the hypothesis that pre-operative chemotherapy consisting of 6 cycles of FOLFOX given over a 12-week period, followed by total mesorectal excision (TME) surgery, was non-inferior to pre-operative long-course chemoradiotherapy (CRT). The primary endpoint of the study was disease-free survival (DFS), and patients were also monitored for other relevant oncological outcomes such and health-related quality of life (HRQoL) using patient-reported outcome (PRO) tools [1, 2]

Identifying social distress: a cross-sectional survey of social outcomes 12 to 36 months after colorectal cancer diagnosis

Purpose: To establish the prevalence and determinants of poor social outcomes after a diagnosis of colorectal cancer (CRC). Patients and Methods: All 12- to 36-month survivors of CRC (International Classification of Diseases [10th revision] codes C18 to C20) diagnosed in 2010 or 2011 and treated in the English National Health Service were identified and sent a questionnaire from their treating cancer hospital. This included the Social Difficulties Inventory, a 16-item scale of social distress (SD) comprising everyday living, money matters, and self and others subscales, plus five single items. Sociodemographic and clinical data were also collected. Analyses using descriptive statistics, 2 tests, and logistic regression models were conducted. Results: Response rate was 63.3% (21,802 of 34,467). Of the 21,802 participants, 17,830 (81.8%) completed all SD items; 2,688 (15.1%) of these 17,830 respondents were classified as experiencing SD (everyday living, 19.5%; money matters, 15.6%; self and others, 18.1%). Multivariable analysis demonstrated having three long-term conditions was the strongest predictor of SD (odds ratio [OR], 6.64; 95% CI, 5.67 to 7.77 compared with no long-term conditions), followed by unemployment (OR, 5.11; 95% CI, 4.21 to 6.20 compared with being employed), having recurrent or nontreatable disease (OR, 2.75; 95% CI, 2.49 to 3.04 compared with being in remission), and having a stoma (OR, 2.10; 95% CI, 1.86 to 2.36 compared with no stoma). Additional predictors of SD were young age (< 55 years), living in a more deprived area, nonwhite ethnicity, having advanced-stage disease, having undergone radiotherapy, and being a carer. Conclusion: Although it is reassuring a majority do not experience social difficulties, a minority reported significant SD 12 to 36 months after diagnosis of CRC. The identified clinical and social risk factors are easy to establish and should be used to target support

Prostate Stereotactic Ablative Radiation Therapy Using Volumetric Modulated Arc Therapy to Dominant Intraprostatic Lesions

PurposeTo investigate boosting dominant intraprostatic lesions (DILs) in the context of stereotactic ablative radiation therapy (SABR) and to examine the impact on tumor control probability (TCP) and normal tissue complication probability (NTCP).Methods and MaterialsTen prostate datasets were selected. DILs were defined using T2-weighted, dynamic contrast-enhanced and diffusion-weighted magnetic resonance imaging. Four plans were produced for each dataset: (1) no boost to DILs; (2) boost to DILs, no seminal vesicles in prescription; (3) boost to DILs, proximal seminal vesicles (proxSV) prescribed intermediate dose; and (4) boost to DILs, proxSV prescribed higher dose. The prostate planning target volume (PTV) prescription was 42.7 Gy in 7 fractions. DILs were initially prescribed 115% of the PTVProstate prescription, and PTVDIL prescriptions were increased in 5% increments until organ-at-risk constraints were reached. TCP and NTCP calculations used the LQ-Poisson Marsden, and Lyman-Kutcher-Burman models respectively.ResultsWhen treating the prostate alone, the median PTVDIL prescription was 125% (range: 110%-140%) of the PTVProstate prescription. Median PTVDIL D50% was 55.1 Gy (range: 49.6-62.6 Gy). The same PTVDIL prescriptions and similar PTVDIL median doses were possible when including the proxSV within the prescription. TCP depended on prostate α/β ratio and was highest with an α/β ratio = 1.5 Gy, where the additional TCP benefit of DIL boosting was least. Rectal NTCP increased with DIL boosting and was considered unacceptably high in 5 cases, which, when replanned with an emphasis on reducing maximum dose to 0.5 cm3 of rectum (Dmax0.5cc), as well as meeting existing constraints, resulted in considerable rectal NTCP reductions.ConclusionsBoosting DILs in the context of SABR is technically feasible but should be approached with caution. If this therapy is adopted, strict rectal constraints are required including Dmax0.5cc. If the α/β ratio of prostate cancer is 1.5 Gy or less, then high TCP and low NTCP can be achieved by prescribing SABR to the whole prostate, without the need for DIL boosting

Developing a class solution for Prostate Stereotactic Ablative Body Radiotherapy (SABR) using Volumetric Modulated Arc Therapy (VMAT)

Background and purpose To develop a class solution for prostate Stereotactic Ablative Radiotherapy (SABR) using Volumetric Modulated Arc Therapy (VMAT). Materials and methods Seven datasets were used to compare plans using one 360° arc (1FA), one 210° arc (1PA), two full arcs and two partial arcs. Subsequently using 1PA, fifteen datasets were compared using (i) 6 mm CTV–PTV margins, (ii) 8 mm CTV–PTV margins and (iii) including the proximal SV within the CTV. Monaco™ 3.2 (Elekta™) was used for planning with the Agility™ MLC system (Elekta™). Results Highly conformal plans were produced using all four arc arrangements. Compared to 1FA, 1PA resulted in significantly reduced rectal doses, and monitor units and estimated delivery times were reduced in six of seven cases. Using 6 mm CTV–PTV margins, planning constraints were met for all fifteen datasets. Using 8 mm margins required relaxation of the uppermost bladder constraint in three cases to achieve adequate coverage, and, compared to 6 mm margins, rectal and bladder doses significantly increased. Including the proximal SV required relaxation of the uppermost bladder and rectal constraints in two cases, and rectal and bladder doses significantly increased. Conclusions Prostate SABR VMAT is optimal using 1PA. 6 mm CTV–PTV margins, compatible with daily fiducial-based IGRT, are consistently feasible in terms of target objectives and OAR constraints

Health-related quality of life after colorectal cancer in England: a patient-reported outcomes study of individuals 12 to 36 months after diagnosis

Purpose: This population-level study was conducted to define the health-related quality of life (HRQL) of individuals living with and beyond colorectal cancer (CRC) and to identify factors associated with poor health outcomes. Patients and Methods: All individuals diagnosed with CRC in England in 2010 and 2011 who were alive 12 to 36 months after diagnosis were sent a questionnaire. This included questions related to treatment, disease status, other long-term conditions (LTCs), generic HRQL (EuroQol-5D), and cancer-specific outcomes (Functional Assessment of Cancer Therapy and Social Difficulties Inventory items). Results: The response rate was 63.3% (21,802 of 34,467 patients). One or more generic health problems were reported by 65% of respondents, with 10% of patients reporting problems in all five domains. The reporting of problems was higher than in the general population and was most marked in those age less than 55 years. Certain subgroups reported a higher number of problems, notably those with one or more other LTCs, those with active or recurrent disease, those with a stoma, and those at the extremes of the age range ( 85 years). Of respondents without a stoma, 16.3% reported no bowel control. Reversal of a stoma resulted in fewer severe bowel problems but more moderate problems than those who had never had a stoma. A quarter of rectal cancer respondents (25.1%) reported difficulties with sexual matters (compared with 11.2% of colon cancer respondents). Conclusion: This study demonstrates the success of a national patient-reported outcomes survey. The results have the potential to support system-wide improvement in health outcomes through the identification of particular challenges faced by individuals after treatment for CRC

Image-based consensus molecular subtyping in rectal cancer biopsies and response to neoadjuvant chemoradiotherapy

The development of deep learning (DL) models to predict the consensus molecular subtypes (CMS) from histopathology images (imCMS) is a promising and cost-effective strategy to support patient stratification. Here, we investigate whether imCMS calls generated from whole slide histopathology images (WSIs) of rectal cancer (RC) pre-treatment biopsies are associated with pathological complete response (pCR) to neoadjuvant long course chemoradiotherapy (LCRT) with single agent fluoropyrimidine. DL models were trained to classify WSIs of colorectal cancers stained with hematoxylin and eosin into one of the four CMS classes using a multi-centric dataset of resection and biopsy specimens (n = 1057 WSIs) with paired transcriptional data. Classifiers were tested on a held out RC biopsy cohort (ARISTOTLE) and correlated with pCR to LCRT in an independent dataset merging two RC cohorts (ARISTOTLE, n = 114 and SALZBURG, n = 55 patients). DL models predicted CMS with high classification performance in multiple comparative analyses. In the independent cohorts (ARISTOTLE, SALZBURG), cases with WSIs classified as imCMS1 had a significantly higher likelihood of achieving pCR (OR = 2.69, 95% CI 1.01–7.17, p = 0.048). Conversely, imCMS4 was associated with lack of pCR (OR = 0.25, 95% CI 0.07–0.88, p = 0.031). Classification maps demonstrated pathologist-interpretable associations with high stromal content in imCMS4 cases, associated with poor outcome. No significant association was found in imCMS2 or imCMS3. imCMS classification of pre-treatment biopsies is a fast and inexpensive solution to identify patient groups that could benefit from neoadjuvant LCRT. The significant associations between imCMS1/imCMS4 with pCR suggest the existence of predictive morphological features that could enhance standard pathological assessment