Is the Management of Rectal Cancer Using a Watch and Wait Approach Feasible, Safe and Effective in a Publicly Funded General Hospital?

AIMS: Although there is emerging evidence to suggest equivalent oncological outcomes using a watch and wait approach compared with primary total mesorectal excision surgery, there is a paucity of evidence about the safety and efficacy of this approach in routine clinical practice. Here we report the long-term outcomes and quality of life from patients managed with watch and wait following a clinical complete response (cCR) to neoadjuvant therapy. MATERIALS AND METHODS: Patients with adenocarcinoma of the rectum with cCR following neoadjuvant therapy managed using watch and wait were retrospectively identified. Demographic data, performance status, pretreatment staging information, oncological and surgical outcomes were obtained from routinely collected clinical data. Quality of life was measured by trained clinicians during telephone interviews. RESULTS: Over a 7-year period, 506 patients were treated for rectal cancer, 276 had neoadjuvant therapy and 72 had a cCR (26.1%). Sixty-three were managed with watch and wait. Thirteen patients had mucosal regrowth. There was no significant difference in the incidence of metastatic disease between the surgical and watch and wait cohorts (P = 0.38). The 13 patients with mucosal regrowth underwent salvage surgery. Eleven of the patients who underwent surgical resection had R0 resections. There was also a statistically and clinically significant improvement in the Functional Assessment of Cancer Therapy - Colorectal (FACT-C) trial outcome index (P = 0.022). CONCLUSION: This study shows that watch and wait is safe and effective outside of tertiary referral centres. It suggests that an opportunistic cCR is durable and when mucosal regrowth occurs it can be salvaged. Finally, we have shown that quality of life is probably improved if a watch and wait approach is adopted.

Quantitative examination of isometric tongue protrusion forces in children with oro-facial dysfunctions or myofunctional disorders.

Oro-facial dysfunctions (OFD) or oro-facial myofunctional disorders in children lead to severe problems in teeth and jaw position, articulation, chewing and swallowing. The forces of the tongue, the central muscle for articulation, chewing and swallowing are focused on in several studies. In this examination, isometric tongue protrusion forces (TPF) of children with OFD and controls were compared. Thirty participants with OFD and 30 controls were presented a target force level as a straight line on a monitor that they were supposed to match by generating an isometric tongue force for different target levels (0.25 N and 0.5 N). Correlations of the severity of OFD (symptom score) with the capacities of the TPF 0.25 N and 0.5 N were calculated. Statistical differences were obvious in TPF variability and the accuracy, depending on the weight. Tongue contact time, expressed as per cent (TCT, total contact: 100%), was significantly lower in children with OFD (P = .005). Mean and median TPF was not different between groups. The predictive value of TPF for OFD revealed a level of 58.6% for TPF 0.25 N and 74.5% for TPF 0.5 N. Correlations of the severity of OFD were seen for some parameters. Subjects with OFD show significantly lower competencies in accuracy and endurance of tongue protrusion forces. This may have a high impact on phenotyping children with OFD and influence therapeutical approaches.

Two non-parametric methods for derivation of constraints from radiotherapy dose-histogram data.

Dose constraints based on histograms provide a convenient and widely-used method for informing and guiding radiotherapy treatment planning. Methods of derivation of such constraints are often poorly described. Two non-parametric methods for derivation of constraints are described and investigated in the context of determination of dose-specific cut-points-values of the free parameter (e.g., percentage volume of the irradiated organ) which best reflect resulting changes in complication incidence. A method based on receiver operating characteristic (ROC) analysis and one based on a maximally-selected standardized rank sum are described and compared using rectal toxicity data from a prostate radiotherapy trial. Multiple test corrections are applied using a free step-down resampling algorithm, which accounts for the large number of tests undertaken to search for optimal cut-points and the inherent correlation between dose-histogram points. Both methods provide consistent significant cut-point values, with the rank sum method displaying some sensitivity to the underlying data. The ROC method is simple to implement and can utilize a complication atlas, though an advantage of the rank sum method is the ability to incorporate all complication grades without the need for grade dichotomization.

SU-E-T-255: A Novel Rectal Obturator for Prostate Radiotherapy Improves the Spatial Distribution of Dose and Reduces the Predicted Risk for Rectal Bleeding and Subjective Sphincter Control.

PURPOSE: To investigate the effects of an endorectal device during prostate radiotherapy on the spatial distribution of dose to the ano-rectal region and quantify implications for normal-tissue-complication probabilities. METHODS: Twenty-three patients with localised prostate cancer, referred for external beam radiotherapy had 2 CT scans acquired, without and with the rectal obturator (ProSpare) in-situ. For each patient two dose distributions were generated, based on both CT scans. Dose-surface maps for the rectal surface and the anal surface were generated and mean dose as well as a spatial measure (circumference of the dose distribution) were determined for all patients, with and without ProSpare. Using previously published NTCP models, the effect of ProSpare on NTCP was investigated for rectal bleeding and subjective sphincter control. RESULTS: In a previous study subjective sphincter control correlated strongest with mean dose and lateral extent at 53 Gy. The use of ProSpare resulted in a highly significant reduction of the lateral extent at 53 Gy (p=0.006), mean dose (p=0.0009) and NTCP according to the LKB model (p=0.002 for grade 2 and p=0.001 for grade >=1). In a previous study we reported that rectal bleeding correlated most strongly with the lateral extent at 55 Gy and presented the constraint that it should not exceed 42% of the circumference. Using ProSpare resulted in a significant reduction of the lateral extent at 55 Gy (p=0.001) and significantly more patients met that proposed constraint (p=0.047). ProSpare resulted in a significant reduction of NTCP for grade-2 rectal bleeding (p=0.007) and a reduction for rectal bleeding grade >=1 (p=0.053). CONCLUSIONS: ProSpare resulted in a significant reduction of mean dose to the anal sphincter and a significant reduction of the lateral extent at 55 Gy. This corresponded to a significant reduction in the predicted risk of reporting subjective sphincter control and grade-2 rectal bleeding.

Using Bayesian logistic regression to evaluate a new type of dosimetric constraint for prostate radiotherapy treatment planning.

PURPOSE: Modern radiotherapy treatments can be optimized using dose-volume constraints which specify the volume of tumor and organs-at-risk receiving a given threshold dose. Careful derivation and evaluation of rectal constraints is essential to allow safe dose escalation in radiotherapy of prostate cancer. The authors present a new type of hybrid dosimetric constraint which comprises both volumetric and spatial factors of the dose-distribution. The authors also propose a framework to evaluate these constraints. METHODS: The authors used data from the RT01 prostate radiotherapy trial (ISRCTN 47772397) to derive this set of hybrid constraints for the rectum based on measures extracted from dose-surface maps. For comparison, the authors also derive a set of dose-volume constraints. In order to evaluate these dosimetric constraints, the authors propose a new framework for predicting radiation-induced toxicities using Bayesian logistic regression with high-order interactions. The predictive power of the new RT01-based constraints, as well as of two sets of rectal dose-volume constraints proposed in the recent literature-The constraints proposed by other researchers [C. Fiorino, G. Fellin, T. Rancati, V. Vavassori, C. Bianchi, V. C. Borca, G. Girelli, M. Mapelli, L. Menegotti, S. Nava, and R. Valdagni, "Clinical and dosimetric predictors of late rectal syndrome after 3D-CRT for localized prostate cancer: Preliminary results of a multicenter prospective study," Int. J. Radiat. Oncol., Biol., Phys. 70, 1130-1137 (2008)] and the constraints used in the conventional or hypofractionated high dose intensity modulated radiotherapy for prostate cancer (CHHiP) trial [C. P. South, V. S. Khoo, O. Naismith, A. Norman, and D. P. Dearnaley, "A comparison of treatment planning techniques used in two randomised UK external beam radiotherapy trials for localised prostate cancer," Clin. Oncol. (R Coll. Radiol) 20, 15-21 (2008)]--were evaluated using a tenfold cross-validation with follow-up data from the RT01 trial. The predictive power was quantified using receiver-operator characteristic (ROC) curves. Toxicities considered were rectal bleeding, loose stools, and a global toxicity score. RESULTS: Dose-volume constraints had less predictive power than the new type of hybrid constraints. A probabilistic model for predicting rectal bleeding based on the dose-volume constraints proposed by other researchers [C. Fiorino, G. Fellin, T. Rancati, V. Vavassori, C. Bianchi, V. C. Borca, G. Girelli, M. Mapelli, L. Menegotti, S. Nava, and R. Valdagni, "Clinical and dosimetric predictors of late rectal syndrome after 3D-CRT for localized prostate cancer: Preliminary results of a multicenter prospective study," Int. J. Radiat. Oncol., Biol., Phys. 70, 1130-1137 (2008)], the CHHiP dose-volume constraints, the RT01-based dose-volume constraints, and the hybrid constraints resulted in average areas under the ROC curves of 0.56, 0.58, 0.62, and 0.67, respectively. For predicting loose stools, the corresponding values were 0.57, 0.53, 0.66, and 0.71, respectively. The areas under the respective ROC curves for predicting the global toxicity score were 0.58, 0.55, 0.61, and 0.63. CONCLUSIONS: Thus, imposing the new type of hybrid constraints when generating a treatment plan should result in a reduction in the incidence of radiation-induced late rectal toxicity.