Dose Escalation Using Contact X-ray Brachytherapy After External Beam Radiotherapy as Nonsurgical Treatment Option for Rectal Cancer: Outcomes From a Single-Center Experience.

PURPOSE: To review the outcomes of rectal cancer patients treated with a nonsurgical approach using contact x-ray brachytherapy (CXB) when suspicious residual disease (≤3 cm) was present after external beam chemoradiation therapy/radiation therapy (EBCRT/EBRT). METHODS AND MATERIALS: Outcome data for rectal cancer patients referred to our institution from 2003 to 2012 were retrieved from an institutional database. These patients were referred after initial local multidisciplinary team discussion because they were not suitable for, or had refused, surgery. All selected patients received a CXB boost after EBCRT/EBRT. Most patients received a total of 90 Gy of CXB delivered in 3 fractions over 4 weeks. RESULTS: The median follow-up period was 2.5 years (range 1.2-8.3). Of 345 consecutive patients with rectal cancer referred to us, 83 with suspicious residual disease (≤3 cm) after EBCRT/EBRT were identified for a CXB boost. Their median age was 72 years (range 36-87), and 58 (69.9%) were men. The initial tumor stages were cT2 (n = 28) and cT3 (n = 55), and 54.2% were node positive. A clinical complete response (cCR) was achieved in 53 patients (63.8%) after the CXB boost that followed EBCRT/EBRT. Of these 53 patients, 7 (13.2%) developed a relapse after achieving a cCR, and the 6 patients (11.6%) with nonmetastatic regrowth underwent salvage surgery (100%). At the end of the study period, 69 of 83 patients (83.1%) were cancer free. CONCLUSIONS: Our data suggest that a CXB boost for selected patients with suspicious residual disease (≤3 cm) after EBCRT/EBRT can be offered as an alternative to radical surgery. In our series, patients with a sustained cCR had a low rate of local regrowth, and those with nonmetastatic regrowth could be salvaged successfully. This approach could provide an alternative treatment option for elderly or comorbid patients who are not suitable for surgery and those with rectal cancer who wish to avoid surgery.

Dose escalation using contact X-ray brachytherapy (Papillon) for rectal cancer: does it improve the chance of organ preservation?

OBJECTIVE: A watch and wait policy for patients with a clinical complete response (cCR) after external beam chemoradiotherapy (EBCRT) for rectal cancer is an attractive option. However, approximately one-third of tumours will regrow, which requires surgical salvage for cure. We assessed whether contact X-ray brachytherapy (CXB) can improve organ preservation by avoiding surgery for local regrowth. METHODS: From our institutional database, we identified 200 of 573 patients treated by CXB from 2003 to 2012. Median age was 74 years (range 32-94), and 134 (67%) patients were males. Histology was confirmed in all patients and was staged using CT scan, MRI or endorectal ultrasound. All patients received combined CXB and EBCRT, except 17 (8.5%) who had CXB alone. RESULTS: Initial cCR was achieved in 144/200 (72%) patients. 38/56 (68%) patients who had residual tumour received immediate salvage surgery. 16/144 (11%) patients developed local relapse after cCR, and 124/144 (86%) maintained cCR. At median follow up of 2.7 years, 161 (80.5%) patients were free of cancer. The main late toxicity was bleeding (28%). Organ preservation was achieved in 124/200 (62%) patients. CONCLUSION: Our data suggest that CXB can reduce local regrowth to 11% compared with around 30% after EBCRT alone. Organ preservation of 62% achieved was higher than reported in most published watch and wait studies. Advances in knowledge: CXB is a promising treatment option to avoid salvage surgery for local regrowth, which can improve the chance of organ preservation in patients who are not suitable for or refuse surgery.

Local Excision Techniques for Rectal Cancer After Neoadjuvant Chemoradiotherapy: What Are We Doing?

BACKGROUND: Recent evidence shows that the majority of rectal cancers demonstrate occult tumor scatter after neoadjuvant chemoradiotherapy that can extend for several centimeters under adjacent normal-appearing mucosa beside the residual mucosal abnormality or scar. OBJECTIVE: This systematic review aimed to determine all of the published selection criteria and technical descriptions for local excision to date with regard to this phenomenon. DATA SOURCES: PubMed, MEDLINE, and Embase were searched using the following key words: rectal cancer, local excision, radiotherapy, and neoadjuvant. STUDY SELECTION: Studies that assessed local excision of rectal cancer after neoadjuvant chemoradiotherapy were included. Duplicate series were excluded from final analysis. INTERVENTION: All of the data points were tabulated and analyzed using Microsoft Excel. MAIN OUTCOME MEASURES: Criteria for patient selection, surgical technique, clinical restaging, pathologic assessment, and indications for completion surgery were analyzed. RESULTS: After exclusions, data from 25 studies that in total evaluated local excision in 1001 patients were included. Compared with the single accepted technique of total mesorectal excision, described techniques for local excision after neoadjuvant therapy demonstrate significant variability in many critical technical issues, such as marking/tattooing original tumor margins before neoadjuvant therapy, using pretreatment tumor size/stage as exclusion criteria, and specifically stating lateral excision margins. Where detailed, the majority of local recurrences occurred in patients with clear pathological margins, yet significant variation existed for pathological assessment and reporting, with few studies detailing R status and some not reporting margin status at all. Significant variability also existed for adverse tumor features that mandated completion surgery, and, importantly, many series describe patients refusing completion surgery where indicated. LIMITATIONS: We were unable to perform meta-analysis because studies lacked sufficient methodologic homogeneity to synthesize. CONCLUSIONS: The observations from this study prompt additional study, standardization of technique, and cautious use of local excision of rectal cancer in the setting of neoadjuvant chemoradiotherapy.

Avoiding Radical Surgery in Elderly Patients With Rectal Cancer Is Cost-Effective.

BACKGROUND: Radical surgery is associated with significant perioperative mortality in elderly and comorbid populations. Emerging data suggest for patients with a clinical complete response after neoadjuvant chemoradiotherapy that a watch-and-wait approach may provide equivalent survival and oncological outcomes. OBJECTIVE: The purpose of this study was to compare the cost-effectiveness of watch and wait and radical surgery for patients with rectal cancer after a clinical complete response following chemoradiotherapy. DESIGN: Decision analytical modeling and a Markov simulation were used to model long-term costs, quality-adjusted life-years, and cost-effectiveness after watch and wait and radical surgery. Sensitivity analysis was used to investigate the effect of uncertainty in model parameters. SETTINGS: A third-party payer perspective was adopted. PATIENTS: Patients included in the study were a 60-year-old male cohort with no comorbidities, 80-year-old male cohorts with no comorbidities, and 80-year-old male cohorts with significant comorbidities. INTERVENTIONS: Radical surgery and watch-and-wait approaches were studied. MAIN OUTCOME MEASURES: Incremental cost, effectiveness, and cost-effectiveness ratio over the entire lifetime of the hypothetical patient cohorts were measured. RESULTS: Watch and wait was more effective (60-year-old male cohort with no comorbidities = 0.63 quality-adjusted life-years (95% CI, 2.48-3.65 quality-adjusted life-years); 80-year-old male cohort with no comorbidities = 0.56 quality-adjusted life-years (95% CI, 0.52-1.59 quality-adjusted life-years); 80-year-old male cohort with significant comorbidities = 0.72 quality-adjusted life-years (95% CI, 0.34-1.76 quality-adjusted life-years)) and less costly (60-year-old male cohort with no comorbidities = $11,332.35 (95% CI, $668.50-$23,970.20); 80-year-old male cohort with no comorbidities = $8783.93 (95% CI, $2504.26-$21,900.66); 80-year-old male cohort with significant comorbidities = $10,206.01 (95% CI, $2762.014-$24,135.31)) independent of patient cohort age and comorbidity. Consequently, watch and wait was more cost-effective with a high degree of certainty (range, 69.6%-89.2%) at a threshold of $50,000/quality-adjusted life-year. LIMITATIONS: Long-term outcomes were derived from modeled cohorts. Analysis was performed for a United Kingdom third-party payer perspective, limiting generalizability to other healthcare contexts. CONCLUSIONS: Watch and wait is likely to be cost-effective compared with radical surgery. These findings strongly support the discussion of organ-preserving strategies with suitable patients.

Avoiding radical surgery improves early survival in elderly patients with rectal cancer, demonstrating complete clinical response after neoadjuvant therapy: results of a decision-analytic model.

BACKGROUND: In elderly and comorbid patients with rectal cancer, radical surgery is associated with significant perioperative mortality. Data suggest that a watch-and-wait approach where a complete clinical response is obtained after neoadjuvant chemoradiotherapy might be oncologically safe. OBJECTIVE: This study aimed to determine whether patient age and comorbidity should influence surgeon and patient decision making where a complete clinical response is obtained. DESIGN: Decision-analytic modeling consisting of a decision tree and Markov chain simulation was used. Modeled outcome parameters were elicited both from comprehensive literature review and from a national patient outcomes database. SETTINGS: Outcomes for 3 patient cohorts treated with neoadjuvant therapy were modeled after either surgery or watch and wait. PATIENTS: Patients included 60-year-old and 80-year-old men with mild comorbidities (Charlson score <3) and 80-year-old men with significant comorbidities (Charlson score >3). MAIN OUTCOME MEASURES: Absolute survival, disease-free survival, and quality-adjusted life years were measured. RESULTS: The model found that absolute survival was similar in 60-year-old patients but was significantly improved in fit and comorbid 80-year-old patients at 1 year after treatment where watch and wait was implemented instead of radical surgery, with a survival advantage of 10.1% (95% CI, 7.9-12.6) and 13.5% (95% CI, 10.2-16.9). At all of the other time points, absolute survival was equivalent for both techniques. There were no short- or long-term differences among any patient groups managed either by radical surgery or watch and wait in terms of either disease-free survival or quality-adjusted life years. LIMITATIONS: Oncologic data for the watch-and-wait approach used for this study is derived from only a small number of studies pertaining to a highly selected group of patients. The 90-day postoperative mortality rate derived from the United Kingdom population-based study might be lower in other countries or individual institutions. CONCLUSIONS: This study suggests competing effects of oncologic and surgical risk when using watch-and-wait management and that elderly and comorbid patients have the most to gain from this approach.

Sentinel nodes are identifiable in formalin-fixed specimens after surgeon-performed ex vivo sentinel lymph node mapping in colorectal cancer.

BACKGROUND: In recent years, the technique of sentinel lymph node (SLN) mapping has been applied to colorectal cancer. One aim was to ultrastage patients who were deemed node negative by routine pathologic processing but who went on to develop systemic disease. Such a group may benefit from adjuvant chemotherapy. METHODS: With fully informed consent and ethical approval, 37 patients with primary colorectal cancer and 3 patients with large adenomas were prospectively mapped. Isosulfan blue dye (1 to 2 mL) was injected around tumors within 5 to 10 minutes of resection. After gentle massage to recreate in vivo lymph flow, specimens were placed directly into formalin. During routine pathologic analysis, all nodes were bivalved, and blue-staining nodes were noted. These later underwent multilevel step sectioning with hematoxylin and eosin and cytokeratin staining. RESULTS: SLNs were found in 39 of 40 patients (98% sensitivity), with an average of 4.1 SLNs per patient (range, 1-8). In 14 of 16 (88% specificity) patients with nodal metastases on routine reporting, SLN status was in accordance. Focused examination of SLNs identified occult tumor deposits in 6 (29%) of 21 node-negative patients. No metastatic cells were found in SLNs draining the three adenomas. CONCLUSIONS: The ability to identify SLNs after formalin fixation increases the ease and applicability of SLN mapping in colorectal cancer. Furthermore, the sensitivity and specificity of this simple ex vivo method for establishing regional lymph node status were directly comparable to those in previously published reports.