Actuarial Local Recurrence Rate Research Articles

The percentage of mesorectal infiltration as a prognostic factor after curative surgery for pT3 rectal cancer.

The aim of this study is to evaluate the prognostic value of a novel variable - the percentage of mesorectal infiltration (PMI) - in pT3 rectal cancer. A cohort of 241 patients with pT3 rectal adenocarcinoma, operated on between February 2002 and May 2019, was selected for the analysis. Data concerning patient, treatment and tumour characteristics were collected. The depth of mesorectal infiltration (DMI) and the distance between the deepest invasion and the circumferential resection margin (CRM) were measured. The PMI was calculated using a formula combining these parameters. Neoadjuvant therapy was administered in 33.2% of cases. A complete mesorectal excision was achieved in 74% of patients. The CRM was affected in 24 patients (9.9%). The 5-year actuarial local recurrence (LR), overall recurrence (OR) and overall survival (OS) rates were 7.5%, 22.9% and 72.4%, respectively. The PMI was significantly associated with worse oncological outcomes regarding LR (p= 0.009), OR (p= 0.001) and OS (p= 0.016) rates. A cut-off value of PMI >60% had the highest specificity (80%) for LR (p= 0.026), OR (p= 0.04) and OS (p= 0.07). The PMI has an adverse prognostic impact on the oncological results following surgery for pT3 rectal cancer. It allows prediction of the risk of both LR and distant recurrence with higher accuracy than the DMI or the distance to the CRM. A PMI >60% may be used as a cut off value while subclassifying pT3 rectal tumours. It may influence decision-making while establishing adjuvant treatment and the follow-up schedule.

Impact of a multidisciplinary training programme on outcome of upper rectal cancer by critical appraisal of the extent of mesorectal excision with postoperative MRI.

BackgroundOptimal management of patients with upper rectal cancer remains unclear. Partial mesorectal excision (PME) without neoadjuvant therapy is currently advocated for the majority of patients. Recent studies, however, reported a high risk of local recurrence and suboptimal surgery. The aim of this study was to evaluate the effects of a quality assurance initiative with postoperative MRI to improve outcomes in these patients.MethodsPatients who underwent mesorectal excision with curative intent for rectal cancer in 2007–2013 were included. Postoperative MRI of the pelvis was performed 1 year after surgery. In 2011, a multidisciplinary workshop with focus on extent and completeness of surgery was held for training surgeons, pathologists and radiologists involved in treatment planning. Images of residual mesorectum and histopathological reports were reviewed with regard to the distal resection margin. Local recurrence after a minimum of 3 years' follow‐up was compared between two cohorts from 2007–2010 and 2011–2013.ResultsA total of 627 patients were included; postoperative MRI of the pelvis was done in 381 patients. The 3‐year actuarial local recurrence rate in patients with upper rectal cancer improved from 12·9 to 5·0 per cent (P = 0·012). After the workshop, fewer patients with cancer of the upper rectum were selected to have PME (90·8 per cent in 2007–2010 versus 80·2 per cent in 2011–2013; P = 0·023), and fewer patients who underwent PME had an insufficient distal resection margin (61·7 versus 31 per cent respectively; P < 0·001).ConclusionQuality assessment of surgical practice may have a major impact on oncological outcome after surgery for upper rectal cancer.

Results of a Phase 1/2 Trial of Chemoradiotherapy With Simultaneous Integrated Boost of Radiotherapy Dose in Unresectable Locally Advanced Esophageal Cancer

Effective treatment options for locally advanced esophageal cancer are limited, and rates of local recurrence after standard chemoradiotherapy remain high. To evaluate toxic effects, local control, and overall survival rates after chemoradiotherapy with a simultaneous integrated boost of radiotherapy dose to the gross tumor and nodal disease for patients with unresectable locally advanced esophageal cancer. A phase 1/2, single-arm trial was conducted in 46 patients from April 28, 2010, to April 9, 2015 (median follow-up, 52 months [range, 2-86 months]), at a tertiary academic cancer center. Outcomes of the study patients were compared with those of 97 similar patients treated at the same institution from January 10, 2010, to December 5, 2014, as part of the interim analysis. Statistical analysis was performed from December 15, 2018, to February 12, 2019. Chemoradiotherapy with a simultaneous integrated boost of radiotherapy dose (50.4 Gy to subclinical areas at risk and 63.0 Gy to the gross tumor and involved nodes, all given in 28 fractions) with concurrent docetaxel and capecitabine or fluorouracil. Toxic effects, local (in-field) control, and overall survival rates. All 46 patients (11 women and 35 men; median age, 65.5 years [range, 37.3-84.4 years]) received per-protocol therapy, as intensity-modulated photon therapy (39 [85%]) or intensity-modulated proton therapy (7 [15%]); 11 patients (24%) ultimately underwent resection. No patients experienced grade 4 or 5 toxic effects; the 10 acute grade 3 toxic events were esophagitis (4), dysphagia (3), and anorexia (3) and the 3 late grade 3 toxic events were all esophageal strictures. The actuarial local recurrence rates were 22% (95% CI, 11%-35%) at 6 months, 30% (95% CI, 18%-44%) at 1 year, and 33% (95% CI, 20%-46%) at 2 years. Overall, 15 patients (33%) experienced local failure, at a median interval of 5 months (range, 1-24 months). The median overall survival time was 21.5 months (range, 2.3-86.4 months). Exploratory comparison with a 97-patient contemporaneous institutional cohort receiving standard-dose (non-simultaneous integrated boost) chemoradiotherapy showed superior local control (hazard ratio, 0.49; 95% CI, 0.26-0.92; P = .03) and overall survival (hazard ratio, 0.66; 95% CI, 0.47-0.94; P = .02) in the group that received chemoradiotherapy with a simultaneous integrated boost. These findings suggest that chemoradiotherapy with a simultaneous integrated boost of radiotherapy dose for locally advanced esophageal cancer is well tolerated, with encouraging local control, and thus warrants further study. ClinicalTrials.gov identifier: NCT01102088.

Margin status revisited in vulvar squamous cell carcinoma

ObjectiveTo determine the incidence of local recurrence of vulvar squamous cell carcinoma in relation to tumor- and/or precursor lesion free pathologic margins. MethodsConsecutive patients with primary vulvar squamous cell carcinoma surgically treated in two Dutch expert centers between 2000 and 2010 were included. All pathology slides were independently reviewed by two expert gynecopathologists, and local recurrence was defined as any recurrent disease located on the vulva. Time to first local recurrence was compared for different subgroups using univariable and multivariable Cox-regression analyses. ResultsIn total 287 patients with a median follow-up of 80months (range 0–204) were analyzed. The actuarial local recurrence rate ten years after treatment was 42.5%. Pathologic tumor free margin distance did not influence the risk on local recurrence (HR 1.03 (95% CI 0.99–1.06)), neither using a cutoff of eight, five, or three millimeters. Multivariable analyses showed a higher local recurrence rate in patients with dVIN and LS in the margin (HR 2.76 (95% CI 1.62–4.71)), in patients with dVIN in the margin (HR 2.14 (95% CI 1.11–4.12)), and a FIGO stage II or higher (HR 1.62 (95% CI 1.05–2.48)). ConclusionsLocal recurrences frequently occur in patients with primary vulvar carcinoma and are associated with dVIN (with or without LS) in the pathologic margin rather than any tumor free margin distance. Our results should lead to increased awareness among physicians of an ongoing risk for local recurrence and need for life-long follow-up. Intensified follow-up and treatment protocols for patients with dVIN in the margin should be evaluated in future research.

Long-term survival and late complications of intensity-modulated radiotherapy for recurrent nasopharyngeal carcinoma

BackgroundTo evaluate the effectiveness and toxicities of intensity-modulated radiotherapy (IMRT) for locally recurrent nasopharyngeal carcinoma (NPC).MethodsOne hundred and eighty-four previously irradiated NPC patients with recurrent disease and re-irradiated by IMRT between February 2005 to May 2013 had been reviewed. The disease was re-staged I in 33, II in 27, III in 70 and IV in 54 patients. Seventy-five percent of the patients received cisplatin-based chemotherapy.ResultsThe median survival time was 33 months. The 3-year actuarial rates of local recurrence–free survival (LRFS), distant metastases–free survival (DMFS), and overall survival (OS) rates were 85.1, 91.1, and 46.0%, respectively. About 53% of the patients experienced Grade 3–4 late toxicities. Forty-four patients died of massive hemorrhage of the nasopharynx caused by radiation induced mucosal necrosis. Multivariate analysis indicated that chemotherapy and time interval between initial radiotherapy and re-irradiation were independent predictors for DMFS.ConclusionIMRT is an effective method for patients with locally recurrent NPC. Massive hemorrhage of the nasopharynx is the major sever late complication and also the leading cause of death. Early recurrence is negative factor for DMFS. Combination of chemotherapy can improve DMFS, but not for OS. Optimal salvage treatment strategies focusing on improvement of survival and minimization of late toxicities are warranted.

Long-Term Survival and Late Complications of Intensity-Modulated Radiation Therapy for Recurrent Nasopharyngeal Carcinoma

To evaluate the effectiveness and toxicities of intensity-modulated radiotherapy (IMRT) for locally recurrent nasopharyngeal carcinoma (NPC). One hundred eighty-four previously irradiated NPC patients with recurrent disease and re-irradiated by IMRT between February 2005 to May 2013 had been reviewed. The disease was re-staged I in 33, II in 27, III in 70 and IV in 54 patients. Seventy-five percent of the patients received cisplatin-based chemotherapy. The median survival time was 33 months. The 5-year actuarial rates of local recurrence–free survival (LRFS), distant metastases–free survival (DMFS), and overall survival (OS) rates were 71.7%, 85.9%, and 28.8%, respectively. About 53% of the patients experienced Grade 3-4 late toxicities. Forty-four patients died of massive hemorrhage of the nasopharynx caused by radiation induced mucosal necrosis. Multivariate analysis indicated that chemotherapy and time interval between initial radiotherapy and re-irradiation were independent predictors for DMFS. IMRT is an effective method for patients with locally recurrent NPC. Massive hemorrhage of the nasopharynx is the major sever late complication and also the leading cause of death. Early recurrence is negative factor for DMFS. Combination of chemotherapy can improve DMFS, but not for OS. Optimal salvage treatment strategies focusing on improvement of survival and minimization of late toxicities are warranted.

Carcinoembryonic antigen as a marker of radioresistance in colorectal cancer: a potential role of macrophages

BackgroundWe sought to identify the carcinoembryonic antigen (CEA) as a marker of radioresistance in rectal cancer.MethodsFrom July 1997 to January 2008, 104 patients with stage II or III rectal cancer who were treated with post-operative radiotherapy (PORT) were included in this study. The doses of radiotherapy ranged from 45 to 54.6 Gy. The CEA levels were measured before surgery. We analyzed the actuarial rates of overall survival (OS), distant metastasis (DM), and local recurrence (LR) using Kaplan-Meier curves. Multivariate analyses were performed with Cox regression models. We used THP-1 monocyte cell lines for macrophage differentiation (M0, M1 or M2). The RNA extracted from the macrophages was analyzed via a genomic method in the core laboratory. The radiosensitivities of CEA-rich LS1034 cells were compared between cells with and without the conditioned media from CEA-stimulated macrophages.ResultsPreoperative CEA levels ≥10 ng/mL were independent predictive factors for OS (p = 0.005), DM (p = 0.026), and LR (p = 0.004). The OS rates among the patients with pretreatment CEA levels < 10 ng/mL and ≥10 ng/mL were 64.5% and 35.9% (p = 0.004), respectively. The corresponding rates of DM were 40.6% and 73.1% (p = 0.024). The corresponding rates of LR were 6.6% and 33.9% (p = 0.002). In the M0 macrophages, exogenous CEA elicited a dose-response relationship with M2 differentiation. In the CEA-stimulated M0 cells, some mRNAs were upregulated by as much as 5-fold, including MMP12, GDF15, and JAG1. In the CEA-stimulated M2 cells, a 4-fold up-regulation of GADD45G mRNA was noted. The conditioned media from the CEA-stimulated M2 cells elicited an increase in the numbers of LS180, SW620, and LS1034 cells after irradiation. CEA caused the M2 differentiation of the macrophages.ConclusionPretreatment CEA levels ≥10 ng/mL are a significant risk factor for OS, DM, and LR following PORT for rectal cancer. CEA causes radioresistance in the presence of M2 macrophages. More comprehensive examinations prior to surgery and intensive adjuvant therapy are suggested for patients with CEA levels ≥10 ng/mL. Further studies of these mechanisms are needed.

The Role of Pathological Margin Distance and Prognostic Factors After Primary Surgery in Squamous Cell Carcinoma of the Vulva.

The aim of this study was to determine the impact of clear surgical margin distance and other factors associated with the recurrence and survival of patients with squamous cell carcinoma of the vulva. A total of 107 patients operated for vulvar carcinoma from 1996 to 2016 were included in the analysis. Patients were divided into subgroups with clear pathological margin of 2 mm or less, greater than 2 to less than 8 mm, and 8 mm or greater for the analysis of the prognostic impact of the clear margin distance. Data were analyzed using the Kaplan-Meier method and Cox proportional hazards regression. The median age of the patients was 66 years. The median follow-up was 69 months. The labia majora and/or labia minora were the most common sites of involvement. Radical local excision and radical vulvectomy were performed in 96 and 11 patients, respectively. Thirty-nine patients received adjuvant radiotherapy. The overall recurrence rate was 46%. At 231 months, the actuarial local recurrence rate was 18.6%. Patients with clear pathological margin of 2 mm or less had significantly higher local recurrence risk. Five-year disease-free survival was 32.7%. Older age and adjuvant chemotherapy were found as independent prognostic factors for disease-free survival. Our data suggest that a more than 2 mm tumor-free margins is associated with better local control. In addition, older age is an independent prognostic factor for survival.

Second breast conserving surgery and interstitial radiotherapy for the treatment of breast tumor local recurrences. Five-year results

To report the clinical outcomes of second breast-conserving therapy with perioperative interstitial radiotherapy for the treatment of ipsilateral breast tumor recurrences. Between 1999 and 2015, 33 patients, presenting with an ipsilateral breast tumor recurrence after previous breast conserving therapy, were salvaged by re-excision and perioperative high-dose-rate interstitial brachytherapy. A median of 8 (range: 4-24) catheters were implanted into the tumor bed intraoperatively. A total dose of 22 Gy in 5 fractions of 4.4 Gy was delivered to the tumor bed with a margin of 1-2 cm, on 3 consecutive days. The adjuvant systemic treatments consisted of hormonal therapy for 24 patients (73%) and chemotherapy for 6 patients (18%). The survival results were estimated by the Kaplan-Meier method. Late side effects and cosmetic results were also registered. The median follow-up time following the second breast conserving therapy was 61 months (range: 26-189 months). During the follow-up, 4 patients (12.1%) developed second local recurrence. The five-year actuarial rates of the second local, regional and distant recurrence were 6.3%, 6.1%, and 14.9%, respectively. The five-year probabilities of disease-free, cancer-specific and overall survival were 76.2%, 92.4%, and 89.2%, respectively. Four (12%), 19 (58%), 4 (12%) and 6 (18%) patients had excellent, good, fair and poor cosmetic results, respectively. Grade 2 and 3 fibrosis developed in 9 (27%) and 1 (3%) patients. Asymptomatic fat necrosis was detected in 7 (21%) women. Second breast conserving therapy with perioperative high-dose-rate interstitial brachytherapy is a safe and feasible option for the management of ipsilateral breast tumor recurrences. Interstitial brachytherapy may decrease the risk of second local relapse with acceptable cosmetic results and low rate of late side effects. Hence, in selected cases it can provide a feasible alternative to salvage mastectomy. Orv Hetil. 2018; 159(11): 430-438.

Abstract P3-13-05: Long-term outcome of neoadjuvant endocrine therapy followed by breast conserving surgery

Abstract Background:Neoadjuvant therapy (NET) in women with large or locally advanced estrogen receptor(ER)-rich breast cancers (BC) allows the option of breast-conserving surgery (BCS) + radiotherapy (RT). The aim was to study the long term safety of this strategy. Methods: 280 postmenopausal women (median age 77, range 50-95, table 1) with ER-rich BC had BCS after NET (median duration 4.8 mths, range 1.7-42.8 mths). 221 (79%) received only letrozole. 59 (21%) began on letrozole and were switched to anastrozole, exemestane or tamoxifen due to adverse events or lack of clinical response. 200 patients (71%) had adjuvant RT (RTgroup) and 25 (9%), adjuvant chemotherapy. Median follow-up = 5.5 years. Table 1: Clinical characteristics of patients.CharacteristicNo. PatientsTumour SizeT131 (11%)T2169 (60%)T314 (5%)T456 (20%)Unknown10 (4%)Grade136 (13%)2153 (55%)370 (25%)Unknown21 (7%)Nodes+ve101 (36%)-ve177 (63%)Unknown3 (1%)ER Allred615 (5%)762 (22%)8203 (73%) Results: 254 patients had NET response data. 74% had a clinical response. NET response was higher for grade 1 (84%) than for 2 (73%) or 3 (72%) cancers. Actuarial local recurrence rates (LRR) were 8% (95%CI±0.04) and 12% (95%CI±0.06) at 5 &amp; 10 years. Actuarial overall BC recurrence rates were 14% (95%CI±0.04) and 27% (95%CI±0.12) at 5 &amp; 10 years, with BCS death rates of 7% (95%CI±0.04) and 14% (95%CI±0.10) at 5 &amp; 10 years, showing only half with recurrence died from BC. Crude all-cause mortality but not BC-specific survival (BCSS) favoured those who had adjuvant RT (P&amp;lt;0.001) or chemotherapy (P=0.006). The 15-year rate was 50.9%, while BCS death rate was only 7.3%. Positive nodes were associated with worse overall recurrence free survival (RFS) (P=0.007) but not local RFS or BCSS. Tumour size was not associated with RFS or BCSS. Tumour grade was not associated with RFS but grade 3 patients had a lower BCSS (P=0.002) compared to patients grade 1/2 cancers. RT was associated with improved LRR (P&amp;lt;0.0001) and overall RR (P=0.038): 5 &amp; 10 year in RTgroup were 5% (95%CI±0.04) + 7% (95%CI±0.04) vs 9% (95%CI±0.12) + 31% (95%CI±0.24) in no-RTgroup. The 5 &amp; 10 year ORR in the RTgroup was 14% (95%CI±0.06) and 39% (95%CI±0.16) vs 28% (95%CI±0.16) + 38% (95%CI±0.24) in the no-RTgroup. Although differences were not significant, BCSS was higher in the no-RTgroup: 5 &amp; 10 yearly BCSS rates were 10% (95%CI±0.04) and 20% (95%CI±0.12) vs 6% (95%CI±0.08) + 12% (95%CI±0.14) in RTgroup. 16/67 patients with T3/4 cancers with no RT had lower overall RFS (P=0.018) but no difference in local RFS. 13/98 patients with node +ve disease with no RT had lower LRR (P=0.002) and overall RR (P=0.024). 54/169 node -ve patients with no RT had lower LRR (P=0.019) but similar overall RR. 50/183 patients with grade 1/2 cancers had no RT and had lower LRR (P&amp;lt;0.0001) and overall RR (P=0.049). BCSS was not associated with RT use in subgroups related to tumour size, node status or grade. Discussion: · Response to NET is not worse in ER rich grade 3 or node positive cancers. · After NET, BCS and RT provides excellent LRR. · BCSS rates were low; most died of other causes. · NET followed by BCS and RT is safe even for grade 3 and node positive cancers. · BCS alone provides adequate disease control for majority with significant co-morbidities. Citation Format: Yau JD, Turnbull AK, Renshaw L, Keys J, Leeper A, Thomas JS, Dixon JM. Long-term outcome of neoadjuvant endocrine therapy followed by breast conserving surgery [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-13-05.

A Retrospective Long-term Follow-up Study of Stereotactic Body Radiation Therapy for Non-Small Cell Lung Cancer From a Single Institution: Incidence of Late Local Recurrence

To assess the local recurrence (LR) rate and timing after stereotactic body radiation therapy (SBRT) for non-small cell lung cancer using long-term follow-up data from a single institution. Patients with primary or recurrent non-small cell lung cancer with or without pathologic verification, with tumors <3cm, treated with SBRT (isocenter prescription of 48Gy in 4 fractions) between April 1998 and August 2014, and with >6months' follow-up were eligible. The LR rate was calculated by the cumulative incidence function, accounting for death as a competing risk. Univariate and multivariate analyses were performed to identify prognostic factors for LR. A total of 216 patients and 230 tumors were analyzed. The median follow-up time of tumors without LR was 3.9years, and the crude number of LR cases was 49 (21%). The actuarial rate of LR was 19% (95% confidence interval, 14%-25%) at 5years. The number of LR cases in each period was 10 in year 1, 17 in year 2, 9 in year 3, 3 in year 4, 3 in year 5, and 7 after 5years. Among 73 tumors with >5years' follow-up, we observed 7 late LRs. The tumor histology of these late LRs was adenocarcinoma in 3, squamous cell carcinoma in 2, and unknown in 2 (1 of the unknown cases was confirmed as adenocarcinoma following salvage surgery). The median time to LR was 2.1years (interquartile range, 1.5-4.2years) for adenocarcinoma compared with 1.3years (interquartile range, 1.0-2.3years) for squamous cell carcinoma.Multivariate analysis revealed that larger tumor size, squamous cell histology compared with adenocarcinoma, and use of abdominal compression for respiratory motion management were independent negative prognostic factors for LR. Long-term follow-up data demonstrated that late LR was not uncommon and that careful follow-up after SBRT is needed, especially in patients with adenocarcinoma.

Composite PEEK/Carbon fiber implants can increase the effectiveness of radiotherapy in the management of spine tumors.

Combination of surgery and radiotherapy in the treatment of primary spine tumour can be indicated in some cases where a satisfactory oncological margin cannot be achieved. The presence of metal hardware has always limited post-operative radiotherapy due to the scattering effects of ionizing radiation or particles. The use of a fixation system (including rods and screw) fully made in PEEK embedded Carbon fiber (CFR-PEEK) could make easier and more effective the post-operative radiotherapy as it is radiolucent and does not interfere with ionizing radiation and accelerated particles. An ambispective study was performed on the first 22 consecutive primary tumor patients, who underwent spinal surgery including a composite CFR-PEEK fixation system. Oncologic surgery was palliative decompression and fixation in 3 cases; tumor excision in 15; en bloc resection in 4. The incidence of complications (intra- and postoperative), local control (LC) and local recurrence (LR), and changes in neurological status were considered. Only one intraoperative screw breakage occurred and one case of loosening of sacral screws were found at 12 months in one patient. No rod breakage, neither any screw/rod disconnection was found. Post-operative RT has been performed in 19 patients. The overall number of progression of the tumour or LR was 7. The actuarial rate of LR or progression of the tumour, calculated according to the Kaplan-Meier method, was 17.6% at 12 months. The CFR-PEEK fixation system is comparable to standard titanium system in term of intraoperative complications, stability at weight bearing and at functional recovery. Thanks to radiolucency CFR-PEEK stabilization devices are more suitable in patients eligible for RT: the absence of image artifacts together with significantly less dose perturbation improve the treatment accuracy. Moreover the radiolucency is useful in the follow-up of patients thus allowing early detection of LR.

A Pilot Study Evaluating the Use of Dynamic Contrast-Enhanced Perfusion MRI to Predict Local Recurrence After Radiosurgery on Spinal Metastases.

Purpose:Dynamic contrast-enhanced magnetic resonance imaging offers noninvasive characterization of the vascular microenvironment and hemodynamics. Stereotactic radiosurgery, or stereotactic body radiation therapy, engages a vascular component of the tumor response which may be detectable using dynamic contrast-enhanced magnetic resonance imaging. The purpose of this study is to examine whether dynamic contrast-enhanced magnetic resonance imaging can be used to predict local tumor recurrence in patients with spinal bone metastases who undergo high-dose radiotherapy with stereotactic radiosurgery.Materials and Methods:We conducted a study of 30 patients with spinal metastases who underwent dynamic contrast-enhanced magnetic resonance imaging before and after radiotherapy. Twenty patients received single-fraction stereotactic radiosurgery (24 Gy), while 10 received hypofractionated stereotactic radiosurgery (3-5 fractions, 27-30 Gy total). Kaplan-Meier analysis was used to estimate the actuarial local recurrence rates. Two perfusion parameters (Ktrans: permeability and Vp: plasma volume) were measured for each metastasis. Percentage change in parameter values from pre- to posttreatment was calculated and compared.Results:At 20-month median follow-up, 5 of the 30 patients had pathological evidence of local recurrence. One- and 3-year actuarial local recurrence rates were 24% and 44% for the hypofractionated stereotactic radiosurgery cohort versus 5% and 16% for the single-fraction stereotactic radiosurgery cohort (P = .20). The average change in Vp and Ktrans for patients without local recurrence versus those with local recurrence was −76% and −66% versus +28% and −14% (P < .01 for both). With a cutoff point of −20%, Vp had a sensitivity, specificity, positive predictive value, and negative predictive value of 100%, 98%, 91%, and 100%, respectively, for the detection of local recurrence following high-dose radiotherapy. Using this definition, dynamic contrast-enhanced magnetic resonance imaging identified local recurrence up to 18 months (mean [standard deviation], 6.6 [6.8] months) earlier than standard magnetic resonance imaging.Conclusions:We demonstrated that changes in perfusion parameters, particularly Vp, after high-dose radiotherapy to spinal bone metastases were predictive of local tumor recurrence. These changes predicted local recurrence on average >6 months earlier than standard imaging did.

Does adjuvant radiation therapy benefit women with small mammography-detected breast cancers?

Women with small nonpalpable breast tumours have an excellent prognosis. The benefit of radiotherapy in this group of low-risk women is unknown. A cohort of 1595 women with stages i-iii invasive breast cancer treated with breast-conserving surgery were followed for local recurrence. Using t-tests, baseline demographic data and tumour characteristics were compared for the women who had palpable (n = 1023) and mammography-detected (n = 572) breast cancers. The 15-year actuarial risk of local recurrence was estimated using a Kaplan-Meier method, stratified for adjuvant radiation therapy (yes or no), tumour palpability (palpable or not), and tumour size (≤1 cm or >1 cm). Hazard ratios (hrs) and 95% confidence intervals (95% cis) were calculated using a multivariate Cox regression model. Results were considered statistically significant if 2-tailed p values were less than 0.05. Among women with a nonpalpable tumour, the 15-year actuarial rates of local recurrence were, respectively, 13.9% and 18.3% for those treated and not treated with adjuvant radiation therapy (hr: 0.65; 95%ci: 0.40 to 1.06; p = 0.08). Among women with small nonpalpable breast cancers (≤1.0 cm), the rates were 14.6% and 13.4% respectively (p = 0.67). The absolute reduction in 15-year local recurrence was 11.0% for women with palpable tumours. Our results suggest that women with small (<1 cm) screen-detected nonpalpable breast cancers likely derive little benefit from adjuvant radiotherapy; however, an adequately powered randomized trial would be required to make definitive conclusions.

Primary Extremity Soft Tissue Sarcomas: Does Local Control Impact Survival?

The objective of this study was to evaluate the adequate margin in the local treatment of extremity soft tissue sarcomas (ESTS) and understand the relationship between local control and overall survival (OS). All consecutive patients treated for a primary ESTS at a single center from 1993 to 2012 were reviewed. In all, 531 patients were included. Twelve (2%) underwent a first-line amputation. The resections were R0/R1/not available in 434 (82%), 92 (17%), and 5 patients (1%). The median tumor size was 8cm, and the tumor grades were 1 (n=132), 2 (n=201), and 3 (n=195). The median size of the minimal margin was 2mm on fixed specimen. Preop or postop chemotherapy was administered to 222 patients, and 414 received radiotherapy. With a median follow-up period of 7 years, the 5-year actuarial local recurrence (LR) rate and OS were 8% (95% CI, 6-11%) and 80% (95% CI, 76-83%). Predictors of worse OS were grade 3, leiomyosarcoma, male gender, and age >60 years, whereas tumor size, margin status, and LR were not. Among patients requiring re-excision (n=252), the presence of residual cells correlated with OS but not LR. After preoperative treatment, a percentage of residual cells ≥10% correlated with OS but not LR. In the multivariate analysis, specific subtypes (epithelioid sarcoma and myxofibrosarcoma) and margin size <1mm correlated with LR, whereas grade and the tissue constituting the surgical margins did not. Specific subtypes and surgical margin size <1mm were correlated with a higher LR. Neither the margin status nor LR affect OS.

Locally Advanced Rectal Cancer: Preliminary Results of Rectal Preservation After Neoadjuvant Chemoradiotherapy

IntroductionThe standard treatment for locally advanced rectal cancer is total mesorectal excision. However, organ preservation has been proposed for tumours with good response to neoadjuvant treatment. The aim of this study was to evaluate the oncologic results of this strategy. MethodsThis is a retrospective cohort study (2005–2014) including a consecutive series of patients with rectal adenocarcinoma with complete or almost complete clinical response after preoperative chemo-radiotherapy, that were treated according to a strategy of preservation of the rectum. ResultsA total of 204 patients with rectal cancer received neoadjuvant therapy. Thirty (14.7%) had a good response and were treated with rectal preservation (23 “Watch and wait” and 7 local resections). Median follow-up was 46 months (interquartile range: 30–68). In the group of “Watch & Wait”, 4 patients had local recurrence before 12 months (actuarial local recurrence rate=18.5%). All of them underwent salvage surgery (2 with radical surgery and 2 local resections) without any further recurrence. Disease-free survival actuarial rate at 3 years follow-up was 94.1% (95% CI 82.9–100). None of the 7 patients that were treated by local excision had local recurrence. The organ preservation rate for the whole group was 93%. ConclusionThe strategy of organ preservation in locally advanced rectal cancer is feasible in cases with good response to neoadjuvant therapy. When implemented in a highly selected group of patients this strategy is associated with satisfactory oncologic results.

Cáncer de recto localmente avanzado: resultados preliminares de la preservación del recto después de quimiorradioterapia neoadyuvante

IntroductionThe standard treatment for locally advanced rectal cancer is total mesorectal excision. However, organ preservation has been proposed for tumors with good response to neoadjuvant treatment. The aim of this study was to evaluate the oncologic results of this strategy. MethodsThis is a retrospective cohort study (2005-2014) including a consecutive series of patients with rectal adenocarcinoma with complete or almost complete clinical response after preoperative chemo-radiotherapy, that were treated according to a strategy of preservation of the rectum. ResultsA total of 204 patients with rectal cancer received neoadjuvant therapy. Thirty (14.7%) had a good response and were treated with rectal preservation (23 «Watch and Wait» and 7 local resections). Median follow-up was 46 months (interquartile range: 30-68). In the group of «Watch & Wait», 4 patients had local recurrence before 12 months (actuarial local recurrence rate=18.5%). All of them underwent salvage surgery (2 with radical surgery and 2 local resections) without any further recurrence. Disease-free survival actuarial rate at 3 years follow-up was 94.1% (95% CI 82.9-100). None of the 7 patients that were treated by local excision had local recurrence. The organ preservation rate for the whole group was 93%. ConclusionThe strategy of organ preservation in locally advanced rectal cancer is feasible in cases with good response to neoadjuvant therapy. When implemented in a highly selected group of patients this strategy is associated with satisfactory oncologic results.

Oncologic Outcomes of Extended Robotic Resection for Rectal Cancer.

Surgery for locally advanced rectal cancers beyond the plane of total mesorectal excision (TME) or extramesorectal nodal involvement should include complete resection. This study evaluated the oncologic feasibility and safety of robot-assisted surgery for rectal cancer beyond the TME plane. The study analyzed the operative, perioperative, and oncologic outcomes for all patients who underwent robot-assisted extended rectal cancer surgery from April 2009 to February 2015. Of 36 patients, 22 underwent multivisceral en bloc resection, and 18 underwent extramesorectal lymph node (EMRLN) dissection. The median tumor location was 5cm [interquartile range (IQR), 2.2-9.0cm] from the anal verge. A total of 32 patients underwent neoadjuvant chemoradiation therapy. The median body mass index of the patients was 26.8kg/m(2) (IQR, 24.0-31.9kg/m(2)). Conversion was required for one patient because of inability to tolerate the Trendelenburg position. All the resections were R0, and there were no incomplete TMEs. The vagina and prostate or periprostatic structures were the most commonly resected (n=13/22), and the lateral pelvic nodes were the most common EMRLNs (n=16/18). The median numbers of examined mesorectal lymph nodes and EMRLNs were respectively 20 (IQR, 18.0-28.0) and 2.5 (IQR, 1.0-6.0). The median hospital stay was 4days (IQR, 3.0-5.5days). Six patients experienced Clavien-Dindo grade 3 complications, the most common of which was deep abscess (n=5, 13.8%). The 5-year actuarial local recurrence rate was 3.6%. Minimally invasive resection for rectal cancer can be performed with extended lymph node dissection or en bloc multivisceral resection using the surgical robot in selected patients. This technique is feasible and has acceptable morbidity.

The relationship between local recurrence and death in early-stage breast cancer.

To examine the relationship between local recurrence and breast cancer mortality in women with early-stage breast cancer. We studied 1675 women with stage 0 (DCIS), stage I or stage II breast cancer who were treated with breast-conserving surgery at Women's College Hospital between 1987 and 2009. For each patient, we obtained information on age at diagnosis, tumour size, lymph node status, tumour grade, lymphovascular invasion, oestrogen receptor status, progesterone receptor status, HER2 status and treatments received (radiotherapy, chemotherapy and tamoxifen). Patients were followed from the date of diagnosis until local recurrence, death from breast cancer or the date of last follow-up. We used the Kaplan-Meier method to estimate 15-year local recurrence-free and breast cancer-specific survival rates for each stage at diagnosis. For each stage, the two rates were compared. After a mean follow-up of 13.1years, 243 women (14.5%) experienced a local recurrence and 281 women (16.8%) died of breast cancer. The 15-year actuarial rate of local recurrence was 16% for women with DCIS, 15% for women with stage I cancer and 16% for women with stage II cancer. The 15-year breast cancer-specific mortality rate was 3% for women with DCIS, 10% for women with stage I breast cancer and 30% for women with stage II breast cancer. After experiencing a local recurrence, the 15-year breast cancer mortality rate was 16% for women with DCIS, 32% for women with stage I breast cancer and 59% for women with stage II breast cancer. Across the spectrum of the early stages of breast cancer, the risk of local recurrence does not correlate with the risk of death from breast cancer. After local recurrence, the risk of death from breast cancer depends on the initial stage at diagnosis.

Selective approach for upper rectal cancer treatment: total mesorectal excision and preoperative chemoradiation are seldom necessary.

The implementation of preoperative chemoradiation combined with total mesorectal excision has reduced local recurrence rates in rectal cancer. However, the use of both types of treatment in upper rectal cancer is controversial. The purpose of this work was to assess oncological results after radical resection of upper rectal cancers compared with sigmoid, middle, and lower rectal cancers and to determine risk factors for local recurrence in upper rectal cancer. This was a retrospective analysis of prospectively collected data. This study was conducted in a tertiary care referral hospital in Valencia, Spain. Analysis included 1145 patients who underwent colorectal resection with primary curative intent for primary sigmoid (n = 450), rectosigmoid (n = 70), upper rectal (n = 178), middle rectal (n = 186), or lower rectal (n = 261) cancer. Oncological results, including local recurrence, disease-free survival, and cancer-specific survival, were compared between the different tumor locations. Univariate and multivariate analyses were performed to identify risk factors for local recurrence in upper rectal cancer. A total of 147 patients (82.6%) with upper rectal tumors underwent partial mesorectal excision, and only 10 patients (5.6%) of that group received preoperative chemoradiation. The 5-year actuarial local recurrence, disease-free survival, and cancer-specific survival rates for upper rectal tumors were 4.9%, 82.0%, and 91.6%. Local recurrence rates showed no differences when compared among all of the locations (p = 0.20), whereas disease-free survival and cancer-specific survival were shorter for lower rectal tumors (p = 0.006; p = 0.003). The only independent risk factor for local recurrence in upper rectal cancer was an involved circumferential resection margin at pathologic analysis (HR, 14.23 (95% CI, 2.75-73.71); p = 0.002). This was a single-institution, retrospective study. Most upper rectal tumors can be treated with partial mesorectal excision without the systematic use of preoperative chemoradiation. Involvement of the mesorectal fascia was the only independent risk factor for local recurrence in these tumors.