Simultaneous Distant Metastases Research Articles

169. PROPENSITY SCORE MATCHING ANALYSIS OF THE EFFECT ON PROGNOSIS OF PROPHYLACTIC NECK DISSECTION FOR ESOPHAGEAL CANCER

Abstract Background There is still no definite evidence regarding the prognostic effect of #104 prophylactic dissection. Materials and Methods: We conducted a retrospective study of patients who underwent esophagectomy regarding the prognostic effect of #104 prophylactic dissection by propensity score matching analysis. Between 2012/1 and 2020/12, 302 patients with esophageal malignant tumors underwent radical subtotal esophagectomy via the right thoracic approach at our hospital. The histological types were limited to squamous cell carcinoma, adenocarcinoma, and basal cell carcinoma, and clinical (c)T4b (TNM 7th edition), cM1, cervical esophageal cancer, salvage surgery cases, R1/2 cases, and cases with synchronous advanced multiple cancers were excluded. This resulted in the analysis of the 220 cases comparing between the 3-filed and 2-filed dissection groups. R version 4.1.2 was used for statistical analysis. The predicted probability of #104 dissection was calculated by logistic regression model. Propensity score matching was performed to match patients between 2 groups according to age, tumor location, preoperative treatment, postoperative pneumonia, pathological (p)T factor, and pN factor by nearest neighbor method within caliper. P < 0.05 was considered statistically significant. Results Both DSS and DFS were significantly better in the 2-filed dissection group. Baseline characteristics showed that the 3-filed dissection group had significantly more patients of tumor location Mt and Ut, more squamous cell carcinoma as the histologic type, and more cases with preoperative treatment. In the 3-field dissection group, operative time was significantly longer and the postoperative complications was increased such as recurrent nerve palsy and cervical lymphatic leakage. Pathologic results showed higher grades of pT and pN. Four patients in the 3-field dissection group had p104 metastasis, and only 1 of these survived without recurrence. On the other hand, 5 patients of the 2-field dissection group had #104 as the first recurrence site, and 3 of these had simultaneous distant metastasis. There was no significant difference in DSS and DFS between groups after propensity score matching (DSS p = 0.852, DFS p = 0.768). Conclusions This retrospective study did not confirm a prognostic benefit of prophylactic dissection of the #104 region. This will be elucidated by results of the ongoing RCT, JCOG2013 trial.

Prognostic factors of para-aortic lymph node metastasis from colorectal cancer in highly selected patients undergoing para-aortic lymph node dissection.

We investigated the surgical outcomes of para-aortic lymph node (PALN) dissection in patients with colorectal cancer and assessed the prognostic factors related to the survival. This single-center retrospective study included 31 patients with synchronous or metachronous PALN metastasis from colorectal cancer who underwent PALN dissection between January 2006 and December 2018. Twenty-one patients had synchronous PALN metastasis, and 10 had metachronous PALN metastasis. Seven patients had either simultaneous distant metastasis or a history of distant metastasis other than PALN metastasis at the time of PALN dissection. Eighteen patients underwent adjuvant chemotherapy. The 5-year overall and recurrence-free survival rates were 54.2 and 17.2%, respectively. A multivariable analysis revealed that rectal cancer, metachronous PALN metastasis, and three or more pathological PALN metastases were significantly poor prognostic factors for the recurrence-free survival. Among patients with rectal cancer, lower rectal cancer and lateral pelvic lymph node metastasis were poor prognostic factors for the overall survival. Curative PALN dissection for PALN metastasis from colorectal cancer is feasible with favorable long-term outcomes. A multidisciplinary approach, including surgery and chemotherapy, is needed for colorectal cancer with PALN metastasis to improve the long-term outcomes.

Treatment patterns and results of salvage treatment for regional recurrences after stereotactic ablative radiotherapy for primary non-small cell lung cancer.

Stereotactic ablative radiotherapy (SABR) for early-stage lung cancer has shown promising results; however, regional recurrence (RR) development is not uncommon, and salvage treatment strategies have not been established. We aimed to investigate treatment patterns, prognostic factors, and survival outcomes. A retrospective analysis of 391 patients who underwent SABR for primary lung cancer from 2012 to 2019 was performed. Among these patients, 90 patients showed recurrence, including local recurrence (n=9), RR (n=33), distant metastasis (DM) (n=57), and RR with simultaneous DM (n=8). The median follow-up duration was 17.3 months. The median age was 75 years, and most patients underwent primary SABR due to poor lung function (69.7%). Various salvage treatments were performed in cases of RR, including chemotherapy (n=15), radiotherapy (n=7), concurrent chemoradiotherapy (n=2), and best supportive care (n=9). The median overall survival (OS) and post-recurrence OS (PR-OS) were 22.9 and 11.2 months, respectively. In multivariate analysis, age ≤75 years (HR=0.36, p=0.040), isolated recurrence (HR=0.34, p=0.037), and radiotherapy without chemotherapy (HR=0.25, p=0.024) were significant prognostic factors for PR-OS. Despite various salvage treatments, PR-OS was less than 1 year after RR in our frail patients group who underwent primary SABR. The toxicities of salvage chemotherapy could be quite severe; thus, careful patient selection is required. Further research is needed to validate our findings.

Efficacy of hypofractionated preoperative chemoradiotherapy in rectal cancer.

The efficacy and toxicity of hypofractionated preoperative chemoradiotherapy (HPCRT) combined with oral capecitabine was evaluated in patients with rectal cancer. HPCRT was delivered by intensity-modulated radiotherapy of either 33 Gy to the whole pelvis or 35 Gy in 10 fractions to the primary tumor and 33 Gy to the surrounding pelvis. Surgery was performed 4-8 weeks after HPCRT completion. Oral capecitabine was administered concurrently. A total of 76 patients were eligible for this study, and patient numbers in clinical stages I, II, III and IVA were 5, 29, 36 and 6, respectively. Tumor response, toxicity and survival were analyzed. A total of 9/76 patients (11.8%) achieved a pathological complete response. Sphincter preservation was achieved in 23/32 (71.9%) and 44/44 (100%) of patients with a distal extent from the anal verge of ≤5 and >5 cm, respectively. A total of 28/76 patients (36.8%) achieved tumor-downstaging and 25/76 (32.9%) achieved nodal (N)-downstaging. The 5-year disease-free survival (DFS) and overall survival rates were 76.5% and 90.6%, respectively. In the multivariate analysis for DFS, pathological N stage and lymphovascular space invasion were notable prognostic factors. A total of 6 patients in stage IVA underwent salvage treatments for lung or liver metastasis after HPCRT completion, and all 6 were alive at the last follow-up. Only 4 patients experienced grade 3 postoperative complications. No grade 4 toxicities were observed. HPCRT of 33 or 35 Gy in 10 fractions showed similar results to those of long-course fractionation. This fractionation scheme could be beneficial for patients with early stage disease, locally advanced rectal cancer, simultaneous distant metastasis requiring early intervention or for patients who wish to avoid multiple hospital visits.

Regional lymph node recurrence after stereotactic body radiation therapy for lung cancer: Patterns of recurrence, treatment approaches, and clinical outcomes (KROG 21-09)

PurposeTo present the multi-institutional data on patterns of recurrence, treatment approaches, and clinical outcomes for regional lymph node (LN) recurrence after stereotactic body radiation therapy (SBRT) for primary lung cancer. Materials and MethodsThe medical records of 114 patients who experienced regional LN recurrence as the first recurrence after lung SBRT were retrospectively reviewed. Patterns of recurrence were classified as local recurrence, regional recurrence, and distant metastasis. Clinical outcomes including progression-free survival (PFS) and overall survival (OS) were analyzed. ResultsHalf of the patients had regional LN recurrence only. The most common simultaneous recurrence was distant metastasis (38.6 %). Common sites of regional recurrence were ipsilateral hilar (47.2 %), ipsilateral upper mediastinal (40.6 %), and subcarinal (42.5 %) LN stations. 24 (21.1 %) patients underwent salvage radiation therapy (RT), and 44 (38.6 %) patients underwent palliative treatment. Better OS was observed in the salvage RT group (p = 0.025). The 1-year PFS and OS rates were 27.7 % and 55.2 %, respectively, with salvage RT, 14.0 % and 39.9 %, respectively, with palliative treatment, and 22.8 % and 26.8 %, respectively, with no additional treatment. Multivariate analysis showed that salvage RT (PFS, HR 0.463, p = 0.050; OS, HR 0.312, p = 0.002), palliative treatment (PFS, HR 0.436, p = 0.013; OS, HR 0.553, p = 0.050), and simultaneous distant metastasis (PFS, HR 2.335, p = 0.005; OS, HR 1.726, p = 0.054) affected clinical outcomes. ConclusionMany cases of regional LN recurrence are confined to the locoregional area of patients, and appropriate treatment can improve the prognosis of these patients.

Abstract P3-19-08: Breast cancer related lymphedema in patients undergoing RNI: Is the axillary lateral vessel thoracic junction an organ-at-risk?

Abstract Background: Breast-cancer related lymphedema (BCRL) is a devastating treatment complication driven by the extent of axillary surgery (axillary lymph node dissection [ALND] versus sentinel lymph node biopsy [SLNB]). Regional nodal irradiation (RNI) may increase the risk of BCRL by up to 5%. Recently, investigators identified a region of the axilla known as the axillary-lateral thoracic vessel juncture (ALTJ) as a potential organ-at-risk (OAR) demonstrating that increasing radiation dose to the ALTJ was associated with a higher risk of BCRL. Here, we set to validate whether radiation dose to the ALTJ is associated with BCRL. Materials/Methods: We identified patients with stage II-III breast cancer treated with adjuvant RNI after M or L from 2013-2018 excluding those with BCRL pre-radiation. RNI treatment planning included delineation of clinical target volumes (CTVs): breast or chest wall and regional lymph nodes per the RTOG Breast Cancer Atlas. The CTVs were expanded by 5mm to create the planning target volume (PTV). Dose delivered was 50 Gy/25 fractions with goal of 47.5 Gy (95%) to 95% of each PTV. We defined BCRL as difference in arm circumference between the ipsilateral and contralateral limb >2.5 cm at any 1 visit or ≥2 cm on at least 2 visits. All patients suspected of having BCRL at routine follow-up visits were evaluated by physical therapy. The ALTJ was retrospectively contoured and the following metrics collected: maximum/minimum/mean dose; V10Gy-V50Gy. Follow-up time was defined as the time from surgery to the development of BCRL or last follow-up. Cox proportional hazards regression models were used to test the association between clinical and dosimetric parameters with the development of BCRL. All variables with p<0.10 on univariate analysis were entered in the final multivariate model (p<0.05 considered statistically significant). Results: Population includes 378 patients with median age 53 years (interquartile range [IQR], 45-61 years), median body mass index (BMI) 28.4 kg/m2 (IQR, 24.3-33.4 kg/m2), 60% HR+/HER2-, 89% chemotherapy, 53% stage III, 71% underwent M, and 82% underwent ALND with median of 18 nodes removed (IQR, 11-25) and median of 2+ nodes (IQR, 1-5). Median follow-up time was 54.5 months (IQR, 40.3-72.2 months). The ALTJ and axilla PTV overlapped in 91% of the patients. BCRL developed in 97 patients (25.7%) at a median of 18.9 months (IQR, 9.9-30.6 months). The 4-year cumulative incidence of BCRL was 23.5% (26.6% ALND vs. 8.7% SLNB, p=0.002). On univariate analysis, increasing age (HR=1.02, p=.039), increasing BMI (HR=1.04, p=0.002), increasing number of nodes removed (HR=1.04, p<0.0001), and use of IMRT vs. 3DCRT (HR=1.50, p=0.041) were all significantly associated with developing BCRL while increasing size of the axilla PTV (HR=0.96, p=0.047) was associated with a lower risk. None of the ALTJ metrics were associated with developing BCRL. Increasing ALTJ V45 was marginally associated with a lower risk of BCRL (HR=0.96, p=0.091). On multivariate analysis, increasing age (HR=1.02, p=0.021), increasing BMI (HR=1.04, p=0.004), and increasing number of nodes removed (HR=1.03, p=0.001) were associated with a higher risk of developing BCRL while use of IMRT (HR=1.24, p=0.338), size of the axilla PTV (HR=0.96, p=0.110) and ALTJ V45 (HR=0.99, p=0.708) were not. There were 10 local-regional recurrence (LRR) events as a first failure, 8 of which occurred with simultaneous distant metastases (DM). Of these LRRs, 5 included an axillary nodal component (all with DM) resulting in a 2.6% 4-year LRR rate (1.4% axillary recurrence rate). Conclusion: In this analysis, ALTJ is not validated as a critical OAR for reducing BCRL risk. Until such an OAR is discovered, the axillary PTV should not be modified or dose reduced in efforts to reduce BCRL given the low LRR and inability to validate ALTJ as an OAR. Citation Format: Erin Healy, Sachin Jhawar, Sasha Beyer, Julia R White, Jose G Bazan. Breast cancer related lymphedema in patients undergoing RNI: Is the axillary lateral vessel thoracic junction an organ-at-risk? [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-19-08.

Predictive factors for simultaneous distant metastasis in head and neck cancer patients during the diagnostic work-up.

The incidence of distant metastasis (DM) in patients affected by head and neck squamous cell carcinoma (HNSCC) is relatively low, and multiple risk factors were described for the development of distant metastasis. Retrospective study of patients diagnosed with a HNSCC between July 2016 and July 2020 in a tertiary university hospital. Five-Hundred and sixty-nine patients meet inclusion criteria. In the univariate analysis we found a statistical correlation in those patients affected by a hypopharyngeal tumour (p = < 0.0001), patients older than 60years old (p = 0.01), advanced T stage (p = < 0.0001), a proven positive lymph node (p = 0.02), poorly differentiated tumour (p = < 0.0001), patients with 3 or more positive lymph nodes (p = 0.0001), with ECS (p = 0.0001) and a second primary tumour (p = 0.03). However, according to those results from our multivariable analysis, the factor related to an increased or higher chance to detect a DM during the diagnosis work-up were the presence of a hypopharyngeal primary tumor with a hazard ratio (HR) of 1.14, p = < 0.0001, advanced T stage (T3-T4) with a HR of 1.21, p = 0.001, poorly differentiated tumor with a HR of 1.04, p = < 0.0001, have proven positive lymph node with a HR of 1.03, p = 0.04, have more than three positive lymph node metastases with a HR of 1.25, p = 0.003, the presence of ECS with a HR of 1.40, p = 0.002, and have a second primary tumor with a HR of 1.05, p = 0.01. According to the present study, factors such as hypopharyngeal tumours, advanced T-stage, poor differentiation grade, have more than three positive lymph nodes, ECS and have a second primary tumour should be considered as high-risk indicators for screening. Based on these results, the authors recommend considered an extensive diagnostic work-up in all patients with a high risk of DM development.

Outcome of radiotherapy for clinically overt metastasis to the internal mammary lymph node in patients receiving neoadjuvant chemotherapy and breast cancer surgery

PurposeThis study was aimed to assess the outcome of radiotherapy and determine prognostic factors for survival in breast cancer patients with clinically overt metastasis to the internal mammary lymph node (IMN+). MethodsWe retrospectively reviewed the medical records of 193 patients with IMN + breast cancer who received neoadjuvant chemotherapy (NAC), breast surgery without internal mammary lymph node (IMN) dissection, and postoperative radiotherapy at 9 hospitals between 2009 and 2013. Breast-conserving surgery or mastectomy was performed after taxane-based NAC. Radiotherapy was administered to the whole breast/chest wall and regional nodes. IMN-covering radiotherapy was performed in 92.2% of patients with median dose of 58.4 Gy (range, 44.9–69.1 Gy). The overall survival (OS), disease-free survival (DFS), and IMN failure-free survival (IMNFFS) were analyzed. ResultsAfter median follow-up of 71 months, 9 patients (4.7%) developed IMN failure and simultaneous distant metastasis. The 5-year DFS, OS, and IMNFFS was 68.6%, 81.8%, and 95.3%, respectively. Non-triple-negative breast cancer, Ki-67 ≤ 10%, pathological complete response (CR) in tumor and axillary node, and radiologic CR of IMN after NAC were significant factors for predicting higher DFS; however, IMN radiation dose was not significant determinants for DFS. The 5-year DFS of patients with IMN-dose ≤ 50.0 Gy and those with >50.0 Gy was 86.7% and 76.7%, respectively (p = 0.41). ConclusionsA multimodality strategy including NAC, breast surgery, and IMN-covering radiotherapy was effective for patients with overt IMN + breast cancer. Even without an IMN dissection, most patients were IMN failure-free with an IMN-focusing radiotherapy.

Correlation between CT Texture Analysis and Synchronous Distant Metastasis in Patients with Lymph Node-negative Colorectal Cancer

Objective To investigate the correlation between CT texture analysis and synchronous distant metastasis in patients with lymph node-negative colorectal cancer. Methods The preoperative CT images of 82 patients with lymph node-negative colorectal cancer were analyzed retrospectively.There were 12 patients with simultaneous distant metastasis and 70 patients without simultaneous distant metastasis.The maximum plane of the lesion on plain scan and portal CT images was analyzed by TexRAD software.When the spatial scaling factor(SSF)was 0 and 2-6,six texture parameters were obtained,and the differences of texture parameters between the two groups were compared.The counting data were analyzed by chi-square test and the measurement data by Mann-Whitney test. Results There was a significant difference in the skewness of SSF=3 between the simultaneous distant metastasis group and the non-synchronous metastasis group on plain CT scan(P=0.031).On contrast-enhanced CT images,the entropy values of SSF=2,3,5,and 6 were statistically significant(P=0.048,P=0.027,P=0.016,P=0.017),and the peak values of SSF=2 were statistically significant(P=0.026).According to the comprehensive analysis of the texture parameters of the six groups,when the boundary value was 0.636,the sensitivity and specificity for the diagnosis of simultaneous distant metastasis were 75% and 89%,respectively. Conclusion CT texture analysis is useful in the diagnosis of synchronous distant metastasis in patients with lymph node-negative colorectal cancer.

Locoregional risk assessment after neoadjuvant chemotherapy in patients with primary breast cancer: clinical utility of the CPS + EG score.

Locoregional control is a prerequisite to cure primary breast cancer but the prediction of locoregional recurrence to guide further local therapy following neoadjuvant chemotherapy remains a challenge. The CPS + EG score was designed to predict distant recurrences. Here we examine its ability to predict both not only distant but also locoregional recurrences with respect to accuracy and clinical applicability. Clinical data from 432 patients with primary breast cancer treated with neoadjuvant chemotherapy between 2003 and 2011 were prospectively collected. Using the Kaplan-Meier method we analyzed the risk of local and distant recurrences according to individual CPS + EG scores, stratified by type of surgery. Possible confounding of the relationship between recurrence risk and CPS + EG score by established risk factors was accounted for in multiple survival regression models. Additionally, we analyzed the performance of the CPS + EG score to predict isolated locoregional recurrence by censoring patients with prior or simultaneous distant metastases. 5-year locoregional recurrence-free survival was 90%, and 5-year distant metastases-free survival was 82%. The CPS + EG score stratified patients into six prognostic groups with distinct 5-year locoregional recurrence-free survival, ranging from 100 to 41% (p = 0.02) and 5-year distant metastases-free survival, ranging from 96 to 35% (p < 0.0001). 8 patients (17%) with CPS + EG scores ≥ 4 experienced locoregional recurrence-5 of them presented with simultaneous distant disease. The CPS + EG score, originally designed to predict distant relapse, is also valuable for assessing local recurrence risks. Our data demonstrate that distant and locoregional recurrence risks are closely related. As prognosis of patients with high risk of locoregional failure based on CPS + EG is dominated by distant recurrences, escalating local therapies may have limited impact on overall prognosis.

Abstract P3-12-03: Analysis of radiation dose in the gap region between the supraclavicular target volume to the internal mammary target volume in women receiving regional nodal irradiation

Abstract Purpose: Consensus guidelines for regional nodal irradiation (RNI)/postmastectomy radiation (PMRT) clinical target volumes (CTV) have slight variations amongst leading national organizations. In the US, the Radiation Therapy Oncology Group (RTOG) defines the caudal edge of the supraclavicular (SCV) CTV as the junction of the brachiocephalic and axillary vessels while the internal mammary nodal (IMN) CTV starts at the superior aspect of the medial first rib. This leaves an anatomical gap between the two target volumes. The European Society of Radiation Oncology (ESTRO) does not recommend leaving a gap between the SCV CTV and IMN CTV. We set to analyze radiation dose and patterns of failure in this region. Materials and Methods: We identified consecutive patients treated with RNI/PMRT at our institution from 2013-2016. Patients with metastatic or recurrent disease were excluded. All patients received 50 Gy/25 fractions to the breast/chestwall+regional nodes (including IMN PTV) +/- boost to the lumpectomy cavity/mastectomy scar using 3D conformal radiotherapy (3DCRT) or intensity modulated radiation therapy (IMRT). We retrospectively contoured the vessels from one slice below the caudal border of the SCV PTV contour to one slice cranial to the first IMN PTV contour. We calculated the mean dose and the relative V40Gy, V45Gy, and V47.5Gy of the gap region.A gap failure was defined as a first recurrence in this region with or without simultaneous loco-regional recurrence (LRR) or distant metastases (DM). We used the cumulative incidence method to calculate the gap recurrence rate with DM, LRR, and death, as competing risks. Results: 230 patients were included with median age 52 years, predominantly stage III disease (60%), and most treated with preoperative (51%) or postoperative (41%) systemic therapy. Breast cancer subtype was ER+/HER2- in 138 patients, triple negative in 44 patients, and HER2+ in 48 patients. The median (IQR) mean dose, V40Gy, V45Gy, and V47.5 Gy in the gap region were: 20.3 Gy (14.8-26.2 Gy), 6% (1.3%-20.0%), 0.6% (0%-7.0%), and 0% (0%-1.3%). The mean dose to the gap region was slightly higher in patients treated with IMRT (N=68) compared to 3DCRT (N=162): 25.3 Gy (SD 7.5 Gy) vs. 19.5 Gy (SD 8.0 Gy), p&amp;lt;0.0001. With median follow-up of 32 months, there were 2 recurrences in the gap region, both of which occurred with simultaneous distant metastases. No patients had isolated recurrences in the gap region. The 3-year cumulative incidence of recurrence in the gap region was 0.8%. The predominant pattern of failure was DM (N=31) with a 3-year rate of 14.4% followed by LRR (N=6, 4 with simultaneous distant metastases) with a 3-year rate of 3.1%. Conclusion: In a clinical practice in which we routinely contour and treat the IMN PTV and SCV PTV with a gap region between those two volumes, we found that the mean radiation dose to this region is low, at about 50% or less compared to the prescription dose. Despite this, recurrences in this region are exceedingly uncommon and have not yet occurred in the absence of simultaneous DM. While the follow-up is limited, these data support the current guidelines of not routinely targeting this region. Citation Format: Bazan JG, Dicostanzo D, Healy E, Beyer S, White JR. Analysis of radiation dose in the gap region between the supraclavicular target volume to the internal mammary target volume in women receiving regional nodal irradiation [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-12-03.

Impact of an In Situ Component on Outcome After In-Breast Tumor Recurrence in Patients Treated with Breast-Conserving Therapy.

Among all in-breast tumor recurrences (IBTR) following breast-conserving therapy (BCT), some comprise metachronous new primaries (NPs) while others are true recurrences (TRs). Establishing this distinction remains a challenge. We studied 3932 women who underwent BCT for stage I-III breast cancer from 1998 to 2008. Of these, 115 (2.9%) had an IBTR. Excluding patients with inoperable/unresectable recurrences or simultaneous distant metastases, 81 patients with isolated IBTR comprised the study population. An IBTR was categorized as an NP rather than a TR if it included an in situ component. The log-rank test and Kaplan-Meier method were used to evaluate disease-free survival (DFS) and overall survival (OS), and univariate and multivariate analyses were performed using Cox proportional hazards regression models. At a median of 64.5months from IBTR diagnosis, 28 of 81 patients had DFS events. Five-year DFS was 43.1% in the TR group (p=0.0001) versus 80.3% in the NP group, while 5-year OS was 59.7% in the TR group versus 91.7% among those with NPs (p=0.0011). On univariate analysis, increasing tumor size, high grade, positive margins, lymphovascular invasion, node involvement, lack of axillary surgery, chemotherapy, radiation therapy, and IBTR type (TR vs. NP) were significantly associated with worse DFS. Controlling for tumor size and margin status, TRs remained significantly associated with lower DFS (hazard ratio 3.717, 95% confidence interval 1.607-8.595, p=0.002). The presence of an in situ component is associated with prognosis among patients with IBTR following BCT and may be useful in differentiating TRs and NPs.

Clinical and pathological characteristics and prognostic evaluation of high-risk small renal carcinoma

Objective To study clinical and histopathological features of high-risk small renal carcinoma and provide theoretical basis for the individualized treatment. Methods This retrospective study analyzed the clinical and histological data of 21 patients of high-risk small renal cell carcinomas which were highly aggressive or advanced stage, admitted from Jan 2000 to July 2015. There were 15 males and 6 females, and the average age was (61.5±7.1) years (ranged 27 to 75 years). The mean diameter of tumors was 3.3cm (ranged 2.0 to 4cm). The study mainly focused on pathological character and stage, Fuhrman grading, existence of perirenal tissue or vascular invasion, venous embolus and distant metastasis. Results Of all these 21 cases, 17 cases were clear cell carcinomas, 1 was papillary carcinoma, 2 were hybrid cellular tumor (malignant rhabdoid tumor and sarcomatoid carcinoma) and 1 was sarcomatoid carcinoma. Among the 17 clear cell carcinoma cases, 12 were Fuhrman grade Ⅱ, 5 were grade Ⅲ and one was grade Ⅳ. Tumor infiltrated renal vein or its branches and renal vein embolus were found in 7 cases. The tumor infiltrated perirenal or renal sinus fat were found in 11 cases. Synchronous lung and local lymph nodes metastasis were found in 3 patients respectively. Moreover, there was 1 case with metastasis to the brain (Fuhrman Ⅳ). The final clinical stage were T3aN0M0 in 14, T1aN1M0 in 3 and T1aN0M1 in 4 cases. Conclusions Small renal tumors are heterogeneous in its biological behavior and the minorities are aggressive with infringement of perirenal fat or simultaneous local lymph node or distant metastasis. When the tumor is greater than 3.0 cm in diameter and with high grade in Fuhrman classification, sarcomatoid carcinoma are more likely to be highly aggressive and advanced stage. Key words: Kidney neoplasms; Pathology; Neoplasm metastasis

Recurrent colorectal cancer after endoscopic resection when additional surgery was recommended.

To evaluate the type of recurrence after endoscopic resection in colorectal cancer patients and whether rescue was possible by salvage operation. Among 4972 patients who underwent surgical resection at our institution for primary or recurrent colorectal cancers from January 2005 to February 2015, we experienced eight recurrent colorectal cancers after endoscopic resection when additional surgical resection was recommended. The recurrence patterns were: intramural local recurrence (five cases), regional lymph node recurrence (three cases), and associated with simultaneous distant metastasis (three cases). Among five cases with lymphatic invasion observed histologically in endoscopic resected specimens, four cases recurred with lymph node metastasis or distant metastasis. All cases were treated laparoscopically and curative surgery was achieved in six cases. Among four cases located in the rectum, three cases achieved preservation of the anus. Postoperative complications occurred in two cases (enteritis). For high-risk submucosal invasive colorectal cancers after endoscopic resection, additional surgical resection with lymphadenectomy is recommended, particularly in cases with lymphovascular invasion.

TP53 status predicts long-term survival in locally advanced breast cancer after primary chemotherapy

Background. Before the advent of neoadjuvant chemotherapy, radiotherapy and surgery alone were associated with a high risk of uncontrolled locoregional relapses in locally advanced breast cancer (LABC).Material and methods. In the 1990s we initiated two neoadjuvant protocols, where patients with LABC were given either doxorubicin qW or 5-fluorouracil/mitomycin (FUMI) q3W to shrink the tumours prior to mastectomy and postoperative radiotherapy. Previously, we reported TP53 mutation status to predict a poor response to chemotherapy. Here, we present the long-term survival data, with a follow-up of 20 years in the doxorubicin (n = 90) and 15 years in the FUMI trial (n = 34).Results. Patients in the doxorubicin trial with TP53-mutated tumours experienced a shorter recurrence-free (RFS; 14 vs. 83 months, p < 0.001) and overall survival (OS; 35 vs. 90 months, p < 0.001) than patients with TP53 wt tumours. Similarily, TP53 mutations were associated with a shorter OS (22 vs. 80 months, p = 0.03) and a tendency to shorter RFS (17 vs. 33 months, p = 0.06) in patients treated with FUMI. Furthermore, axillary lymph node metastases predicted shorter OS, but only in patients treated with doxorubicin (49 vs. 142 months, p < 0.04). Applying multivariate analysis, TP53 mutations predicted inferior RFS (p < 0.001) as well as OS (p < 0.001), independently of axillary lymph node status. Isolated local recurrences, without simultaneous distant metastases, occurred in seven patients only in the two trials. Interestingly, chest wall radiation fibrosis predicted improved OS (p = 0.004).Conclusion. TP53 inactivating mutations are associated with an inferior long-term prognosis in patients with LABC treated with conventional chemotherapy.

How Intensive Should Radiotherapy for Head and Neck Cancer With Synchronous Distant Metastases Be? Review of Cases

Given the differences in treatment objectives among oncologists and complexities of standards of therapy for advanced head and neck cancer (HNC), we sought to determine whether HNC patients with simultaneous distant metastases (M1) benefit from aggressive therapeutic intervention. Among the 1,988 patients diagnosed with HNC during a 22-year period, 7 patients with synchronous M1 tumors were identified. Of these individuals, 4 were treated with a prolonged course of radiotherapy for HNC (group A) and 3 were not (group B). The median survival and 60-day mortality rate in group A were 14 months and 0%, respectively, whereas the corresponding observations for group B were 5.5 months and 50%. No difference in HNC stage or M1 extent was present between the 2 groups. The patients composing group A were older than those in group B. These data suggest that some benefit may be obtained by the application of a full course of irradiation for HNC with synchronous M1 disease. The practice of intensive radiotherapy for this particular complicated neoplastic condition needs to be reviewed, considering the health care reform and emphasis on cost-effectiveness in the near future.

Intensity-Modulated Radiotherapy in the Treatment of Oropharyngeal Cancer: Clinical Outcomes and Patterns of Failure

To report outcomes, failures, and toxicities in patients treated with intensity-modulated radiotherapy (IMRT) for squamous cell carcinoma of the oropharynx. Between Aug 2001 and Oct 2007, 107 patients were treated with IMRT with curative intent at Stanford University. Twenty-two patients were treated postoperatively, and 85 were treated definitively. Concurrent platinum-based chemotherapy was administered to 86 patients (80%) and cetuximab to 8 patients (7%). The prescribed dose was 66 Gy at 2.2 Gy/fraction for definitively treated cases and 60 Gy at 2 Gy/fraction for postoperative cases. Median follow-up was 29 months among surviving patients (range, 4-105 months). Eight patients had persistent disease or local-regional failure at a median of 6.5 months (range, 0-9.9 months). Six local failures occurred entirely within the high-risk clinical target volume (CTV) (one with simultaneous distant metastasis). One patient relapsed within the high- and intermediate-risk CTV. One patient had a recurrence at the junction between the IMRT and low-neck fields. Seven patients developed distant metastasis as the first site of failure. The 3-year local-regional control (LRC), freedom from distant metastasis, overall survival, and disease-free survival rates were 92%, 92%, 83%, and 81%, respectively. T stage (T4 vs. T1-T3) was predictive of poorer LRC (p = 0.001), overall survival (p = 0.001), and disease-free survival (p < 0.001) rates. Acute toxicity consisted of 58% grade 3 mucosal and 5% grade 3 skin reactions. Six patients (6%) developed grade >or=3 late complications. IMRT provides excellent LRC for oropharyngeal squamous cell carcinoma. Distant metastases are a major failure pattern. No marginal failures were observed.

Locally recurrent rectal cancer: treatment options

Background. Although the preoperative radiochemotherapy and the optimised surgical technique have improved the outcome in patients with rectal cancer, the local recurrence still remains a therapeutic problem. In up to 50% of patients the local recurrence appears without simultaneous distant metastases. This review highlights current treatment options of locally recurrent rectal cancer. Conclusions. The optimal management of the isolated local recurrence remains a difficult and controversial issue. The radical surgical resection is the mainstay of the curative treatment, but an extended surgery can be associated with significant morbidity and impaired quality of life. The preoperative chemoradiation for turnout down staging increases the chance of resectability and the addition of intraoperative radiotherapy may further improve the local control and survival. Re-irradiation is feasible in patients who already received irradiation as part of the primary rectal cancer treatment.

Breast cancer with synchronous metastases: Impact of locoregional radiotherapy (LRR) on survival

1038 Background: Breast cancer with synchronous metastases is considered as a noncurable disease for which systemic treatment remains the cornerstone of management. However several observational studies have reported a survival benefit for those patients (pts) who were offered a complete excision of the primary tumor. In such setting, locoregional treatment (LRT) may also consist of exclusive locoregional radiotherapy (LRR), as favoured in our institution for the past 2 decades. From our database, we have evaluated the impact of this alternative LRT to surgery on survival of breast cancer pts presenting with synchronous metastases. Methods: Among 18,753 cases diagnosed and treated at Rene Huguenin Cancer Center between 1980 and 2004, 598 pts (3.2%) presented with initial simultaneous distant metastasis. Information regarding demographics, tumor characteristics, site(s) of metastases and treatments were prospectively recorded in the database. The impact of delivery of LRT on overall survival (OS) was evalu...

Phase-II study on stereotactic radiotherapy of locally advanced pancreatic carcinoma

Background and purposeThe majority of patients with pancreatic cancer have advanced disease at the time of diagnosis and are not amenable for surgery. Stereotactic radiotherapy (SRT) may be an alternative treatment for patients with locally advanced disease. The effect of SRT was investigated in the present phase-II trial. Patients and methodsTwenty-two patients with locally advanced and surgically non-resectable, histological proven pancreatic carcinoma were included into the trial. The patients were immobilized by the Elekta stereotactic body frame (SBF) or a custom made body frame. SRT was given on standard LINAC with standard multi-leaf collimator. Central dose was 15Gy×3 within 5–10 days. ResultsEvaluation of response was found to be very difficult due to radiation and tumour related tissue reaction. Only two patients (9%) were found to have a partial response (PR), the remaining had no change (NC) or progression (PD) after treatment. Six patients had local tumour progression, but only one patient had an isolated local failure without simultaneous distant metastasis. Median time to local or distant progression was 4.8 months. Median survival time was 5.7 months and only 5% were alive 1 year after treatment. Acute toxicity reported 14 days after treatment was pronounced. There was a significant deterioration of performance status (P=0.008), more nausea (P=0.001) and more pain (P=0.008) after 14 days compared with base-line. However, 8 of 12 patients (66%) improved in performance status, scored less nausea, pain, or needed less analgesic drugs at 3 months after treatment. Four patients suffered from severe mucositis or ulceration of the stomach or duodenum and one of the patients had a non-fatal ulcer perforation of the stomach. ConclusionsSRT was associated with poor outcome, unacceptable toxicity and questionable palliative effect and cannot be recommended for patients with advanced pancreatic carcinoma.