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Mixed pancreatic epithelial and mesenchymal tumors are rare, usually invasive, entities. Intraductal papillary mucinous neoplasm (IPMN) is a precursor of invasive ductal carcinoma and shares mutations with its invasive counterparts. We report the case of a 72-year-old female with a previously undescribed sarcomatous transformation of a residual IPMN with no evidence of an invasive component. The mesenchymal component showed no heterologous differentiation. Both the epithelial and the mesenchymal populations showed aberrant expression of p53 protein and the same point mutation in KRAS gene. After a 6 month follow up, there were no signs of local or distant relapse. The present case suggests that sarcomatous transformation is possible in non-invasive, intraductal pancreatic lesions.

Introduction Most primary ocular adnexal lymphomas are those involving mucosa‐associated lymphoid tissue (MALT). Radiotherapy (RT) dose regimens in the literature vary from the historically used high doses (up to 56 Gy) to lower dose RT. We aimed to examine our institution’s experience with the use of orbital RT for treating early‐stage primary ocular adnexal MALT lymphoma (POAML). Methods Patients treated for stage I or II POAML over a 12‐year period (July 2006 to June 2018) were identified through institutional databases. Data were retrospectively collated through review of patient records. Descriptive statistical methods were employed to analyse the data. Results Eighteen patients (median age of 67; range 44‐87yrs) with localised POAML (3 cases of bilateral disease) were identified, resulting in a total of 21 evaluable orbits. Eight (44%) patients were female, and all were documented to be of good performance status (ECOG 0‐1). The median follow‐up was 34 months (range 8‐75 months). The commonest dose fractionation used was 20 Gy in 10 fractions (n = 13 orbits) and a 3D conformal or volumetric modulated arc therapy (VMAT) technique was used in the majority of cases. None of the patients experienced an in‐field recurrence. One patient had experienced a contralateral orbital recurrence two years post‐unilateral orbital RT for orbital MALT lymphoma. Three patients experienced distant relapse. Conclusion The use of lower dose orbital RT such as 20 Gy in 10 fractions (or radio biologically equivalent) yields excellent local disease control in the management of ocular adnexal MALT lymphoma. The durability of the response appears to be favourable. Given the indolent nature of the disease and the low levels of toxicity associated with lower dose orbital RT, this regimen remains our favoured approach to the management of localised POAML., We aimed to examine our institution’s experience with the use of orbital RT for treating early‐stage primary ocular adnexal MALT lymphoma (POAML).The use of lower dose orbital RT such as 20 Gy in 10 fractions (or radio biologically equivalent) yields excellent local disease control in the management of ocular adnexal MALT lymphoma.

Background: Giant cell tumor of the bone (GCTB) occurs most often in younger individuals aged between 20 and 40 years. However, it also occurs in a small proportion of elderly people. Therefore, it is necessary to determine the clinical characteristics of GCTB in elderly people, as only few reports have completely examined the characteristics of GCTB in elderly patients. Methods: This retrospective study enrolled 69 patients with benign GCTB. Patients’ information on age, sex, anatomical location and size, Campanacci grade, pathological fracture, treatment for primary tumors, local and distant relapse, and outcome was collected. We compared these clinical courses between the younger and older groups. We divided the age groups into three subgroups: ≤54 years and ≥55 years, ≤59 years and ≥60 years, and ≤64 years and ≥65 years. We compared the two groups in each subgroup. In addition, we examined factors affecting local recurrence and distant metastasis. Results: Tumor size was significantly larger in the older group between the two subgroups of 55 and 60 years. Kaplan-Meier curves for local recurrence-free survival and distant metastasis-free survival between the two subgroups of 65 years showed significant differences (p = 0.0183 and p = 0.0014). In the multivariate logistic regression analyses, female sex, curettage-only surgical procedure, and denosumab usage before surgery affected local recurrence. Conclusion: Age is unlikely to affect local recurrence and distant metastases in GCTB patients, but local recurrence and distant metastases may be noted in elderly patients aged ≥65 years with GCTB.

PURPOSE Rhabdoid tumor of the kidney (RTK) is one of the most aggressive childhood renal tumors. Overall survival ranges from 22% to 47%. The indication for radiation therapy (RT) in usually very young patients is an ongoing discussion. Recent protocols recommend RT independent of local stage, the latter being a good discriminator in other childhood kidney tumors. In this study, we analyze the evidence for RT in regard to risk factors, including tumor stage. METHODS AND MATERIALS This study analyzed 58 patients with RTK from Austria, Switzerland, and Germany treated in the framework of 4 consecutive, prospective renal/rhabdoid tumor studies from 1991 to 2014. All treatment protocols included multimodality treatment, including high-intensity chemotherapy, surgery, and RT. RESULTS Local stage distribution was not applicable, I, II, and III in 1, 6, 11, and 40, respectively. Twenty-nine (50%) patients had stage IV disease at diagnosis. Thirty-seven patients (64%) achieved complete remission, and 49% (18/37) relapsed. Thirty-four patients (60%) patients had progressive disease and died, 17 had local disease, 10 had combined disease, and 7 had distant disease; 2 treatment-related deaths were reported (3%). Twenty-one patients received RT during first-line treatment, 18 of them to all involved sites. Eight of the 34 cases of progressive disease occurred in irradiated patients. The local failure rate of treated patients with local stage II or III disease was 29% (6/18) in patients irradiated to all sites compared with 68% (15/22) in nonirradiated patients. One of 6 stage I patients received RT, and 1 patient experienced distant relapse (2-year progression-free and overall survival both 83% ± 15%). Progression-free survival for local stage II and III disease treated with RT, adjusted for early relapse or treatment abandonment, was 67% ± 11%, compared with 15% ± 7% without RT (P < .0001). CONCLUSION The 68% local failure rate in nonirradiated patients underlines the importance of local treatment. Our experience supports the use of RT for local control in higher stage disease. In contrast, no local relapse in 6 local stage I patients, including 5 nonirradiated patients, suggests omission of RT in this favorable subset of usually infant patients with RTK.

Glioblastoma is a highly infiltrative neoplasm with a high propensity of recurrence. The location of recurrence usually cannot be anticipated and depends on various factors, including the surgical resection margins. Currently, radiation planning utilizes the hyperintense signal from T2-FLAIR MRI and is delivered to a limited area defined by standardized guidelines. To this end, noninvasive early prediction and delineation of recurrence can aid in tailored targeted therapy, which may potentially delay the relapse, consequently improving overall survival. In this work, we hypothesize that radiomics-based phenotypic quantifiers may support the detection of recurrence before it is visualized on multimodal MRI. We employ retrospective longitudinal data from 29 subjects with a varying number of time points (three to 13) that includes glioblastoma recurrence. Voxelwise textural and intensity features are computed from multimodal MRI (T1-contrast enhanced [T1CE], FLAIR, and apparent diffusion coefficient), primarily to gain insights into longitudinal radiomic changes from preoperative MRI to recurrence and subsequently to predict the region of relapse from 143 ± 42 days before recurrence using machine learning. T1CE MRI first-order and gray-level co-occurrence matrix features are crucial in detecting local recurrence, while multimodal gray-level difference matrix and first-order features are highly predictive of the distant relapse, with a voxelwise test accuracy of 80.1% for distant recurrence and 71.4% for local recurrence. In summary, our work exemplifies a step forward in predicting glioblastoma recurrence using radiomics-based phenotypic changes that may potentially serve as MR-based biomarkers for customized therapeutic intervention.

Background: The breast cancer is the most commonly diagnosed cancer in recent years. The use of neoadjuvant chemotherapy (NACT) makes a significant contribution to chemotherapy in breast cancer. We aimed to develop the novel model as a predictor of distant relapse-free survival (DRFS) in breast cancer patients receiving taxane and anthracycline-based NACT.Methods: We collected the mRNA expression datasets of patients from GSE25055 and GSE25065 in Gene Expression Omnibus (GEO). Univariate and Multivariate Cox Regression Analyses were conducted to achieve the prognostic genes that associated with DRFS. Moreover, the E2F target genes were obtained from GSEA. We obtained the intersection genes between the prognostic genes and E2F target genes, then validated in GSE32603 dataset. And we established a nomogram model based on PTTG1 expression level and several clinical characteristics.Results: There were 95 genes confirmed to be associated with DRFS both in GSE25055 and GSE25065. And PTTG1 was validated as a gene related to DRFS and associated with E2F target hallmark using GSEA analysis and chosen as our target gene. The AUC of PTTG1 model was 0.682 indicating a relatively poor prediction performance. Then a novel nomogram was conducted, the receiver operating characteristic (AUC=0.849), C-index (0.805) and calibration plots were applied to assess the effect of this model.Conclusion: Our study found that the E2F target genes, such as the PTTG1 may serve as a potential biomarker in breast cancer, and provided superior estimation of DRFS, which can guide the clinical practice in NACT of breast cancer.

The Authors reported a retrospective study of 100 Leiomyosarcoma (LMS), evaluating factors that may influence Overall Survival (OS), Local Recurrence Free Survival (LRFS), Metastasis Free Survival (MFS). Tumor Size (P = 0,0009), Local Recurrence (P = 0,0487), Distant relapse (P

Lung cancer is a fairly common malignancy. An early diagnosis and a reliable staging and re-staging with the aim to detect both local and distant relapse are of utmost importance in planning the therapeutic management. The imaging diagnostic work-up of patients with lung cancer usually includes conventional imaging (chest X-ray, contrast-enhanced CT, bone scan) and more recently 18F-FDG PET/CT. Great advances in the management of lung cancer are based on the information provided by 18F-FDG PET/CT, as it supplies both metabolic and anatomic information (better localisation). There is vast evidence in the literature demonstrating its utility in (a) characterising benign versus malignant solitary nodules, (b) staging and re-staging lung cancer, (c) guiding the type of therapy, (d) monitoring treatment response and (e) predicting outcome. In particular, given its specificity in differentiating 18F-FDG-avid relapse from post-surgical changes or post-radiation fibrosis (which do not take up 18F-FDG), PET/CT can detect recurrent disease after initial treatment and (being a whole-body technique) has demonstrated high accuracy in the detection of distant metastases or secondary tumours. In conclusion, 18F-FDG PET/CT can be considered a highly accurate and reliable method for staging and re-staging lung cancer, and is highly effective in guiding personalised therapies.

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

Study design Retrospective case series. Purpose To investigate the oncological outcomes, including distant relapse, after en bloc spondylectomy (EBS) for spinal metastases in patients with a minimum of 2-year follow-up. Overview of literature Although EBS has been reported to be locally curative and extend survival in select patients with spinal metastases, detailed reports regarding the control of distant relapse after EBS are lacking. Methods We conducted a retrospective review of 18 consecutive patients (median age at EBS, 62 years; range, 40-77 years) who underwent EBS for spinal metastases between 1991 and 2015. The primary cancer sites included the kidney (n=7), thyroid (n=4), liver (n=3), and other locations (n=4). Survival rates were estimated using the Kaplan-Meier method, and groups were compared using the log-rank method. Results The median operative time and intraoperative blood loss were 767.5 minutes and 2,375 g, respectively. Twelve patients (66.7%) experienced perioperative complications. Five patients (27.8%) experienced local recurrence of the tumor at a median of 12.5 months after EBS, four of which had a positive resection margin status. Thirteen patients (72.2%) experienced distant relapse at a median of 21 months after EBS. The estimated median survival period after distant relapse was 20 months (95% confidence interval, 0.71-39.29 months). No association was found between resection margin status and distant relapse. Overall, the 2-year, 5-year, and 10-year survival rates after EBS were 72.2%, 48.8%, and 27.1%, respectively. Importantly, the era in which EBS was performed did not impact the oncological outcomes. Conclusions Our results suggest that EBS by itself, even if margin-free, cannot prevent further dissemination, which occurred in >70% of patients at a median of 21 months after EBS. These results should be considered and conveyed to patients for clinical decision-making.

The predictive value of Image-Defined Risk Factors (IDRFs) developed by the International Neuroblastoma Risk Group Task Force as it relates to primary-site management is undefined and may aid patient selection for de-escalation of adjuvant radiation therapy to the primary site in high-risk neuroblastoma.Patients (N = 76) with high-risk neuroblastoma treated on prospective trials at our institution from 1997 to 2014 were eligible for inclusion. IDRFs were defined based on pretherapy imaging. Overall survival, progression-free survival, and locoregional failure-free survival (LRFFS) were described using the Kaplan-Meier estimator and tested across strata by using the log-rank test.Twenty of 76 patients (26%) experienced local (n = 6), regional (n = 6), or combined locoregional failure (n = 8) with or without distant failure. Ten (50%) of the locoregional failures had concurrent distant relapse. Of patients who completed all therapy, both those with no IDRFs and those with90% resection had a 3-year LRFFS of 100%, with or without radiation therapy. Patients with either ≥1 IDRF or Gross Total Resection (GTR) or the inability to complete all therapy had inferior 3-year LRFFS of 77.8% and 14.4% with or without radiation therapy, respectively (P .04). Patients treated with a dose ≥30.6 Gy as part of therapy for residual disease had an 83.3% locoregional control rate.Patients with90% tumor resection and no primary site IDRFs at diagnosis may be candidates for de-escalation of adjuvant primary-site radiation therapy, although validation of these findings in future studies is required.

Objective To evaluate the prognostic role of LVSI, evaluated in a semi-quantitative fashion on prognosis of early stage, low risk endometrial cancer (EC). Methods We enrolled patients who underwent surgery for EC between 2003 and 2018 in two referral cancer center. All patients had endometrioid EC, G1-G2, with myometrial invasion Results Among 524 patients, any positive LVSI was found in 57 patients (10.9%) with 6.7% (n=35) focal LVSI and 4.2% (n=22) substantial LVSI. Substantial LVSI was associated to higher rate of G2 (p Conclusions Substantial LVSI represents the strongest independent risk factor for decreased survival and distant relapse, indicating a role for potential hematogenous dissemination.

Although the development of effective combined chemoradiation regimens for esophageal cancers has resulted in statistically significant survival benefits, the majority of patients treated with curative intent develop locoregional and/or distant relapse. Further improvements in disease control and survival will require the development of individualized therapy based on the knowledge of host and tumor genomics and potentially harnessing the host immune system. Although there are a number of gene targets that are amplified and proteins that are overexpressed in esophageal cancers, attempts to target several of these have not proven successful in unselected patients. Herein, we review our current state of knowledge regarding the molecular pathways implicated in esophageal carcinoma, and the available agents for targeting these pathways that may rationally be combined with standard chemoradiation, with the hope that this commentary will guide future efforts of novel combinations of therapy.

Background: Previously we found that SPAG5 gene was amplified/gained in 20-35% of HER2+BC. Herein, we investigated the prognostic and predictive significance of SPAG5 (mRNA, protein) expression in 1726 HER+BC patients with median follow-up >5 years. Methods: Analysis of SPAG5 mRNA (cDNA array expression) and protein (immunohistochemistry) and their association with distant relapse risk (DRR) were determined in 446 and 642 cases of HER+2 early stage BC in which 36% and 40% of them had received adjuvant Herceptin (H) + Anthracycline based (AC) + Taxane (T); respectively. In 33% and 31% of SPAG5 mRNA cohort and 21% and 38% of SPAG5 protein cohort had received adjuvant (Adj) AC+T or chemotherapy (CT) naïve; respectively. The association between SPAG5 expression (mRNA, protein) and both pCR and DRR after receiving neoadjuvant chemotherapy (Neo-Adj-CT) were evaluated in 476 and 162 patients with HER2+ locally advanced BC; respectively. Neo-Adj AC+T+HER2 targeting (Herceptin, Herceptin+ Lapatinib or Lapatinib) and AC+/-T has been prescribed to 51% and 49% of mRNA cohort whereas the 45% and 55% of the protein expression cohort has received Neo-Adj AC+T+H and AC+/-T; respectively. Findings: In patients with SPAG5 mRNA overexpression (+;> median), those who had received AC+/-T Neo-Adj-CT alone achieved similar pCR to those who had received AC+T+HER2 targeting Neo-Adj (38% vs., 37%; OR (95% CI): 1.0 (0.6–1.6), p=0.923) in either ER- (46% vs., 52%; OR (95% CI): 1.3 (0.5–3.0), p=0.58) or ER+ subgroups (25% vs., 26%; OR (95% CI): 1.1 (0.4–3.4), p=0.88). Whereas in patients with low SPAG5 mRNA (-), those who had received AC+T+HER2 targeting Neo-Adj had achieved 2.5 fold increased in pCR compared to those who received AC+/-T alone (47% vs., 26%; OR (95% CI): 2.5 (1.4–4.4), p=0.001) in either ER- (60% vs., 31%; OR (95% CI): 3.4 (1.7–6.7), p Conclusion: SPAG5 expression could help in selecting patients who would benefit from both HER2-targeting agents and or AC-CT. Therefore patients with SPAG5- expression could avoid unnecessary AC-CT whereas those with SPAG5+ could receive a shorter Herceptin course. Citation Format: Abdel-Fatah TM, Ball GR, Ellis IO, Chan A, Chan SY. Sperm associated antigen 5 (SPAG5) predicts pathological complete response (pCR) and distant relapse risk to HER2 targeting agents and anthracycline based chemotherapy in HER2 positive (HER2+) breast cancer (BC) [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 P3-11-08.

Introduction Lymphoedema develops after surgery in 30% patients. In a prospective, multi-centre UK study, we used a validated perometer arm measurement to determine 1) the factors predicting lymphoedema development and 2) the effect of a lymphoedema diagnosis on QoL and survival. Methods Participants (n = 1100) undergoing axillary clearance at 9 centres underwent arm volume measurements pre and post-surgery by perometry, and completed FACT-B+4 and Lymphoedema checklist questionnaires. Relative arm volume increase (RAVI) of >10% diagnosed lymphoedema. Predictors of lymphoedema development were determined using logistic regression, and changes in QoL were assessed using Generalised Estimating Equation (GEE) analyses. Results Median patient age was 56 (range 22 to 90) years; 78% received radiotherapy and 65% chemotherapy. Lymphoedema was detected in 21.4% of women by perometry and 24.4% underwent sleeve application by 24 months. Initial decreases in QoL scores post-surgery were greater in patients with lymphoedema and took longer to return to baseline values (FACT-B p=0.014, TOI p=0.008, ARM subscale p RAVI at 1 month (p25-≤30 and >30, p=0.05), ER status (p=0.05) and number of positive nodes (p Local recurrence was 1.7%. One hundred and twenty-nine patients had died of breast cancer (n=88) or had distant recurrence (n=41) across the study. Lymphoedema (RAVI≥10%) by 9 months was an independent predictor of post 9 months distant disease-free cancer survival (Table). Distant Disease Free Survival (DDFS) after Lymphoedema diagnosis Single variableMultivariableVariable (between 3 and 9 months)nHazard ratio (HR) (95% CI)p-valueHR (95% CI)p-valueRAVI ≥ 10% Yes: 105 vs No9552.30 (1.39-3.81)0.0011.73 (1.01-2.96)0.047ER Status Negative: 1719532.94 (1.92-4.49) Conclusions Lymphoedema is associated with lasting quality of life deficits and early distant relapse. Women at low risk of lymphoedema (75%) can be reassured using the scoring model. Early Arm measurements at 1 month post-surgery a useful measurement time to determine lymphoedema risk and enable patients to be reassured (75%) or plan for lymphoedema monitoring. Citation Format: Bundred NJ, Foden P, Riches K, Morris J, Evans A, Todd C, Bramley M, Skene A, Purushotham A, Keeley V. Prediction model for lymphoedema, and effect of Lymphoedema diagnosis on quality of life (QoL) and distant recurrence from breast cancer [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 P2-07-01.

Surgical resection with wide margins is pivotal for sarcoma treatment but achieving the same for fibular sarcomas is a surgical challenge. Thus, we decided to evaluate our own institutional database of primary fibular sarcomas for surgical treatment, margins and pattern of relapse. From July 2014 to October 2018, we identified fourteen patients with histologically confirmed fibular sarcomas. Limb salvage surgery (LSS) was performed in thirteen patients included in our study. One patient treated with definitive radiotherapy was excluded from final survival and functional analyses. The proximal third fibula was the most common site of involvement (85.7%). Osteosarcoma was the histological diagnosis in eight (57.1%) and Ewing’s in the remaining six (42.9%). All patients with proximal fibular tumours underwent Malawer type II resection. Margins were reported as free in twelve and involved in one case. The mean follow-up period was 37.15 months. In the operated group (n = 13), distant relapse occurred in 3 patients, combined relapse in 1 patient and 10 patients are alive and disease free until the last follow-up. The Kaplan-Meier survival analyses revealed the EFS (event-free survival-local/distant relapse) probability as 72.7% at 24 months and 53% at the end of 42 months. The OS (overall survival) probability at 24 months was 75.5% and 57.5% at the end of 42 months. Although it is difficult to achieve conventional wide margins in fibular sarcomas, our results suggest no increased incidence of local recurrence rates as compared to sarcomas at other common sites as reported in literature. Our series helps in understanding site-specific behaviour of sarcomas while contributing to the available data.

To give the molecular profiling and its association with DFS among women with early breast cancer (EBC) and locally advanced breast cancer (LABC). This cohort study used secondary data from six tertiary cancer hospitals in south India. DFS was calculated from the date of treatment completion to local or distant relapse, death, or last follow-up or date of censoring (31 December 2018) whichever was earlier. Adjusted hazard ratios (HRs) and 95% CIs were calculated using Cox regression analysis. Of 837 women, 288 (34.4%) had EBC and 549 (65.6%) had LABC. The mean age was 52.1 years (SD 10.4). Luminal A was the most frequent molecular subtype (36.7%) followed by triple-negative (25.4%), Her2/neu-enriched (14.9%) and luminal B Her2/neu-positive subtypes (13.1%). Three-year DFS was 92% among EBC and 76% among LABC. Among EBC group, molecular profile was not associated with DFS. On adjusted analysis among LABC group, when compared to luminal A, triple-negative [aHR 3.95 (95% CI 1.78, 7.88)] and Her2-enriched [aHR 2.6 (95% CI 1.21, 5.61)] were associated with relapse. Certain molecular subtypes predicted survival in LABC group. However, early diagnosis and treatment appear to nullify this effect on survival.

Background With most centers reporting excellent disease control following transoral surgery for human papillomavirus (HPV)-related oropharyngeal cancer, data are still lacking regarding management and outcomes in patients who relapse. We describe the treatment outcomes after curative intent therapy for locoregional and distant relapse following transoral surgery for HPV-related oropharyngeal squamous cell carcinoma (OPSCC). Methods A single institution retrospective study in which patients were identified with curatively treated loco-regional or single site distant relapse of HPV-related OPSCC treated initially with transoral surgery (TOS) between 1996 and 2014. Results Among 279 patients, 38 (13.6%) relapsed. 21 (7.5%) had local-regional relapse and 18 were treated with curative intent. Three-year overall survival for loco-regional recurrence with curatively intended treatment was 75.3% (95% confidence intervals 54.3-96.0) with a median follow-up 33 (range: 5-65) months. Among 4 patients with isolated distant metastasis who were treated with curative intent, all subsequently developed second relapse of disease. Conclusion Salvage curative treatment of isolated local-regional relapse after TOS is associated with favorable prognosis and should be offered in appropriate candidates.

Purpose: Chemoradiotherapy (CRT) is the current standard of care for patients diagnosed with locally advanced anal squamous cell carcinoma (ASCC), but some patients develop local and/or distant relapse during follow-up. This study was designed to monitor human papillomavirus (HPV) circulating tumor DNA (ctDNA) levels during CRT in patients with ASCC. Experimental Design: We analyzed samples from patients with HPV16- or HPV18-positive locally advanced ASCC. Blood samples were collected before and after CRT. HPV16 or HPV18 ctDNA detection was performed by droplet digital-PCR. Results: HPV ctDNA was detected before CRT in 29 of 33 patients with stages II–III ASCC [sensitivity: 88%; 95% confidence interval (CI), 72–95]; ctDNA positivity rate was associated with tumor stage (64% and 100% in stages II and III, respectively; P = 0.008). Among ctDNA-positive patients at baseline, ctDNA levels were higher in N+ than in N− tumors (median 85 copies/mL, range = 8–9,333 vs. 32 copies/mL, range = 3–1,350; P = 0.03). ctDNA detection at baseline had no significant prognostic impact. After CRT, three of 18 (17%) patients displayed residual detectable HPV ctDNA; ctDNA detection after CRT was strongly associated with shorter disease-free survival (P < 0.0001). Conclusions: This is the first proof-of-concept study assessing the prognostic value of ctDNA after CRT in locally advanced ASCC. In most patients, HPV ctDNA can be detected before CRT and becomes undetectable during CRT. In this study, we show that residual ctDNA levels after CRT are associated with very poor outcome. Clin Cancer Res; 24(22); 5767–71. ©2018 AACR.

Background The aim of the present study was to evaluate the influence of the applied safety margins of modern intensity-modulated radiotherapy (IMRT) in patients with high-grade meningiomas on local control and recurrence patterns. Methods Twenty patients with a neuropathological diagnosis of a high-grade meningioma (WHO°II or °III) treated with adjuvant or definitive radiotherapy between 2010 and 2015 were included in the present retrospective analysis. All patients were planned PET-based. Recurrence patterns were assessed by means of MRI and/or DOTATATE-PET/computertomography (CT). Results The median follow-up was 31.0 months [95% confidence interval (CI): 20.1–42.0] and the progression-free survival (PFS) after 24 months was 87.5%. Overall, four patients had a local recurrence of their meningioma. Of these, three were located in field according to the prior radiotherapy treatment region, while only one patient had a distant relapse. There were no independent factors influencing progression-free or overall survival (OS). Conclusion After radiotherapy (RT), patients with atypical or anaplastic meningiomas still have a defined risk of tumor recurrence. The aim of the present study was to examine mono-institutional data concerning target volume definition and recurrence patterns after radiotherapy of high-grade meningiomas as there are limited data available. Our data suggest that extended safety margins are necessary to achieve a favorable local control for high-grade meningiomas.

Thyroid carcinoma on struma ovarii (TCSO) is a rare ovarian tumour, derivate from monodermic teratomas. It represents about 0.01% of overall ovarian tumours and 5 to 10% of struma ovarii. The diagnosis is histologic and retrospective after pelvic surgery; radiographic imaging being unspecific. Because of its rarity, the treatment of TCSO is not consensual and should be validated in multidisciplinary team involved in rare ovarian carcinoma. The first treatment is a surgical removal, with a laparoscopic approach. A fertility-conservative surgery is recommended for young women. If the tumour is unresectable and/or with metastatic spread, an adjuvant iodine 131 treatment might be proposed after thyroidectomy. Recurrence of TCSO should be taken care of as a thyroid carcinoma with tyrosine kinase inhibitor in case of progressive distant relapse, refractory to iodine 131 treatment. If the recurrence is localised, a complete surgery is the preferred option. There is no gold standard for the follow up.

Soft tissue sarcoma (STS) mainly occurs in middle-aged and senior citizens. Although a poorer prognosis has been reported for older patients, few studies have examined advanced elderly excessive older patients. We evaluated the clinical features of advanced elderly patients with STS. One hundred and forty-four patients were included in this retrospective study, and we divided them into two groups based on a cut-off age of 85 (older and younger groups). The patients’ information, including age, tumor type, location, size, presence of metastasis, AJCC stage, FNCLCC classification, treatment-related factors, local and distant relapse, and outcome, was collected. We compared the clinical courses between the 2 groups. In all patients, the frequency of chemotherapy in the older group was significantly lower than in the younger group (P

Background: Compared to white women, black women with operable breast cancer treated with primary surgical therapy and adjuvant or neoadjuvant systemic chemotherapy have higher recurrence rates and breast cancer mortality. Large randomized prospective studies did not find significant differences in distant-recurrence free survival (DRFS) and overall survival (OS) between breast cancer patients treated in the adjuvant and neoadjuvant setting for predominantly white populations. However, data indicating that neoadjuvant treatment is equivalent to adjuvant treatment for black breast cancer patients are missing. Here, we first examined racial differences in DRFS among breast cancer patients treated in the neoadjuvant setting at Einstein-Montefiore Center for Cancer Care (EMCCC) in the Bronx, and then investigated if DRFS in black patients treated in the neoadjuvant setting is comparable to DRFS in the adjuvant setting. Methods: We evaluated DRFS in 241 racially diverse patients with localized or regionally advanced breast cancer treated with neoadjuvant chemotherapy between January 2000 and December 2016. In addition, we evaluated DRFS in 474 white and 701 black patients with localized or regionally advanced breast cancer treated with systemic adjuvant (432 whites, 596 blacks) or neoadjuvant (42 whites, 105 blacks) chemotherapy. Using multivariate Cox proportional hazard models, we generated hazard ratios (HR) and 95% confidence intervals (95%CI) for risk of distant recurrence, with adjustment for age (/50 years), stage (I/II vs III), estrogen receptor (ER) status (+ vs -), HER2/neu overexpression (+ vs. -/equivocal/unknown), triple negative (TN) status (yes vs no), and type of systemic chemotherapy (adjuvant vs. neoadjuvant). Results: Black patients treated with neoadjuvant systemic chemotherapy had significantly worse DRFS than white patients (HR=2.29; 95%CI=1.02-5.15, p=0.04). DRFS in non-black Hispanics and patients from racial backgrounds other than Hispanic or black compared to whites was not statistically different. Neoadjuvant chemotherapy was associated with worse DRFS compared to adjuvant chemotherapy in black (HR=3.72; 95%CI=4.03-5.81; p= Conclusion: Black patients with localized breast cancer treated with systemic neoadjuvant chemotherapy not only have inferior DRFS compared to white patients, but also worse DRFS when compared to black patients treated with adjuvant chemotherapy, after adjustment for clinical and pathological covariates. This observation needs to be confirmed in further prospective studies and biologic factors contributing to this finding need to be evaluated. Citation Format: Pastoriza JM, Karagiannis GS, Xue X, Lin J, Condeelis JS, Sparanno JA, Rohan TE, Oktay MH. Black race is associated with worse distant relapse-free survival in breast cancer patients treated with neoadjuvant compared to adjuvant systemic chemotherapy [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 P6-10-02.

Stereotactic body radiation therapy (SBRT) has demonstrated high local control rates in early stage non-small cell lung cancer (NSCLC) patients who are not ideal surgical candidates. However, distant failure after SBRT is still common. For patients at high risk of early distant failure after SBRT treatment, additional systemic therapy may reduce the risk of distant relapse and improve overall survival. Therefore, a strategy that can correctly stratify patients at high risk of failure is needed. The field of radiomics holds great potential in predicting treatment outcomes by using high-throughput extraction of quantitative imaging features. The construction of predictive models in radiomics is typically based on a single objective such as overall accuracy or the area under the curve (AUC). However, because of imbalanced positive and negative events in the training datasets, a single objective may not be ideal to guide model construction. To overcome these limitations, we propose a multi-objective radiomics model that simultaneously considers sensitivity and specificity as objective functions. To design a more accurate and reliable model, an iterative multi-objective immune algorithm (IMIA) was proposed to optimize these objective functions. The multi-objective radiomics model is more sensitive than the single-objective model, while maintaining the same levels of specificity and AUC. The IMIA performs better than the traditional immune-inspired multi-objective algorithm.

Squamous cell carcinoma (SCC) of the rectum is a rare disease with

The goal of curative management of hepatocellular carcinoma is to provide the best chance of remission. However, recurrence rates for both local and distant relapse are high. Patient subgroups at higher risk of these events can be identified based on histological patterns that are closely linked to specific molecular subtypes. Patient outcome has improved with more effective therapeutic strategies thanks to technological advances in surgical techniques and percutaneous ablation. The main goal of controlling the cause of liver disease is to decrease distant/late recurrence and prevent deterioration of hepatic function. Ongoing trials testing the combination of neoadjuvant and/or adjuvant regimens with these procedures as well as routine tumour molecular analysis may modify therapeutic algorithms for hepatocellular carcinoma in the future.

Introduction/Background In many cases surgery of LMS is performed under the indication of presumed leiomyoma (LM) resulting frequently in morcellation. This study analysed it’s influence on prognosis. Methodology Investigations included: Kaplan-Meier analysis, age, tumour size, mitosis index, estrogen receptor and 5-year-overall survival prediction. In order to exclude the impact of primary extrauterine spread on prognosis, only LMS stage pT1ab were analysed. Results From 215 stage pT1ab LMS150 (69.8%) were operated under the indication of LM. In summary, 89 (41.4%) tumors were morcellated. In this group local-relapse-free interval (LFI) was significantly shorter than without morcellation with the highest difference between 2 to 7 years, which becomes irrelevant after 8 years. In contrast, patients with morcellation had a significantly longer distant-metastasis-free interval (MFI). The difference in MFI stayed over the whole-time range without becoming similar to the not morcellated tumours. Considering the latter and the results of the other investigated prognosis factors including the overall survival (OS) probability, the morcellated LMS have had a better prognosis primary. A joint analysis of MFI and LFI (figure 1) showed no differences and the negative effect of morcellation is also after 8 years not relevant. In the same way OS (figure 2) does not change after the morcellation. In conclusion, the primary better prognosis of morcellated LMS becomes identically with the worse prognosis of not morcellated tumours. Additionally, analysis of time from the first locoregional relapse or metastasis to death shows that women with primary local recurrence have a shorter OS. Conclusion Morcellated vs not morcellated LMS show a significant shorter LFI with significantly longer MFI. Combined LFI and MFI like OS are not affected. Due to morcellation the preoperatively better prognosis of morcellated LMS measured by other prognostic factors equals the worse prognosis to tumors without morcellation. Disclosure Nothing to disclose.

Background The prognostic value of tumor-infiltrating lymphocytes (TILs) in curatively resected, but systemically untreated early-stage triple-negative breast cancer (TNBC) was investigated. Materials and methods Patients with systemically untreated early TNBC between 1999 and 2012 were retrospectively reviewed. A low TIL level was defined as the presence of ≤10% stromal TILs Relapses were classified into locoregional and distant relapse. The primary endpoint was breast cancer-specific survival (BCSS). Results In 72 patients, the median TIL value was 10%, and low TIL status was found in 54.2%. Patients with pT1 and nodal-positive disease constituted 75% and 11.1%, respectively. With a median follow-up of 99 months, 26.4% patients experienced relapse; local in 63.2%, distant in 36.8%, and 9.7% died of disease progression. A low TIL level was significantly associated with distant relapse (p=0.013), and inferior 10-year BCSS, which was consistently observed in patients with T1a/b or N0 disease. Conclusion A low TIL level seems to be an intrinsic prognostic factor in systemically untreated patients with early-stage TNBC, even in the T1a/bN0 subset.

The rates and routes of lethal systemic spread in breast cancer are poorly understood owing to a lack of molecularly characterized patient cohorts with long-term, detailed follow-up data. Long-term follow-up is especially important for those with oestrogen-receptor (ER)-positive breast cancers, which can recur up to two decades after initial diagnosis1–6. It is therefore essential to identify patients who have a high risk of late relapse7–9. Here we present a statistical framework that models distinct disease stages (locoregional recurrence, distant recurrence, breast-cancer-related death and death from other causes) and competing risks of mortality from breast cancer, while yielding individual risk-of-recurrence predictions. We apply this model to 3,240 patients with breast cancer, including 1,980 for whom molecular data are available, and delineate spatiotemporal patterns of relapse across different categories of molecular information (namely immunohistochemical subtypes; PAM50 subtypes, which are based on gene-expression patterns10,11; and integrative or IntClust subtypes, which are based on patterns of genomic copy-number alterations and gene expression12,13). We identify four late-recurring integrative subtypes, comprising about one quarter (26%) of tumours that are both positive for ER and negative for human epidermal growth factor receptor 2, each with characteristic tumour-driving alterations in genomic copy number and a high risk of recurrence (mean 47–62%) up to 20 years after diagnosis. We also define a subgroup of triple-negative breast cancers in which cancer rarely recurs after five years, and a separate subgroup in which patients remain at risk. Use of the integrative subtypes improves the prediction of late, distant relapse beyond what is possible with clinical covariates (nodal status, tumour size, tumour grade and immunohistochemical subtype). These findings highlight opportunities for improved patient stratification and biomarker-driven clinical trials. A statistical framework for breast-cancer recurrence uses long-term follow-up data and a knowledge of molecular subcategories to model distinct disease stages and to predict the risk of relapse.

TPS597 Background: Early stage triple negative breast cancer (TNBC) is associated with a high risk of distant relapse. Because TNBC does not currently have specific targeted agents approved for use in the early setting, it is treated primarily with chemotherapy. TNBC may be more immunogenic than other subtypes of breast cancer. Atezolizumab (an anti–PD-L1 antibody), in combination with nab-paclitaxel has been approved in >70 countries for the treatment of PD-L1-positive unresectable locally advanced or metastatic TNBC based on the results of the randomized phase 3 IMpassion130 trial. The phase 3 IMpassion031 study, evaluating atezolizumab in combination with chemotherapy (nab-paclitaxel followed by doxorubicin and cyclophosphamide) in comparison to placebo plus chemotherapy as neoadjuvant treatment demonstrated a statistically significant and clinically meaningful improvement in pCR in both PD-L1 positive and PD-L1 negative tumors. ALEXANDRA/IMpassion030 is a global, prospective, randomized, open-label, phase 3 trial currently investigating the efficacy, safety and pharmacokinetic profile of adjuvant atezolizumab plus standard anthracycline/taxane adjuvant chemotherapy versus chemotherapy alone in early stage TNBC. Methods: ALEXANDRA/IMpassion030 will randomize 2300 patients with operable stage II-III TNBC, confirmed by central pathology review. Patients are stratified by type of surgery, nodal status, and centrally assessed PD-L1 status. Adjuvant chemotherapy consist of weekly paclitaxel 80 mg/m2 for 12 weeks followed by dose dense anthracycline (epirubicin 90 mg/m2 or doxorubicin 60 mg/m2) and cyclophosphamide 600 mg/m2 for 4 doses every 2 weeks or the same chemotherapy regimen (T-EC/AC) given concomitantly with atezolizumab 840 mg every 2 weeks followed by maintenance atezolizumab 1200 mg every 3 weeks until completion of 1 year of atezolizumab. The primary endpoint is invasive disease-free survival (iDFS) and secondary endpoints include, iDFS in the PD-L1 selected tumour status (IC1/2/3) and node-positive subpopulations, overall survival, safety, patient functioning and health related quality of life (HRQoL). Tumor tissue and blood samples will be collected for biomarker research. The first site was activated on May 4 2018, and approximately 373 sites in 30 countries are currently participating in this trial. This trial is sponsored by F. Hoffmann-La Roche Ltd and conducted in partnership with the Breast International Group, Frontier Science and Technology Research Foundation, Institute Jules Bordet and Alliance Foundation Trials. Clinical trial information: NCT03498716.

Background Chemotherapy in eligible patients is increasingly applied in the neoadjuvant setting, as it offers the possibility for 'in vivo' monitoring of the activity to the administered treatment, prevention of early micrometastatic spread and often allows less invasive surgery in patients that would otherwise have needed a mastectomy. The achievement of a pathologic complete response (pCR) after neoadjuvant chemotherapy is a prognosticator for better outcome. However, less is known about the patterns of distant relapse between patients that did and did not achieve pCR. We assessed the differences in sites of first distant relapse after pCR versus non-pCR after neoadjuvant chemotherapy in patients enrolled in the EORTC 10094/BIG-1-00 “p53” trial. Methods The analyzed population consisted of patients enrolled in the “p53” trial that received ≥1 cycle of chemotherapy before surgery and who have been diagnosed with a distant relapse. pCR was defined as no evidence of residual invasive cancer (or very few scattered tumor cells) in the primary tumor and axillary lymph nodes with or without residual ductal carcinoma in situ (DCIS). Intrinsic subtype classification was performed using the 2011 St Gallen consensus. The first site of distant relapse was collected for all patients and was classified as soft tissue, visceral, skeletal or CNS. As primary analysis, the associations between achievement of pCR and sites of distant relapse were investigated in 4 multivariate logistic regression models, one for each site, adjusting for intrinsic subtype and preceding local recurrence (yes/no). Adjusted P-values are reported (Benjamini-Hochberg correction). Secondary analyses include: associations between site of first distant relapse and pCR by subtype, description of concomitant sites of relapse. Results The study included 383 (21%) eligible patients out of the 1856 randomized for the 'p53' trial, of whom 28 (7%) had achieved pCR and 355 (93%) did not. Median follow-up was 5.4 years. Achievement of pCR was associated with a trend towards a decreased presentation with skeletal metastases (21% (pCR) vs 50% (non-pCR), OR=0.32, adj-p=0.071, see Table) and we observed an increase in the proportion of patients with CNS tissue as first site of distant relapse (21% vs 9%, OR=2.39, adj-p=0.183). The trend for skeletal metastases was seen in all subtypes except for Luminal A. Patients with pCR were more likely to present with only one relapse location category when compared to non-pCR (86% vs 69%). Association between site of first distant relapse and pCRSite of first distant relapseNon-pCR N=355pCR N=28Total N=383Median of time from surgery till first distant relapsepCR: Yes vs NoCategoryN(%)N(%)N(%)MonthsOR (95% CI)Adj. p-valueSoft tissue43 (12.1)4 (14.3)47 (12.3)250.94 (0.30, 2.95)0.909Visceral183 (51.5)14 (50.0)197 (51.4)220.80 (0.36, 1.74)0.756Skeletal179 (50.4)6 (21.4)185 (48.3)280.32 (0.12, 0.82)0.071CNS32 (9.0)6 (21.4)38 (9.9)162.39 (0.87, 6.58)0.183 Conclusion In this group of patients treated with neoadjuvant chemotherapy, patients that achieved a pCR were less likely to present with skeletal metastases as first site of distant relapse, even after adjustment for intrinsic subtype. Citation Format: Touati N, Aalders K, Slaets L, Tryfonidis K, Cameron DA, Bonnefoi H. The association between pCR status after neoadjuvant chemotherapy and sites of first distant relapse after surgery: A substudy of the EORTC 10094/BIG-1-00 trial [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-09-13.

Background. Treatment of advanced uterine cervical cancer has advanced little in the last 15 years. Although two phase III trials showed survival benefit with the addition of consolidation chemotherapy (CT) after cisplatin-based chemoradiotherapy (RTCT), it is not considered standard of care. We aimed to evaluate the benefit of consolidation CT compared to no additional treatment in patients treated with RTCT. Methods. This is a retrospective study including 186 patients with FIGO stage IB2, IIA2, or IIB to IVB (paraaortic lymph nodes only) uterine cervical cancer who were treated with standard RTCT alone or RTCT followed by consolidation CT. Overall survival (OS), progression free survival (PFS), and the risk of distant and local relapses were compared between the two treatment groups. Results. At 3 years OS was 91% versus 82.3% (p=0.027), PFS 84.3% versus 54.4% (p=0.047), and distant metastasis free survival (DMFS) 80.4% versus 62.5% (p=0.027) in favor of the consolidation CT group. Multivariate analysis confirmed the benefit of consolidation CT. There was no difference in locoregional free survival (LRFS). Positive lymph node was related to a higher risk of distant relapse. In the lymph node positive subgroup consolidation CT resulted in longer OS (p=0.050), PFS (p=0.014), and DMFS (p=0.022); in the lymph node negative subgroup there was no benefit from consolidation CT. Conclusions. Use of consolidation CT resulted in longer OS and PFS, mostly due to control of distant relapses. Patients at higher risk of distant relapse showed the greatest benefit. This data generates a hypothesis that could help to better select patients to consolidation CT.

Purpose: Cancers with short interval between diagnosis and metastasis are associated with aggressive clinical course. Specifically, metastatic relapse of triple-negative breast cancer (TNBC) within 2 years of initial primary diagnosis is associated with marked chemoresistance, rapid progression, and poor prognosis. We hypothesized that rapid relapse TNBCs (rrTNBC; distant metastatic relapse or death 2 years) or no relapse (nrTNBC; no distant relapse or death with at least 5 years follow-up). Patients and Methods: We identified 453 primary TNBCs from three publicly-available datasets and characterized each as rrTNBC, lrTNBC, or nrTNBC. We compiled primary tumor clinical and multi-omic data, including transcriptome (n=453), copy number alterations (CNAs; n=317), and mutations in 171 cancer-related genes (n=317), then calculated expression and immune signatures. Results: Patients with rrTNBC were higher stage at diagnosis (Chi-square p Citation Format: Yiqing Zhang, William Nock, Meghan Wyse, Zachary Weber, Elizabeth J Adams, Asad Sarah, Sinclair Stockard, David Tallman, Jasneet Singh, Junu Bae, Eric P Winer, Nancy U Lin, Yi-Zhou Jiang, Ding Ma, Peng Wang, Leming Shi, Wei Huang, Zhi-Ming Shao, Claire Verschraegen, Mathew Cherian, Maryam B Lustberg, Bhuvana Ramaswamy, Sagar Sardesai, Jeffrey VanDeusen, Nicole Williams, Wesolowski Robert, Daniel G Stover. Machine learning predicts rapid relapse in triple negative breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-05-02.

ObjectiveThe identification of patients with endometrial cancer (EC) at higher risk for relapse is critical to individualize and better tailor postoperative treatment. No evidence is available regarding the possible association between tumor size (TS) and the risk of local recurrence. The purpose of this study was to analyze the correlation between TS and risk/type of recurrence in EC patients, stratified according to the new European Society of Medical Oncology-European Society of Gynecological Oncology-European Society for Radiotherapy and Oncology classification.MethodsData of patients with histologically proven EC who received primary surgical treatment between November 1999 and June 2015 were retrospectively retrieved from 5 institutions. Optimal TS cutoff was calculated using a receiver operating characteristic curve. Site of recurrence as a function of TS and groups of risk were analyzed. Local recurrence-free survival, recurrence-free survival, and overall survival were calculated using the Kaplan-Meier method.ResultsData of 1166 patients were analyzed. Among them, 514 (44.1%) had low-risk EC, 174 (14.9%) had intermediate risk EC, 173 (14.8%) had high–intermediate risk EC, and 305 (26.2%) had high-risk EC. A total of 134 (11.5%) women had recurrence: 47 (4%) of them had local relapse, 30 (2.6%) had locoregional relapse, and 57 (4.9%) had distant relapse. Tumor size 25 mm or greater emerged as the threshold for the prediction of a higher rate of local recurrence (P < 0.0001, hazard ratio = 18.2, P = 0.005) and a lower local recurrence-free survival and recurrence-free survival (P < 0.0001) only in patients with low-risk EC. There was no statistically significant correlation between TS and recurrence in the other risk groups.ConclusionsIn this very large series, tumor size emerges as an independent prognostic factor of local recurrence in women with low-risk EC and could be a valuable additional criterion to personalize the treatment approach to these patients.

Purpose We investigated the relationships between metastasis-free interval (MFI) and tumor characteristics, and assessed the prognostic value of MFI for survival after metastasis in patients with metastatic breast cancer. Furthermore, we compared MFI among the subtypes. Methods We identified 335 patients with postoperative tumor recurrence at distant site(s). All patients underwent curative resection and had a MFI of at least 6 months. MFI was categorized as short (

Objective. To evaluate the diagnostic impact of 11C–Choline PET / CT in the detection of recurrent prostate cancer (PCa) in patients with biochemical relapse after radical prostatectomy and to assess the correlation between PSA levels and PET / CT detection rate of PCa relapse.Subjects and methods. 85 patients with biochemical relapse (mean PSA 3.51 ± 3.87 ng / ml) after radical prostatectomy (n = 64) and radiotherapy (n = 21) underwent 11C–Choline PET / CT. According to PSA level, patients were divided into three groups:  2 ng / ml, 2 to 9 ng / ml and > 9 ng / ml.Results. Overall, 11C–Choline PET / CT detected PCa relapse in 33 of 85 patients (39 %). The mean PSA value in PET-positive patients was 5.78 ± 4.95 (0.22–17.80) ng / ml, while in PET-negative patients – 1.43 ± 1.08 (0.28–4.57) ng / ml. Positive PET / CT results were obtained in 9 of 40 patients (22 %) with PSA of < 2 ng / ml, in 17 of 38 patients (45 %) with PSA of 2 to 9 ng / ml, and in 7 of 7 patients (100 %) with PSA of > 9 ng / ml. Local relapse was detected in 42 % (14 / 33) patients. Both local and distant metastases were diagnosed in 39 % (13 / 33) cases. Distant relapsewas identified in 19 % (6 / 33) cases. PET / CT allowed to assess the efficacy of treatment in 26 % (12 / 47) PET-negative patients under hormone therapy at the scan time. However, PET / CT wasn’t able to localize the site of PCa recurrence in these hormone-ensitive patients what might have affected the overall detection rate.Conclusion. 1) 11C–Choline PET / CT was able to detect and correctly identify the site of PCa relapse in 39 % cases and therefore was useful in determining the further therapeutic approach. 2) Our data confirmed the strong correlation between PSA levels and 11C–Choline PET / CT detection rate of PCa relapse (r = 0.9; p < 0.001). 3) 11C–Choline PET / CT has limited utility in localizing the site of PCa recurrence in some patients under hormone therapy.

Advancements in rectal cancer treatment have resulted in improvement only in locoregional control and have failed to address distant relapse, which is the predominant mode of treatment failure in rectal cancer. As the efficacy of conventional chemoradiotherapy (CRT) followed by total mesorectal excision (TME) reaches a plateau, the need for alternative strategies in locally advanced rectal cancer (LARC) has grown in relevance. Several novel strategies have been conceptualized to address this issue, including: 1) neoadjuvant induction and consolidation chemotherapy before CRT; 2) neoadjuvant chemotherapy alone to avoid the sequelae of radiation; and 3) nonoperative management for patients who achieved pathological or clinical complete response after CRT. This article explores the issues, recent advances and paradigm shifts in the management of LARC and emphasizes the need for a personalized treatment plan for each patient based on tumor stage, location, gene expression and quality of life.

In patients with locally advanced, resectable rectal adenocarcinoma, preoperative long course chemoradiation or short-course radiation are currently considered the standards of care. Neoadjuvant radiotherapy, along with improvements in surgical techniques and imaging have dramatically reduced the risk of local recurrence. Disappointingly, these advances have not translated into reduction of risk of distant relapse or improvement in overall survival for these patients. Furthermore, pelvic radiation may be associated with several toxicities, both short and long-term. Recent data suggest that not all patients may need neoadjuvant radiotherapy, and that advances in systemic chemotherapy could be leveraged in the neoadjuvant setting to improve risk of both local and distant relapse. Based on these emerging data, several, ongoing, randomized trials are evaluating neoadjuvant approaches limiting the role of radiotherapy. In this chapter, we summarize the current state of knowledge and ongoing trials in this area. We propose that until the results of these trials are available, neoadjuvant chemotherapy without radiation should be considered investigational or only limited to those with clear contraindications to pelvic radiation. We believe these trials will likely show that preoperative chemoradiation may be more appropriate for certain groups of patients, while preoperative chemotherapy may be appropriate for other groups of patients.