High Risk Of Locoregional Relapse Research Articles

Radiotherapy resistance: identifying universal biomarkers for various human cancers.

Radiotherapy (RT) is considered as a standard in the treatment of most solid cancers, including glioblastoma, lung, breast, rectal, prostate, colorectal, cervical, esophageal, and head and neck cancers. The main challenge in RT is tumor cell radioresistance associated with a high risk of locoregional relapse and distant metastasis. Despite significant progress in understanding mechanisms of radioresistance, its prediction and overcoming remain unresolved. This review presents the state-of-the-art for the potential universal biomarkers correlated to the radioresistance and poor outcome in different cancers. We describe radioresistance biomarkers functionally attributed to DNA repair, signal transduction, hypoxia, and angiogenesis. We also focus on high throughput genetic and proteomic studies, which revealed a set of molecular biomarkers related to radioresistance. In conclusion, we discuss biomarkers which are overlapped in most several cancers.

Safety And Efficacy Of Short-Course Preoperative Stereotactic Body Radiation Therapy For Resectable Pancreatic Cancer: A Prospective Clinical Trial

Resected adenocarcinoma of the pancreatic head has a high risk of locoregional relapse. Adjuvant chemotherapy has become standard of care while the benefit of radiotherapy is still debated. In a prospective clinical trial, we investigated the safety and efficacy of preoperative SBRT in patients with resectable adenocarcinoma of the pancreatic head. A single institution IRB approved pilot study was conducted. Eligible patients had a histologic diagnosis of pancreatic head adenocarcinoma. Patients were determined to be resectable following consultation with hepatobiliary surgery and based on NCCN guidelines. Patients underwent CT simulation with stereotactic s-ray body markers and gold fiducial placement as clinically warranted. A dose of 25 Gy in 5 fractions was prescribed to the PTV which included the gross tumor plus margin of 3-5mm. Patients underwent pancreaticoduodenectomy 1-3 weeks following completion of SBRT. Adjuvant treatment was delivered per medical oncology. Our primary objective was to evaluate the feasibility of preop SBRT and assess the rate of acute radiation toxicity and impact on surgical complication rate. Data from trial patients were compared with institutional historical controls who underwent pancreaticoduodenectomy alone during the same time frame. Wilcoxon Rank Sum test was used for continuous data and Fisher exact test for categorical data. Eighteen patients were enrolled between March 2015 and May 2018. Thirteen patients completed SBRT and underwent surgery. Three patients underwent SBRT but did not undergo pancreaticoduodenectomy due to locally extensive or metastatic disease found at surgery. One patient underwent SBRT then was found on imaging to have suspicious lung lesions and did not undergo surgery. One patient was enrolled but did not receive SBRT due to lung lesions found on screening imaging. SBRT was well tolerated with only 1 case of grade 2 toxicity. For resected patients, a median of 7 days elapsed between end of SBRT and surgery (range 3-20). Surgery was not delayed in any patient due to SBRT. See table 1 for surgical details. Five of ten patients analyzed had significant treatment response (TRG Grade 2) noted on pathology. Preoperative SBRT for resectable pancreatic cancer appears to be feasible and safe. While there was an increased rate of fibrosis noted during surgery, this did not appear to lengthen operating time, hospital stay or result in more complications. Additional follow up is needed for evaluating oncologic outcomes.Abstract 1191; Table 1Preop SBRT N=13Surgery Only N=21p valueMedian Operating Time330 min356 min0.86Median Blood Loss200 cc200 cc0.40Median Hospital Stay6100.08Increased Fibrosis8 of 13 patients2 of 21 patients0.002Major Complications1 of 13 patients2 of 21 patients1.00R0 Resection8 of 13 patients16 of 21 patients0.45 Open table in a new tab

Tongue carcinoma in young adults: a review of the literature.

A recent reduction in the number of smoke-related tumours has been observed thanks to the diffusion of anti-tobacco campaigns carried out in the majority of developed countries. Nevertheless, as demonstrated by recent global epidemiologic studies, squamous cell carcinoma of the mobile tongue appears to be progressively increasing in incidence, particularly among young adults and especially in females. The driving mechanism responsible for such changes is still to be precisely defined. Several genetic studies have compared the mutational pattern of tongue squamous cell carcinoma in young adults to that of more elderly patients, without identifying significant differences that may help in better characterising this subgroup of subjects. Tongue squamous cell carcinomas in young adults have been historically considered as particularly aggressive clinical entities, with a high risk of loco-regional relapse, survival rates inferior to those of the general head and neck cancer group and need for a more aggressive therapy. However, considering the most recent studies, prognostic results in this patient group are heterogeneous and it is not possible to confirm this tendency. Thus, it is not justified to embrace different therapeutic approaches according to patient age. Eventually, an additional element to consider when examining young subjects affected by tongue cancer is the possibility of genetic predisposition. Alterations affecting pathways involved in DNA repair, surveillance of genetic stability or regulation of cellular growth may determine an increased likelihood of developing head and neck cancers.

Radiothérapie postopératoire des carcinomes médullaires de la thyroïde à haut risque de rechute locorégionale

PurposeTo assess the outcome of locally advanced medullary thyroid carcinoma treated with surgery and adjuvant external beam radiotherapy. Patients and methodsTwenty-nine consecutive patients with non-metastatic medullary thyroid carcinoma treated in our institution between January 1995 and December 2012 were retrospectively evaluated. All underwent curative-intended optimal surgery, followed by external beam radiotherapy because of high risk of locoregional relapse. Twelve patients were stage III, 16 IVa and 1 IVb. Positive surgical margins were present in 11 cases (10 R1 and 1 R2). Median and average preradiotherapy serum calcitonin were 141pg/mL and 699pg/mL, respectively. Fourteen patients received 3D-conformal radiotherapy and 15 received intensity-modulated radiotherapy. Median prescribed dose was 63Gy to the high-risk volumes and 54Gy to the low-risk volumes. Treatment was delivered in 30 fractions. The median gap between surgery and radiotherapy was 1.9months. Median follow-up was 76.4months. ResultsKaplan-Meier estimates of 5-year locoregional relapse-free survival and overall survival were 79 and 96 %, respectively. Among the five locoregional relapses, two were related to a macroscopic metastatic cervical lymph node that was unfortunately not removed during the lymphadenectomy. Eight of ten patients with microscopic positive margins (R1) were controlled regarding the thyroidectomy bed. Eight patients had normal serum calcitonin after external beam radiotherapy, of whom only one developed a locoregional relapse during follow-up. Regarding the 21 patients with persistent positive serum calcitonin after treatment, only ten developed a macroscopic locoregional or distant relapse. One grade III and no grade IV acute morbidity were reported. Fifteen patients reported grade II chronic morbidity and no grade III/IV. ConclusionMaximal surgery followed by adjuvant external beam radiotherapy as a treatment for locally advanced medullary thyroid carcinoma provides a high rate of long-term locoregional control and overall survival with limited toxicity. Postoperative external beam radiotherapy should be considered when patients present features indicating a high risk of locoregional relapse.

Risk factors for locoregional relapse after transoral robotic surgery for human papillomavirus-related oropharyngeal squamous cell carcinoma.

Factors predicting locoregional relapse after surgery for oropharyngeal squamous cell carcinoma (SCC) were identified in the pre-human papillomavirus (HPV) era. We examined whether traditional indications for adjuvant radiotherapy (RT) or adjuvant chemoradiotherapy (CRT) still correlate with locoregional relapse in HPV-positive patients after transoral robotic surgery (TORS). Retrospective review of oropharyngeal SCC cases identified patients with HPV-positive tumors who did not receive adjuvant therapy after TORS despite intermediate or high-risk features. Median follow-up was 26.7 months (range, 4.9-73.1 months). Five of 25 eligible patients (20%) relapsed at a median 4.8 months (range, 3.2-7.8 months). Two of 18 (11%) intermediate and 3 of 7 (43%) high-risk patients relapsed. Kaplan-Meier 2-year locoregional relapse-free survival estimates for intermediate and high-risk patients were 88% and 57% (p = .078), respectively. Traditional indications for adjuvant RT or CRT were associated with high risk of locoregional relapse in HPV-positive patients treated with TORS alone. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1674-E1679, 2016.

The role of perioperative radiotherapy in gastric cancer.

Gastric cancer is one of the most common neoplasms and a main cause of cancer-related mortality worldwide. Surgery remains the mainstay for cure and is considered for all patients with potentially curable disease. However, despite the fact that surgery alone usually leads to favorable outcomes in early stage disease, late diagnosis usually means a poor prognosis. In these settings, multimodal therapy has become the established treatment for locally advanced tumors, while the high risk of locoregional relapse has favored the inclusion of radiotherapy in the comprehensive therapeutic strategy. We provide a critical, non-systematic review of gastric cancer and discuss the role of perioperative radiation therapy in its treatment.

The role of perioperative radiotherapy in gastric cancer

Gastric cancer is one of the most common neoplasms and a main cause of cancer-related mortality worldwide. Surgery remains the mainstay for cure and is considered for all patients with potentially curable disease. However, despite the fact that surgery alone usually leads to favorable outcomes in early stage disease, late diagnosis usually means a poor prognosis. In these settings, multimodal therapy has become the established treatment for locally advanced tumors, while the high risk of locoregional relapse has favored the inclusion of radiotherapy in the comprehensive therapeutic strategy. We provide a critical, non-systematic review of gastric cancer and discuss the role of perioperative radiation therapy in its treatment.

Outcomes in Patients Treated With Mastectomy for Ductal Carcinoma In Situ

To examine, in a large, population-based cohort of women, the risk factors for recurrence after mastectomy for pure ductal carcinoma in situ (DCIS) and to identify which patients may benefit from postmastectomy radiation therapy. Data were analyzed for 637 subjects with pure DCIS, diagnosed between January 1990 and December 1999, treated initially with mastectomy. Locoregional relapse (LRR), breast cancer-specific survival, and overall survival were described using the Kaplan-Meier method. Reported risk factors for LRR (age, margins, size, Van Nuys Prognostic Index, grade, necrosis, and histologic subtype) were analyzed by univariate (log-rank) and multivariate (Cox modeling) methods. Median follow-up was 12.0 years. Characteristics of the cohort were median age 55 years, 8.6% aged ≤ 40 years, 30.5% tumors >4 cm, 42.5% grade 3 histology, 37.7% multifocal disease, and 4.9% positive margins. At 10 years, LRR was 1.0%, breast cancer-specific survival was 98.0%, and overall survival was 90.3%. All recurrences (n=12) involved ipsilateral chest wall disease, with the majority being invasive disease (11 of 12). None of the 12 patients with recurrence died of breast cancer; all were successfully salvaged (median follow-up of 4.4 years). Ten-year LRR was higher with age ≤ 40 years (7.5% vs 1.5%; P=.003). Mastectomy provides excellent locoregional control for DCIS. Routine use of postmastectomy radiation therapy is not justified. Young age (≤40 years) predicts slightly higher LRR, but possibly owing to the small number of cases with multiple risk factors for relapse, a subgroup with a high risk of LRR (ie, approximately 15%) was not identified.

P3-14-20: Concomitant Taxane-Anthracyclin Regimen for Neoadjuvant Chemotherapy of Primary Breast Cancer: Experience from a Cohort of 223 Patients Treated in a Single Institution.

Abstract Background: Neoadjuvant chemotherapy (NAC) may be an alternative to mastectomy for localized breast cancer ineligible for breast conservation. The optimal schedule (sequential versus concomitant) remains controversial. Based on encouraging results of a phase 2 study (Luporsi E. et al, ASCO 2000) a concomitant docetaxel (D) and epirubicin (E) neoadjuvant combination is applied in neoadjuvant setting in our institution since 2001 for HER2−negative patients (pts). The results of this combination are presented, with a particular focus on pathological complete response (pCR) and conservation rate. Methods: Between 2001 and 2010, 223 pts received NAC for a T2-T3 breast cancer initially ineligible for conservative surgery, but with hope of breast conservation in case of downstaging by pre-operative medical treatment. Six cycles of D (75mg/m2) and E (75mg/m2) were administered every 3 weeks before surgery, with prophylactic support of G-CSF in order to reduce the risk of febrile neutropenia and to maintain the dose-intensity of the NAC. All patients eligible for breast conservation after NAC underwent lumpectomy, the others were treated by mastectomy. In all cases, an axillary dissection was performed. After lumpectomy all patients received radiation therapy, after mastectomy RT was limited to high risk of loco-regional relapse. Patients with positive hormonal receptors (HR+) received hormonal therapy. Results were analyzed in term of breast conservation rate (BCR), pathologic response rate (pCR defined as no residual invasive tumour in breast and axilla, according to Sataloff's classification) and safety. Results: Mean age of patients was 49,6 years (range: 26–71). Median clinical tumor size was 40mm (range 20–110). Histological subtypes were:78,0 % ductal, 15,3 lobular, 1,8 % ductal/lobular and 4,9 % other types. SBR grading was: grade I: 14,3 %, grade II: 46,2 %, grade III: 33,2 % and 6,3 % unspecified. 77,3 % were HR+, 19,7 % of tumours were triple negative (HER2 unknown for 38 cases). A breast conservation was achievable for 73,5% of patients, the pCR rate was 20,6%. At a median follow up of 48 months, 31 pts relapsed: 9 pts (4%) experienced a local relapse, 5 regional and 28 distant recurrences occured. Additional data about safety and survival will be provided for the meeting. Conclusions: For HER2−negative tumours, 6 cycles of a concomitant taxane-anthracyclin pre-operative combination allowed a 20,6% pCR rate, slightly lower than obtained with 8 cycles of a sequential regimen in several published trials. However breast conservation rate was similar with a low risk of local recurrence. According to these results, concomitant cytotoxic combination is an acceptable option for neoadjuvant treatment of breast cancer. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-14-20.

Prognostic value of tissue polypeptide antigen in oral squamous cell carcinoma

Human oral cancer has a high risk of locoregional relapse which is difficult to diagnose early due to lack of prognostic markers. We and others have shown aberrant expression of cytokeratin (CK) 8 and 18 in human oral cancer. Aberrant supra-basal expression of CK19 has been shown earlier. In this study, our aim was to develop a non-invasive test for prognostication of human oral cancer. Immunoradiometric assay (IRMA) was used to measure the circulating levels of TPA in the sera of 80 oral cancer patients before surgery and seven days after surgery. Elevated serum TPA levels were noted in the post surgery samples of 28 out of the 50 patients for whom clinical follow-up was available, as compared to their pre-surgery samples. TPA levels in the pre-surgery serum samples of patients were significantly higher than levels in the sera of healthy controls (p=0.001). Elevated levels in patients correlated significantly with stage (p=0.02), development of recurrence (p<0.006), and impacted survival (p<0.033). IHC analysis showed statistically significant correlation between expression of CK8, 18 and 19 in surrounding uninvolved tissues of the tumour and post surgery elevated serum TPA levels (p<0.001). This suggests the possibility that CK fragments are released from the surrounding uninvolved tissues into the sera of patients after surgical removal of the tumour. Thus, our study indicates that TPA can be a useful tumour marker for the prediction of recurrence and poor prognosis in human oral cancer.

Postoperative radiotherapy following mastectomy for high-risk breast cancer: a randomised trial

Grade III, node-positive breast cancer carries a high risk of loco-regional relapse after simple mastectomy. A randomised trial was conducted to assess whether this would be significantly reduced by postoperative radiotherapy. Between 1985 and 1991, 76 patients who had undergone a simple mastectomy and axillary sampling, and whose tumours had been found to be grade III and node-positive, were randomised to receive postoperative radiotherapy to the chest wall and axilla or no further loco-regional treatment. Radiotherapy was delivered with 8 MV X-rays to the axilla and supraclavicular fossa and with 8 MeV electrons to the chest wall, to a dose of 45 Gy in 15 fractions over 3 weeks. All patients have been followed-up until death, or for a minimum of 10 years. All loco-regional recurrences occurred within the first 4 years after mastectomy. There were 26 such events in the 40 patients randomised to the ‘watch’ policy (65%), as opposed to 9 out of 36 (25%) who received radiotherapy (P<0.01). Ten-year survival was 39% in the radiotherapy arm as opposed to 25% in the no radiotherapy arm. Recruitment to the trial was closed in 1991, when a preliminary safety analysis revealed the size of the effect of radiotherapy, and from then on all node-positive patients with grade III tumours have routinely been given this treatment. Further follow-up has confirmed this finding, as borne out by these 10-year results, which shows that radiotherapy has a significant impact on reducing loco-regional recurrence in patients at high risk after mastectomy. There is an apparent survival benefit although, because of the small numbers in this trial, this has not reached statistical significance.