PD-1 Blockade With Concurrent Radiotherapy for Locally Advanced Inoperable Cutaneous Squamous Cell Carcinoma.

INTRODUCTION: For patients with locally advanced cutaneous squamous cell carcinoma (LA-cSCC), radiotherapy alone (RT) is often the only treatment option with modest tumor response. We report the outcomes of using combination of programmed cell death protein-1 (PD-1) inhibitor and RT in the treatment of inoperable LA-cSCC. The study presents the efficacy and safety data for the patients with LA-cSCC treated with this combination. METHODS: During the period 2018-2020, a total of 7 patients with biopsy proven inoperable LA-cSCC were treated with combination of PD-1 inhibitor cemiplimab and concurrent RT (Cem-RT). The patients were followed up for safety and efficacy of the Cem-RT regimen and the primary endpoints were objective tumor response and toxicity. RESULTS: The median age of patients was 68 years (range, 64-94). All patients had ECOG performance score 0-1. Six patients initially received cemiplimab and concurrent RT was added to PD-1 inhibitor when there was an inadequate therapeutic response. One patient received concurrent Cem-RT. RT with PD-1 antibody was well tolerated. Six patients developed grade ≤2 dermatitis and 1 patient (patient no. 3) developed acute grade 3 skin reaction. During the post-RT follow up, 3 patients discontinued cemiplimab due to significant toxicities. At the time of reporting , 5 patients remain in complete remission. One patient developed lung metastasis and is currently receiving best supportive care. CONCLUSIONS: The Cem-RT combination was safe and well tolerated with significant tumor response suggesting Cem-RT may be a viable therapeutic option for LA-cSCC. Our hypothesis generating data support the rationale for future prospective studies.

Interventions for preventing osteoradionecrosis of the jaws in adults receiving head and neck radiotherapy.

BACKGROUND: Osteoradionecrosis (ORN) of the jaws is among the most serious oral complications of head and neck cancer radiotherapy, arising from radiation-induced fibro-atrophic tissue injury, manifested by necrosis of osseous tissues and failure to heal, often secondary to operative interventions in the oral cavity. It is associated with considerable morbidity and has important quality of life ramifications. Since ORN is very difficult to treat effectively, preventive measures to limit the onset of this disease are needed; however, the effects of various preventive interventions has not been adequately quantified. OBJECTIVES: To assess the effects of interventions for preventing ORN of the jaws in adult patients with head and neck cancer undergoing curative or adjuvant (i.e. non-palliative) radiotherapy. SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 5 November 2019), the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 10) in the Cochrane Library (searched 5 November 2019), MEDLINE Ovid (1946 to 5 November 2019), Embase Ovid (1980 to 5 November 2019), Allied and Complementary Medicine (AMED) Ovid (1985 to 5 November 2019), Scopus (1966 to 5 November 2019), Proquest Dissertations and Theses International (1861 to 5 November 2019) and Web of Science Conference Proceedings (1990 to 5 November 2019). The US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases. SELECTION CRITERIA: We selected randomised controlled trials (RCTs) or quasi-RCTs of adult patients 18 years or older with head and neck cancer who had undergone curative or adjuvant radiotherapy to the head and neck, who had received an intervention to prevent the onset of ORN. Eligible patients were those subjected to pre- or post-irradiation dental evaluation. Management of these patients was to be with interventions independent of their cancer therapy, including but not limited to local, systemic, or behavioural interventions. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials from search results, assessed risk of bias, and extracted relevant data for inclusion in the review. Authors of included studies were contacted to request missing data. We used standard methodological procedures expected by Cochrane. MAIN RESULTS: Four studies were identified that met pre-determined eligibility criteria, evaluating a total of 342 adults. From the four studies, all assessed as at high risk of bias, three broad interventions were identified that may potentially reduce the risk of ORN development: one study showed no reduction in ORN when using platelet-rich plasma placed in the extraction sockets of prophylactically removed healthy mandibular molar teeth prior to radiotherapy (odds ratio (OR) 3.32, 95% confidence interval (CI) 0.58 to 19.09; one trial, 44 participants; very low-certainty evidence). Another study involved comparing fluoride gel and high-content fluoride toothpaste (1350 parts per million (ppm)) in prevention of post-radiation caries, and found no difference between their use as no cases of ORN were reported (one trial, 220 participants; very low-certainty evidence). The other two studies involved the use of perioperative hyperbaric oxygen (HBO) therapy and antibiotics. One study showed that treatment with HBO caused a reduction in the development of ORN in comparison to patients treated with antibiotics following dental extractions (risk ratio (RR) 0.18, 95% CI 0.43 to 0.76; one trial, 74 participants; very low-certainty evidence). Another study found no difference between combined HBO and antibiotics compared to antibiotics alone prior to dental implant placement (RR 3.00, 95% CI 0.14 to 65.16; one trial, 26 participants; very low-certainty evidence). Adverse effects of the different interventions were not reported clearly or were not important. AUTHORS' CONCLUSIONS: Given the suboptimal reporting and inadequate sample sizes of the included studies, evidence regarding the interventions evaluated by the trials included in this review is uncertain. More well-designed RCTs with larger samples are required to make conclusive statements regarding the efficacy of these interventions.

Determinants of Home Death in Patients With Cancer: A Population-Based Study in Ontario, Canada.

AIM: To determine factors associated with home death in patients with cancer in Ontario, particularly to assess the association between death at home and (1) patients' rural/urban residence and (2) neighborhood income in urban areas. MATERIALS AND METHODS: We conducted a retrospective cross-sectional study in Ontario (2003-2010) using linked administrative databases. In order to account for clustering phenomenon, multivariable generalized estimating equation model was used to evaluate factors associated with home death. Analysis was performed in both rural and urban areas. For urban areas, neighborhood income was tested as a determinant of the place of death. RESULTS: A total of 193 783 deaths were analyzed, 9.1% of which occurred at home. In urban areas, home death was more likely for patients living in richer neighborhoods (odds ratio 1.69 for the highest compared to lowest neighborhood income quintile, 95% confidence interval: 1.54-1.86). The odds of dying at home when living in a rural area were no different from those living in the poorest urban neighborhood. Other variables associated with lower odds of home death were comorbidity index, certain cancers, and year of death. CONCLUSION: The likelihood of dying at home significantly increases with living in higher-income urban neighborhoods and decreases with rural residence. Urban neighborhoods with lowest income have odds of home death similar to rural areas. These findings underline the importance of targeting proper populations for public support at the end of life.

Role of stereotactic body radiotherapy for symptom control in head and neck cancer patients.

PURPOSE: Our aim was to determine the efficacy and quality of life outcomes of head and neck (HN) stereotactic body radiotherapy (SBRT) in a palliative population with significant proportions of de novo HN tumors not amenable to surgery or protracted course of curative radiotherapy (RT). METHODS: A retrospective review of a prospective database identified 21 patients with 24 sites that were treated. Patients were treated with intensity modulated RT (IMRT), usually 7-9 static fields with a 2-3-mm margin from gross tumor volume to planning target volume only with no microscopic margin added. Electronic patient records and treatment plans were reviewed. Basic demographic information was collected. The EORTC QLQ-H&N35 questionnaire was the tool used to collect QOL data both pre- and on-treatment fraction 5. Univariate analysis was performed for predictors of local control (LC) and prognostic factors for overall survival (OS). RESULTS: A total of 21 patients had 24 sites that were treated. The median age was 87 (range 25-103) and median KPS was 70. The most common histology was squamous cell carcinoma (SCC) 19/24 (79 %), basal cell carcinoma (BCC) 3/24 (16 %), and melanoma (4 %). The median maximal diameter was 3.7 cm (range 1-10 cm). The most commonly treated site was lymph nodes in the neck 13/24 (54 %), skin 8/24 (33 %), 4/24 (16 %) other HN mucosal primary sites. Of the 24 lesions, 17 (71 %) were de novo, without prior treatment and 7/24 (29 %) were recurrent. The most commonly used dose/fraction (fx) was 40 Gy/5 (fx) (range 35/5fx-48/6fx). Of the 24 lesions, 6 (25 %) had complete response, 16/24 (67 %) had partial response, and 2/24 (8 %) had no response. Control was defined as no further progression after treatment. For the entire cohort, LC at 3, 6, and 9 months were 66, 50, and 33 %, respectively. In the de novo group, 2/16 (12.5 %) had local failures with the LC rate of 94, 94, and 87 % at 3 months, 6 months, and 1 year, respectively. In the recurrent group, 4/8 (50 %) had failure with LC rates of 87. 5, 62.5, and 50 % at 3 months, 6 months, and 1 year, respectively. Of the 21 patients, 10 died during follow up, with the OS rate at 3 months, 6 months, and 1 year of 90, 70, and 60 %, respectively. Being defined "de novo" showed a trend toward statistical significance p = 0.046 for local failure. Overall survival did not show significant difference between de novo and recurrent with a p value of 0.267. No significant prognostic variables for OS were found. Pre-treatment QOL scores for the entire cohort were 53/130 versus 38/130 (lower scores indicating better QOL) scores with a trend toward statistical significance p = 0.05. CONCLUSIONS: SBRT is efficacious with improved quality of life within this elderly frail population in the treatment of de novo and recurrent tumors of the head and neck with promising quality of life scores.

Hypofractionated Radiotherapy in Gynecologic Malignancies-A Peek into the Upcoming Evidence.

Radiotherapy (RT) has a fundamental role in the treatment of gynecologic malignancies, including cervical and uterine cancers. Hypofractionated RT has gained popularity in many cancer sites, boosted by technological advances in treatment delivery and image verification. Hypofractionated RT uptake was intensified during the COVID-19 pandemic and has the potential to improve universal access to radiotherapy worldwide, especially in low-resource settings. This review summarizes the rationale, the current challenges and investigation efforts, together with the recent developments associated with hypofractionated RT in gynecologic malignancies. A comprehensive search was undertaken using multiple databases and ongoing trial registries. In the definitive radiotherapy setting for cervical cancers, there are several ongoing clinical trials from Canada, Mexico, Iran, the Philippines and Thailand investigating the role of a moderate hypofractionated external beam RT regimen in the low-risk locally advanced population. Likewise, there are ongoing ultra and moderate hypofractionated RT trials in the uterine cancer setting. One Canadian prospective trial of stereotactic hypofractionated adjuvant RT for uterine cancer patients suggested a good tolerance to this treatment strategy in the acute setting, with a follow-up trial currently randomizing patients between conventional fractionation and the hypofractionated dose regimen delivered in the former trial. Although not yet ready for prime-time use, hypofractionated RT could be a potential solution to several challenges that limit access to and the utilization of radiotherapy for gynecologic cancer patients worldwide.

Systematic review of the predictors of positive margins in gastric cancer surgery and the effect on survival.

BACKGROUND: Complete resection is the only definitive treatment available for gastric cancer. Factors associated with positive margins and their survival effects have been the subject of many studies, but the appropriate management for these patients is still debated. The objective of this review is to examine positive margins after gastric cancer resections by exploring predictive factors, impact on survival, and optimal strategies for re-resection. METHODS: A systematic electronic literature search was conducted using Medline and EMBASE from January 1, 1998, to December 31, 2009. Studies on gastric or gastroesophageal junction adenocarcinoma that either investigated the predictors for positive margin or employed multivariate methods to analyze the survival effects of positive margins were selected. RESULTS: Twenty-two studies incorporating 19355 patients were included in this review. Positive margins were associated with larger tumor size, deeper wall penetration, more extensive gastric involvement, greater nodal involvement, higher stage, diffuse histology, higher Borrmann type, lymphatic vessel involvement, and total gastrectomy. Patient survival was independently associated with margin status, and this survival effect was more prominent in early cancers in most studies that performed subgroup analyses. CONCLUSIONS: The probability of acquiring positive margins is highly dependent on the biology and the extent of the tumor. There is a significant negative effect on survival, which is more prominent in cancers at early stages, making re-resection or a second operation important. Patients with more advanced disease can be offered more extensive surgery to remove disease, but this should be balanced against the risks of more extensive resections.

Primary gastrointestinal lymphoma.

BACKGROUND: Extranodal lymphoma may arise anywhere outside lymph nodes mostly in the gastrointestinal (GI) tract as non-Hodgkin's disease. We reviewed the clinicopathological features and treatment results of patients with primary GI lymphoma. MATERIALS AND METHODS: A total number of 30 cases with primary GI lymphoma were included in this study. Patients referred to the Radiation Oncology Department of Omid Hospital (Mashhad, Iran) during a 5-year period (2006-11). Clinical, paraclinical, and radiological data was collected from medical records of the patients. RESULTS: Out of the 30 patients with primary GI lymphoma in the study, 12 were female (40%) and 18 were male (60%) (male to female ratio: 3/2). B symptoms were present in 27 patients (90%). Antidiuretic hormone (LDH) levels were elevated in 9 patients (32.1%). The most common primary site was stomach in 14 cases (46.7%). Other common sites included small intestine and colon each in 8 patients (26.7%). All patients had histopathologically proven non-Hodgkin's lymphoma. The most common histologic subtype was diffuse large B-cell lymphoma (DLBL) in 16 patients (53.3%). In addition, 28 patients (93.3%) received chemotherapy with cyclophosphamide, vincristine, doxorubicin, prednisolone (CHOP regimen). The median course of chemotherapy was 6 cources. Moreover, 8 patients (26.7%) received radiotherapy with cobalt 60. The median follow-up time was 26 months. The overall 5-year survival rate was 53% and the median survival time was 60 months. CONCLUSION: Primary GI lymphoma is commonly seen in stomach and small intestine and mostly is DLBCL or mucosa-associated lymphoid tissue (MALT) lymphoma.

3'-Deoxy-3'-(18F) Fluorothymidine Positron Emission Tomography/Computed Tomography in Non-small Cell Lung Cancer Treated With Stereotactic Body Radiation Therapy: A Pilot Study.

Purpose: The primary objective was to compare 3'-deoxy-3'-(18F) fluorothymidine (FLT) positron emission tomography (PET)/computed tomography (CT) uptake in 3 cohorts of stereotactic body radiation therapy (SBRT) patients: (1) pre-SBRT, (2) stable post-SBRT lung fibrosis, and (3) suspicious or proven local recurrence post-SBRT. The secondary objectives were to optimize FLT-PET imaging by comparing FLT uptake in respiratory-gated (4-dimensional) versus nongated (3-dimensional) FLT-PET scans. Methods: Patients with early-stage non-small cell lung cancer planned or treated with SBRT at the institution with radiographic findings of fibrosis or recurrence were eligible for the study. All patients underwent imaging with FLT-PET/CT before SBRT in cohort 1 and at fibrosis or recurrence in cohort 2 and 3, respectively. The planned sample size was 20 patients in each cohort, with 60 patients total. FLT-PET standardized uptake value (SUV) variables including SUVmax, SUVmean, SUVpeak, SUV50, and SUV95 were compared among the 3 cohorts using the Kruskal-Wallis test. The correlation of respiratory-gated and nongated FLT-PET SUV variables was performed using the Spearman correlation coefficient. Results: Forty-one patients were recruited for the study (20 in cohort 1, 16 in cohort 2, and 5 in cohort 3) between 2015 and 2019. The majority received a diagnosis of stage I lung cancer (86%), and the most common prescription was 48 Gy in 4 fractions (59%). Respiratory-gated FLT-PET was performed in 35 patients. The FLT SUV variables were well correlated between respiratory-gated and nongated scans (r = 0.8-1.0). The SUVpeak, SUVmean, and SUVmax were significantly lower in the fibrosis cohort compared with the recurrence and pretreatment cohorts. The SUV50 and SUV95 values in the recurrence cohort were statistically similar to the pretreatment cohort. Conclusions: FLT-PET/CT may be helpful in differentiating SBRT-related fibrosis from recurrence. Nongated FLT-PET/CT with reporting of SUVmax and SUV95 values is recommended.

Immunohistochemical assessment of MGMT expression and p53 mutation in glioblastoma multiforme.

AIMS AND BACKGROUND: The prognosis of glioblastoma multiforme (GBM) remains poor despite advances in surgery and adjuvant therapies. TP53 and O6-methylguanine-DNA methyltransferase (MGM) are tumor suppressor genes that are implicated in GBM resistance to radiation and chemotherapy. In order to assess the expression of the protein products of these two genes, 50 GBM samples were analyzed in this study. METHODS: Demographic and clinical data along with postsurgery tumor samples from 50 GBM patients were collected from the pathology archive. MGMT and p53 protein expression was evaluated by immunohistochemistry. RESULTS: 52% of cases had mutated p53, predominantly expressed in the nuclei of tumor cells. MGMT immunohistochemistry was negative in 35 (70%) patients and positive in 15 (30%) others. Immunohistochemistry-negative specimens for MGMT expression showed a significantly higher expression of mutant p53 (P = 0.03). CONCLUSION: MGMT expression was significantly lower in cells bearing p53 mutation. This indicates that there is a tendency for p53 activity to decline with MGMT inactivation. However, this study could not deduce which protein was the regulator of the other.

Soluble Fas might serve as a diagnostic tool for gastric adenocarcinoma.

BACKGROUND: Fas (Apo-1/CD95) and its specific ligand (FasL) are key elements in apoptosis. They have been studied in different malignancies but there are few published studies about the soluble forms of these markers (i.e. sFas/sFasL) in gastric cancer. We have compared the serum levels of sFas/sFasL in gastric adenocarcinoma patients and cases with pre-neoplastic lesions as potential markers for early diagnosis, and investigated their relation with clinicopathological characteristics. METHODS: Fifty-nine newly-diagnosed cases of gastric adenocarcinoma who had undergone gastrectomy, along with 62 endoscopically- and histologically-confirmed non-cancer individuals were enrolled in this study. sFas/sFasL serum levels were detected by Enzyme Linked Immunosurbent Assay. RESULTS: Mean serum sFas level was significantly higher in gastric cancer patients than in control group (305.97 +/- 63.71 (pg/ml) vs. 92.98 +/- 4.95 (pg/ml), P < 0.001); while the mean serum level of sFasL was lower in patients with gastric adenocarcinoma (0.138 +/- 0.04 (pg/ml) vs. 0.150 +/- 0.02 (pg/ml), P < 0.001). Mean serum levels of sFas/sFasL were significantly different in both intestinal/diffuse and cardiac/non-cardiac subtypes when compared to the control group (P < 0.001). There was an increase in the serum level of sFas from the first steps of pre-neoplastic lesions to gastric adenocarcinoma (P < 0.001). Patients who had no lymph node involvement (N0) showed significantly higher serum levels of sFas compared to others (P = 0.044). CONCLUSIONS: Production of sFas may play a critical role in the carcinogenesis of intestinal-type gastric cancer. sFas serum level may serve as a non-invasive tool for early diagnosis of gastric cancer.

Radiation Boost After Adjuvant Whole Breast Radiotherapy: Does Evidence Support Practice for Close Margin and Altered Fractionation?

Adding a boost to whole breast radiation (WBI) following breast-conserving surgery (BCS) may help improve local control, but it increases the total cost of treatment and may worsen cosmetic outcomes. Therefore, it is reserved for patients whose potential benefit outweighs the risks; however, current evidence is insufficient to support comprehensive and consistent guidance on how to identify these patients, leading to a potential for significant variations in practice. The use of a boost in the setting of close margins and hypofractionated radiotherapy represents two important areas where consensus guidelines, patterns of practice, and current evidence do not seem to converge. Close margins were previously routinely re-excised, but this is no longer felt to be necessary. Because of this recent practice change, good long-term data on the local recurrence risk of close margins with or without a boost is lacking. As for hypofractionation, although there is guidance recommending that the decision to add a boost be independent from the whole-breast fractionation schedule, it appears that patterns-of-practice data may show underutilization of a boost when hypofractionation is used. The use of a boost in these two common clinical scenarios represents important areas of future study for the optimization of adjuvant breast radiation.

Should we embrace hypofractionated radiotherapy for cervical cancer? A technical note on management during the COVID-19 pandemic.

Cervical cancer is a deadly disease and the COVID-19 pandemic has the potential to further impact its lethality. Hypofractionated radiotherapy could mitigate this impact, however robust data in cervical cancer setting still is lacking. Information provided here could help institutions in reducing radiotherapy fractions for cervical cancer patients.

Comparison of CTVHR and organs at risk contours between TRUS and MR images in IB cervical cancers: a proof of concept study.

PURPOSE: To compare CTVHR and OAR dimensions and inter-rater agreement between magnetic resonance (MR) and trans-rectal ultrasound (TRUS) images in IB cervical cancer patients. METHODS: IB cervical cancer patients treated with (chemo)radiotherapy plus MR-guided brachytherapy (BT) were prospectively enrolled in this study. Radiation oncologists contoured CTVHR and OARs in pre-BT MR images (MRI) and intra-operative TRUS images. These contours were subsequently compared in regard to volume and dimension. Contour inter-rater agreement analysis was also investigated using kappa index (KI). Stata 15.0 was used for statistical analysis and a p-value < 0.05 was considered statistically significant. RESULTS: TRUS CTVHR volumes were statistically smaller than the respective MRI contoured volumes. TRUS CTVHR thickness was found to be consistently smaller than MRI contours in all patients. No statistical difference was seen in width and height between the two different imaging modalities. MRI contours had a median KI of 0.66 (range: 0.56-0.77) while TRUS-based contours had a median KI of 0.64 (range: 0.47-0.77). Bladder and rectum had very satisfactory KI in both imaging modalities. Vaginal contours had moderate agreement in MR (0.52) and in TRUS images (0.58). CONCLUSION: TRUS images allow good visualization of CTVHR and OARs in IB cervical cancer patients. Inter-rater contour variability was comparable between TRUS and MR images. TRUS is a promising modality on its own for image-guided BT.

A biochemical definition of cure after brachytherapy for prostate cancer.

BACKGROUND AND PURPOSE: To identify a PSA threshold value at an intermediate follow-up time after low dose rate (LDR) prostate brachytherapy associated with cure, defined as long-term (10-15 year) freedom from prostate cancer. MATERIALS AND METHODS: Data from 7 institutions for 14,220 patients with localized prostate cancer treated with LDR brachytherapy, either alone (8552) or with external beam radiotherapy (n = 1175), androgen deprivation (n = 3165), or both (n = 1328), were analyzed. Risk distribution was 42.4% favorable, 49.2% intermediate, and 8.4% high-risk. Patients with clinical failure before 3.5 years were excluded. Kaplan-Meier analysis was used with clinical failure (local, distant, regional or biochemical triggering salvage) as an endpoint for each of four PSA categories: PSA ≤ 0.2, >0.2 to ≤0.5, >0.5 to ≤1.0, and >1.0 ng/mL. PSA levels at 4 years (±6 months) in 8746 patients without clinical failure were correlated with disease status at 10-15 years. RESULTS: For the 77.1% of patients with 4-year PSA ≤ 0.2, the freedom-from-recurrence (FFR) rates were 98.7% (95% CI 98.3-99.0) at 10 years and 96.1% (95% CI 94.8-97.2) at 15 years. Three independent validation cohorts confirmed 97-99% 10-year FFR rates with 4-year PSA ≤ 0.2. Successive PSA categories were associated with diminished disease-free rates at 10 and 15 years. PSA category was strongly associated with treatment success (p < 0.0005). CONCLUSIONS: Since 98.7% of patients with PSA ≤ 0.2 ng/mL at 4 years after LDR prostate brachytherapy were disease-free beyond 10 years, we suggest adopting this biochemical definition of cure for patients with ≥4 years' follow-up after LDR brachytherapy.

Association between MGMT promoter hypermethylation and p53 mutation in glioblastoma.

O(6)-methylguanine-DNA methyltransferase (MGMT) is a DNA repair enzyme that removes alkyl groups from the O(6) position of guanine. MGMT is transcriptionally silenced by promoter hypermethylation in several human neoplasia. We used methylation-specific PCR (MSP) to analyze the MGMT promoter methylation status of 50 glioblastoma tumors. Hypermethylation was detected in 24 of 50 (48%) samples. We also analyzed mutant p53 expression by immunohistochemical analysis of glioblastoma tissue samples. A significant association was found between MGMT methylation and p53 mutation status (p< .05). These results suggested that epigenetic inactivation of MGMT plays an important role in the survival of glioblastoma patients and this inactivated gene involved in p53 mutation.

Comparison of pre-operative lymphoscintigraphy with inter-operative gamma probe and dye technique regarding the number of detected sentinel lymph nodes.

Sentinel lymph node (SLN) identification by lymphoscintigraphy (LS) and biopsy are the standard method for axillary lymph node staging in low stage breast cancer patients. Many previous studies did not compare the number of SLN on LS with SLN detected during surgery. We aimed to study the accuracy of pre-operative LS for the prediction of the number of SLN detected by surgical gamma probe and the dye technique during surgery. Sixty patients were included in our study. SLN biopsy was performed using the combined radioactive and blue dye methods. Patients without previous excisional biopsy of the tumor (45 patients) received periareolar intra-dermal injections of 17.5MBq/0.2mL technetium-99m-antimony sulfide colloid ((99m)Tc ASC). The remainder of the patients, with the history of excisional biopsy of the tumor (15 patients); received two intra-dermal injections of 17.5MBq/0.2mL (99m)Tc-ASC in both ends of the surgical incision. All injections were done 2-4 h before surgery and gentle massage was applied to the injection site. Results showed that the number of SLN was correctly detected by LS in 58 patients. Eighty SLN were totally detected during surgery. All these SLN were radioactive and could be identified by surgical gamma probe. No SLN was detected only by the blue dye. Of the 80 detected SLN, 60 (75%) were both radioactive and colored. Pre-operative LS correctly predicted the number of harvested SLN during surgery in 77.5% of the patients. Only 78.7% (63/80) of the total harvested SLN were detected by pre-operative LS. We conclude that pre- operative LS identifies 78.7% and the blue dye technique can identify 75% of the SLN found by the gamma probe during surgery. The pre-operative LS technique can correctly identify the number of SLN in 77.5% of the patients.

Outcomes following stereotactic radiosurgery for small to medium-sized brain metastases are exceptionally dependent upon tumor size and prescribed dose.

BACKGROUND: At our institution, we have historically treated brain metastasis (BM) ≤2 cm in eloquent brain with a radiosurgery (SRS) lower prescription dose (PD) to reduce the risk of radionecrosis (RN). We sought to evaluate the impact of this practice on outcomes. METHODS: We analyzed a prospective registry of BM patients treated with SRS between 2008 and 2017. Incidences of local failure (LF) and RN were determined and Cox regression was performed for univariate and multivariate analyses (MVAs). RESULTS: We evaluated 1533 BM ≤2 cm. Median radiographic follow-up post SRS was 12.7 months (1.4-100). Overall, the 2-year incidence of LF was lower for BM treated with PD ≥21 Gy (9.3%) compared with PD ≤15 Gy (19.5%) (sub-hazard ratio, 2.3; 95% CI: 1.4-3.7; P = 0.0006). The 2-year incidence of RN was not significantly higher for the group treated with PD ≥21 Gy (9.5%) compared with the PD ≤15 Gy group (7.5%) (P = 0.16). MVA demonstrated that PD (≤15 Gy) and tumor size (>1 cm) were significantly correlated (P < 0.05) with higher rates of LF and RN, respectively. For tumors ≤1 cm, when comparing PD ≤15 Gy with ≥21 Gy, the risks of LF and RN are equivalent. However, for lesions >1 cm, PD ≥21 Gy is associated with a lower incidence of LF without significantly increasing the risk of RN. CONCLUSION: Our results indicate that rates of LF or RN following SRS for BM are strongly correlated with size and PD. Based on our results, we now, depending upon the clinical context, consider increasing PD to 21 Gy for BM in eloquent brain, excluding the brainstem.

p16 promoter hypermethylation: a useful serum marker for early detection of gastric cancer.

AIM: To determine p16 promoter hypermethylation in gastric tumoral tissue and serum samples, its impact on p16-protein expression, and correlation with clinical and histological features. METHODS: Samples were obtained from 52 histologically confirmed cases of gastric adenocarcinoma. Gastric tissue and serum of 50 age- and sex-matched individuals with normal gastroscopy and biopsy were obtained as control samples. Methylation-specific polymerase chain reaction (MSP) was used to evaluate methylation status of p16 promoter. p16-protein expression was analyzed by immunohistochemical staining on paraffin-embedded sections. RESULTS: Methylation was detected in 44.2% (23/52) of tumoral tissues. 60.9% of them were also methylated in serum, i.e., 26.9% of all patients (14/52). Methylation was not detected in tissue and sera of control samples. p16-protein expression was decreased in 61.5% of cases (32/52), and was significantly associated with promoter hypermethylation (P < 0.001). Methylation was significantly more frequent in higher pathological grades (P < 0.05). Methylation was not associated with other clinicopathological features and environmental factors including H pylori infection and smoking. CONCLUSION: p16 promoter hypermethylation is an important event in gastric carcinogenesis. It is the principle mechanism of p16 gene silencing. It is related to malignant tumor behavior. Detection of DNA methylation in serum may be a biomarker for early detection of gastric cancer.

Expression of cell adhesion molecule CD44 in gastric adenocarcinoma and its prognostic importance.

AIM: To evaluate the relation of cluster of differentiation 44 (CD44) expression with clinicopathological features of gastric adenocarcinoma, and also its effect on prognosis with an emphasis on the differences between intestinal and diffuse types. METHODS: From 2000 to 2006, 100 patients with gastric adenocarcinoma, who had undergone total or subtotal gastrectomy without any prior treatment, were studied. Haematoxylin and eosin (HE) staining was used for histological evaluation, including the type (Lauren's classification) and grading of the tumor. The expression of CD44 in the gastric adenocarcinoma mucosa and the adjacent mucosa were determined by immunohistochemistry. The survival analysis was obtained using the Kaplan-Meier test. RESULTS: Of 100 patients, 74 (74%) patients were male. The tumors were categorized as intestinal type (78%) or diffuse type (22%). Sixty-five percent of patients were CD44-positive. CD44 expression was not detected in normal gastric mucosa. Rather, CD44 was more commonly expressed in the intestinal subtype (P=0.002). A significant relation was seen between the grade of tumor and the expression of CD44 (P=0.014). The survival analysis showed a poor prognosis of patients with CD44-positive tumors (P=0.008); and this was more prominent in the intestinal (P=0.001) rather than diffuse type. CONCLUSION: Cell adhesion molecule CD44 is highly expressed in gastric adenocarcinoma. CD44 expression is correlated with a poor prognosis in patients with the intestinal type of gastric adenocarcinoma. CD44 can, therefore, be utilized as a prognostic marker for this group of patients.

Curative Radiation Therapy at Time of Progression Under Active Surveillance Compared With Up-front Radical Radiation Therapy for Prostate Cancer.

PURPOSE: To describe and compare outcomes in men with initially presumed indolent prostate cancer receiving definitive radiation therapy after active surveillance (AS) versus those in a risk-matched cohort undergoing up-front radiation therapy. METHODS AND MATERIALS: Men prospectively enrolled in an AS program between 1992 and 2014 and subsequently undergoing curative radiation therapy (ie, image guided radiation therapy [IGRT] or low-dose-rate brachytherapy [LDR-BT]) were identified. Biochemical relapse-free rate (bRFR), metastasis-free rate (mFR), and overall survival (OS) were compared against a cohort of men treated up front, matched by age, clinical prognostic indices (risk group, prostate-specific antigen, cT category, Gleason score, percentage of involved biopsy cores), and radiation therapy modality. RESULTS: Of 1070 patients in the AS registry, 200 underwent definitive radiation therapy (143 IGRT and 57 LDR-BT) after a median of 32.9 (interquartile range [IQR] 20.6-59.8) months on surveillance. Main reasons for treatment were grade and volume upgrading (57.5% and 26%, respectively). Median follow-up after radiation therapy was 4.9 (IQR 3.1-7.5) years. At 5 years the bRFR, mFR, and OS were, respectively, 97%, 99%, and 98.5%. No patient died of prostate cancer. Adequate risk-matching was confirmed in an independent cohort comprising 359 patients receiving up-front IGRT (71%) or LDR-BT (29%) and followed for a median of 9 (IQR 3.1-7.5) years. There was no difference in the disease-specific outcomes (bRFR, mFR) between the 2 cohorts (Gray's P value of .257 and .934, respectively). In multivariate analyses, timing of radical radiation therapy (deferred vs up-front) was not correlated to biochemical relapse or metastases occurrence. CONCLUSIONS: Curative-intent radiation therapy (ie, dose-escalated IGRT or LDR-BT) after a period of AS renders excellent oncologic outcomes at 5 years. Deferring radical therapy after a period of AS does not seem to result in inferior oncologic outcomes compared with patients with similar risk characteristics undergoing up-front treatment.