Impact Of Tumor Characteristics Research Articles

Actionable mutational profiling in solid tumors using hybrid-capture-based next-generation sequencing in a real-world setting in Spain.

This study aimed to describe the performance of a next-generation sequencing (NGS) panel for the detection of precise genomic alterations in cancer in Spanish clinical practice. The impact of tumor characteristics was evaluated on informative NGS and actionable mutation rates. A cross-sectional study was conducted at the Fundación Jiménez Díaz University Hospital (May 2021-March 2022) where molecular diagnostic of 537 Formalin-Fixed Paraffin-Embedded (FFPE) tissue samples of diverse solid tumors (lung, colorectal, melanoma, gastrointestinal stromal, among others) was performed using AVENIO Tumor Tissue Targeted Kit. A descriptive analysis of the features of all samples was carried out. Multivariable logistic analysis was conducted to assess the impact of sample characteristics on NGS performance defined by informative results rate (for all tumors and for lung tumors), and on actionable mutations rate (for lung tumors only). AVENIO performance rate was 75.2% in all tumor samples and 75.3% in lung cancer samples, and the multivariable analysis showed that surgical specimens are most likely to provide informative results than diagnostic biopsies. Regarding the mutational findings, 727 pathogenic, likely pathogenic, or variant of unknown significance mutations were found in all tumor samples. Single nucleotide variant was the most common genomic alteration, both for all tumor samples (85.3% and 81.9% for all solid tumors and lung samples, respectively). In lung tumors, multivariable analysis showed that it is more likely to find actionable mutations from non-smokers and patients with adenocarcinoma, large cell, or undifferentiated histologies. This is the largest cohort-level study in Spain to profile the analyses of biopsy samples of different tumors using NGS in routine clinical practice. Our findings showed that the use of NGS routinely provides good rates of informative results and can improve tumor characterization and identify a greater number of actionable mutations.

Abstract PS12-22: Maintenance therapy with everolimus plus aromatase inhibitors vs aromatase inhibitors as after first-line chemotherapy in HR+/HER2- metastatic breast cancer: Updated analyses of the phase III randomized MAIN-A trial

Abstract Background Despite endocrine therapy is the mainstay of treatment for HR+/HER2- metastatic breast cancer (MBC), patients with high disease burden or those at risk of visceral crisis are still offered first-line chemotherapy (CT). Chemotherapy is generally followed by maintenance hormonal therapy. The MAIN-A study is an investigator-driven, randomized phase III trial designed to compare maintenance everolimus (EVE) combined with aromatase inhibitors (AI) versus AI alone in pts with disease control after first-line CT.Methods Postmenopausal pts achieving disease control (stable disease, partial response or complete response) after first-line CT were randomly assigned to EVE 10 mg po daily plus AI or to AI alone. Primary aim was PFS in the ITT. We present here overall survival (OS) results and the impact of tumor characteristics on PFS.Results 110 pts were randomized to EVE+AI (n=52) or to AI (n= 58). Primary aim results have been already presented (Guarneri V, ESMO Breast 2019), showing a non-significant prolongation of median PFS in the ITT population for EVE+AI (9.9 mos vs 7.2 mos, HR 0.764, 95% CI 0.501-1.164. Patients with visceral metastases tended to experience shorter PFS as compared with patients with patients with bone/soft tissues metastases (median 11.1 mos vs 6.4 mos, p=0.0746). The levels of estrogen receptor expression (>or< 50%) did not impact PFS, overall and by treatment arm. At the time of this writing, a total of 61 death events have been recorded. No difference in OS was observed between the two arms (median 33.9 mos for EVE+AI vs 33.5 mos for AI, HR 0.97, 95% CI 0.59-1.61).Conclusions Maintenance EVE+AI did not significantly impact on the outcome of metastatic breast cancer patients deemed suitable for first line chemotherapy. Citation Format: Valentina Guarneri, Saverio Cinieri, Maria Vittoria Dieci, Carmelo Bengala, Gabriella Mariani, Giancarlo Bisagni, Antonio Frassoldati, Claudio Zamagni, Laura Orlando, Carlo Alberto Giorgi, Gian Luca De Salvo, PierFranco Conte. Maintenance therapy with everolimus plus aromatase inhibitors vs aromatase inhibitors as after first-line chemotherapy in HR+/HER2- metastatic breast cancer: Updated analyses of the phase III randomized MAIN-A trial [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS12-22.

Impact of tumor characteristics and pre- and postoperative hormone levels on hormonal remission following endoscopic transsphenoidal surgery in patients with acromegaly.

Acromegaly is a disease of acral enlargement and elevated serum levels of insulin-like growth factor-1 (IGF-1) and growth hormone (GH), usually caused by a pituitary adenoma. A lack of consensus on factors that reliably predict outcomes in acromegalic patients following endoscopic endonasal transsphenoidal surgery (EETS) warrants additional investigation. The authors identified 52 patients with acromegaly who underwent an endoscopic endonasal approach (EEA) for resection of a GH-secreting pituitary adenoma. Preoperative and postoperative tumor and endocrinological characteristics such as tumor size, invasiveness, and GH/IGF-1 levels were evaluated as potential indicators of postoperative hormonal remission. Endocrinological remission was defined as postoperative IGF-1 levels at or below the age- and sex-normalized values. The 52 patients had a mean age of 50.7 ± 13.4 years and a mean follow-up duration of 24.4 ± 19.1 months. Ten patients (19%) had microadenomas and 42 (81%) had macroadenomas. Five patients (9.6%) had giant adenomas. Forty-four tumors (85%) had extrasellar extension, with 40 (77%) exhibiting infrasellar invasion, 18 (35%) extending above the sella, and 7 (13%) invading the cavernous sinuses. Thirty-six patients (69%) underwent gross-total resection (GTR; mean maximal tumor diameter 1.47 cm), and 16 (31%) underwent subtotal resection (STR; mean maximal tumor diameter 2.74 cm). Invasive tumors were significantly larger, and Knosp scores were negatively correlated with GTR. Thirty-eight patients (73%) achieved hormonal remission after EEA resection alone, which increased to 87% with adjunctive medical therapy. Ninety percent of patients with microadenomas and 86% of patients with macroadenomas achieved hormonal remission. Preoperative IGF-1 and postoperative day 1 (POD1) GH levels were inversely correlated with hormonal remission. Postoperative CSF leakage occurred in 2 patients (4%), and none experienced vision loss, death, or injury to internal carotid arteries or cranial nerves. Endoscopic transsphenoidal resection of GH-secreting pituitary adenomas is a safe and highly effective treatment for achieving hormonal remission and tumor control in up to 87% of patients with acromegaly when combined with postoperative medical therapy. Patients with lower preoperative IGF-1 and POD1 GH levels, with less invasive pituitary adenomas, and who undergo GTR are more likely to achieve postoperative biochemical remission.

The Prognostic Significance of Facial Nerve Involvement in Carcinomas of the Parotid Gland.

Facial nerve (FN) palsy and perineural invasion (PNI) are adverse features in carcinomas of the parotid gland. FN sacrifice at the time of surgery is associated with significant morbidity. The role of adjuvant radiotherapy in patients with high-risk features, including FN involvement, remains unclear. Analyze the disease-free survival (DFS) and overall survival (OS) and the impact of tumor characteristics, including FN involvement, for patients treated with surgical resection for carcinoma of the parotid gland. This is a retrospective chart review. University of Utah and Intermountain Healthcare, Utah. A total of 129 patients who were treated with primary surgery for nonmetastatic primary malignancies of the parotid gland from 1988 to 2006. Parotidectomy with or without adjuvant therapy. Kaplan-Meier analysis was used to obtain 5-year estimates of DFS and OS. Recurrence risk factors, particularly the impact of FN involvement, were analyzed. Five-year DFS and OS rates were 79% and 78%, respectively. Thirty-two (28%) patients developed recurrent disease. Disease recurrence occurred in 64% of patients with both FN palsy and PNI, in 43% with FN palsy without PNI, in 27% with only PNI, and in 16% without either feature. FN involvement, particularly FN palsy, is a predictor of increased risk of recurrence and death. Radiotherapy cannot substitute for FN sacrifice in high-risk patients.

Impact of selected tumor and patient characteristics on outcome of lymph node-positive breast cancer patients.

66 Background: Axillary lymph node (ALN) involvement remains the most significant factor affecting long term survival in breast cancer (BC) patients, and the risk of treatment failure is increased with the higher the number of ALN involvement, The aim of this study was to determine the impact of tumor characteristics; tumor size and number of positive lymph nodes and, ER and HER-2, as well as patient characteristics on DFS of patients with Lymph node positive Breast Cancer Patients who received Adjuvant Treatment. Methods: We retrospectively reviewed data of 704 patients with BC and ALN involvement who received adjuvant treatment in the period between 2010 and 2012. DFS outcomes were estimated with the Kaplan-Meier method and compared using the log rank test to determine. The effect of prognostic factors on BC outcomes. Results: Median age was 50 years (SD±12.024, Range 21-88). About 83.7% of the tumors were IDC,. About 30.4%of the tumors were grade III. Median tumor size was 5 cm (SD± 1.3745, Range 1-7).Median number of positive axillary LN was 4 (SD± 4.987, Range 1-37). Regarding receptor expression; 21.2% were HER-2 +ve, 58.7% were ER +ve and about 30.4 were triple negative. Median DFS was 20 months (SD± 14.511, Range 1-60). Cox regression showed that age, positive ER status and more than 3 ALN involvement had a statistically significant impact on DFS ( p<0.001 for all ), however, Tumor size, HER-2 overexpression, patient menstrual status had no significant effect. ER positive age >50 years was associated with prolonged DFS of 23 months (95%CI=20.641-25.359) versus 19 months (95% CI=17.598-20.402) for age≤50 years (p<0.001). ER positive status was associated with prolonged DFS of 22 months (95%CI=20.290-23.710) versus 17 months (95% CI=14.049-19.951) for ER negative (p<0.001).The group of patients with ≤3 positive dissected LN was associated with statistically significant prolonged DFS of 25 months (95%CI=22.286-27.714) versus 15 months (95%CI = 12.353-17.647) for patients with>3 positive dissected LN (p<0.001). Conclusions: These study indicate that the age, ER status and more than 3 ALN involvement have impact on DFS in Lymph node positive Breast Cancer Patients.

Major Perioperative Morbidity Does Not Affect Long‐Term Survival in Patients Undergoing Esophagectomy for Cancer of the Esophagus or Gastroesophageal Junction

The incidence of cancer of the esophagus/GE junction is dramatically increasing but continues to have a dismal prognosis. Esophagectomy provides the best opportunity for long-term cure but is hampered by increased rates of perioperative morbidity. We reviewed our large institutional experience to evaluate the impact of postoperative complications on the long-term survival of patients undergoing resection for curative intent. We identified 237 patients who underwent esophagogastrectomy, with curative intent, for cancer between 1994 and 2008. Complications were graded using the previously published Clavien scale. Survival was calculated using Kaplan-Meier methodology and survival curves were compared using log-rank tests. Multivariate analysis was performed with continuous and categorical variables as predictors of survival, and examined with logistic regression and odds ratio confidence intervals. There were 12 (5 %) perioperative deaths. The average age of all patients was 62 years, and the majority (82 %) was male. Complication grade did not significantly affect long-term survival, although patients with grade IV (serious) complications did have a decreased survival (p = 0.15). Predictors of survival showed that the minimally invasive type esophagectomy (p = 0.0004) and pathologic stage (p = 0.0007) were determining factors. There was a significant difference in overall survival among patients who experienced pneumonia (p = 0.00016) and respiratory complications (p = 0.0004), but this was not significant on multivariate analysis. In this single-institution series, we found that major perioperative morbidity did not have a negative impact on long-term survival which is different than previous series. The impact of tumor characteristics at time of resection on long-term survival is of most importance.

Preoperative C-Reactive Protein Level Adjusted for Comorbidities and Lifestyle Factors Predicts Overall Mortality in Localized Renal Cell Carcinoma

C-reactive protein (CRP), an acute phase reactant, is a non-specific marker of inflammation. Elevations in CRP levels are linked with trauma, infection, autoimmune disease, malignancy, and lifestyle factors, such as smoking and obesity. Previously, we noted a significant association between the preoperative CRP level, 1-year relapse-free survival, and 1-year overall relative survival in patients with localized renal cell carcinoma (RCC). This study sought to determine what effect, if any, lifestyle factors have on the prognostic value of preoperative CRP level for overall survival in individuals with localized RCC. 257 patients with localized RCC who underwent nephrectomy were included in the study. Patients were enrolled between November 2006 and February 2010. The impact of tumor characteristics, lifestyle factors, and preoperative CRP level on overall survival was assessed through univariate and multivariate analyses. During the study, 15.2% of patients died. Univariate analysis found that tumor size (p < 0.001), tumor stage (p < 0.001), Fuhrman nuclear grade (p < 0.001), Charlson Comorbidity Index score (p < 0.001), smoking status (p = 0.038), and preoperative CRP level (p < 0.001) were significantly associated with overall survival. Only the preoperative CRP level (odds ratio 1.035; 95% confidence interval 1.007, 1.064) remained significantly associated with overall survival upon multivariate analysis. Prognostic tools serve an important role in cancer management. Thirty percent of patients with localized RCC ultimately develop metastatic disease despite having potentially curative nephrectomy. Previous research has identified the preoperative CRP level as a significant predictor of overall survival in patients with localized RCC. This study demonstrated that the CRP level remained a robust predictive tool when the analysis was controlled for lifestyle factors, including smoking and obesity. Consequently, clinicians should consider taking preoperative CRP levels into account when treating patients with localized RCC.