EGFR and KRAS Mutations in the Non-Tumoral Lung. Prognosis in Patients with Adenocarcinoma

Tumor recurrence is frequent and survival rates remain extremely low in lung adenocarcinoma (ADC). We hypothesize that carcinogenic factors will promote loco-regional modifications not only in the future tumor, but throughout the exposed lung. Objective: To analyze whether the most prevalent mutations observed in ADC can also be observed in the non-neoplastic lung tissue, as well as the short-term prognosis implications of this finding. Methods: Non-tumoral lung parenchyma specimens obtained during surgery from 47 patients with EGFR and/or KRAS abnormalities in their ADC tumors underwent similar genomic testing. Short-term outcomes were also recorded. Results: The same mutations were present in the tumor and the histologically normal tissue in 21.3% of patients (SM group). Although local recurrences were similar in both groups, distant metastases were more frequent in the former (60 vs. 5.4%, p < 0.001). Moreover, SM patients showed lower time-to-progression (8.5 vs. 11.7 months, p < 0.001) and disease-free survival (8.5 vs. 11.2 months, p < 0.001). COX regression showed a higher risk of progression or death (DFS) in the SM group (HR 5.94, p < 0.01]. Similar results were observed when adjusting for potential confounding variables. Conclusions: These results confirm that genetic changes are present in the apparently normal lung in many ADC patients, and this finding has prognostic implications.

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Low-dose aspirin confers a survival benefit in patients with pathological advanced-stage oral squamous cell carcinoma

Scientific Reports ◽

10.1038/s41598-021-96614-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Sheng-Dean Luo ◽

Shao-Chun Wu ◽

Wei-Chih Chen ◽

Ching-Nung Wu ◽

Tai-Jan Chiu ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Oral Cavity ◽

Cell Carcinoma ◽

Squamous Cell ◽

Cox Regression ◽

Survival Rates ◽

Distant Metastases ◽

Good Prognosis ◽

High Rate

AbstractOral squamous cell carcinoma (OSCC) remains one of the most challenging clinical problems in the field due to its high rate of locoregional and distant metastases. However, studies that assess the association between aspirin use and survival in patients with OSCC are limited. Moreover, patients that recruited from those studies might have tumors that arose from different anatomic regions of the head and neck, including the oral cavity, oropharynx, etc. Since tumors within these distinct anatomic regions are unique in the context of epidemiology and tumor progression, we sought to evaluate the association of aspirin use with squamous cell carcinomas located within the oral cavity only. In this 10-year cohort study, we evaluated aspirin use and survival rates in relation to clinical characteristics as well as duration of aspirin use in patients with OSCC. Our findings suggest that OSCC patients with aspirin use for more than 180 days showed improved overall and disease-specific survival rates. Aspirin also improves survival in patients across various stages of OSCC. Cox regression models indicated that aspirin use was associated with a good prognosis. In conclusion, this evidence indicates that aspirin may be potentially used as an adjuvant therapy for OSCC.

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Prognostic impact of additive chemotherapy after curative resection of metachronous colorectal liver metastasis: a single-centre retrospective study

BMC Cancer ◽

10.1186/s12885-021-07941-2 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Matthias Kelm ◽

Julia Schollbach ◽

Friedrich Anger ◽

Armin Wiegering ◽

Ingo Klein ◽

...

Keyword(s):

Retrospective Study ◽

Curative Resection ◽

Randomized Clinical Trials ◽

Cox Regression ◽

Survival Rates ◽

Disease Free Survival ◽

Disease Recurrence ◽

Prognostic Impact ◽

Single Centre ◽

The Impact

Abstract Background A prognostic benefit of additive chemotherapy in patients following resection of metachronous colorectal liver metastases (CRLM) remains controversial. Therefore, the goal of this retrospective study was to investigate the impact of perioperative chemotherapy on disease-free survival (DFS) and overall survival (OS) of patients after curative resection of metachronous CRLM. Methods In a retrospective single-centre study, patients after curative resection of metachronous CRLM were included and analysed for DFS and OS with regard to the administration of additive chemotherapy. The Kaplan-Meier method was applied to compare DFS and OS while Cox regression models were used to identify independent prognostic variables. Results Thirty-four of 75 patients were treated with additive 5-FU based chemotherapy. OS was significantly prolonged in this patient subgroup (62 vs 57 months; p = 0.032). Additive chemotherapy significantly improved 10-year survival rates (42% vs 0%, p = 0.023), but not 5-year survival (58% vs 42%, p = 0.24). Multivariate analysis identified additive chemotherapy (p = 0.016, HR 0.44, 95% CI 0.23–0.86), more than five CRLM (p = 0.026, HR 2.46, 95% CI 1.16–10.32) and disease recurrence (0.009, HR 2.70, 95% CI 1.29–5.65) as independent risk factors for OS. Conclusion Additive chemotherapy significantly prolonged OS and 10-year survival in patients after curative resection of metachronous CRLM. Randomized clinical trials are needed in the future to identify optimal chemotherapy regimens for those patients.

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Patterns of failure and survival in patients with nasopharyngeal carcinoma treated with intensity modulated radiation therapy in Saudi Arabia.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.3_suppl.e295 ◽

2016 ◽

Vol 34 (3_suppl) ◽

pp. e295-e295

Author(s):

Ahmed M Maklad ◽

Yasser Bayoumi ◽

Mohamed Abdalaziz Senosy ◽

AbuSaleh A. Elawadi ◽

Hussain AlHussain ◽

...

Keyword(s):

Radiation Therapy ◽

Nasopharyngeal Carcinoma ◽

Distant Metastasis ◽

Cox Regression ◽

Intensity Modulated Radiation Therapy ◽

Disease Free Survival ◽

Distant Metastases ◽

Concurrent Chemotherapy ◽

Patterns Of Failure ◽

Intensity Modulated

e295 Background: We aimed to investigate the patterns of failure (locoregional and distant metastasis), associated factors, treatment outcomes in nasopharyngeal carcinoma (NPC) patients treated with intensity modulated radiation therapy (IMRT) combined with chemotherapy, results of reirradiation in recurrent cases and its toxicity. Methods: From April 2006 to December 2011, 68 NPC patients were treated with IMRT and chemotherapy at our hospital. Median radiation doses delivered to gross tumor volume (GTV) and positive neck nodes were 66–70 Gy/33-35fractions. For recurrent cases reirradiation was given by SRS 25 -30 Gy/5 fractions or IMRT 50-60 Gy/25-30 fractions according to volume of recurrence and surrounding critical structures. The clinical toxicities, patterns of failures, locoregional control (LRC), distant metastasis control (DMC), disease free survival (DFS) and overall survival (OS) were observed. Results: The median follow up time was 52.2 months (range: 11-87). EBV infection positive was 63.2%.There were 7 locoregional recurrences, 3 regional recurrences with distant metastases and 11 distant metastases. The median interval from the date of diagnosis to failure was 26.5 months (range, 16-50 months). 6/10 (60%) locoregional recurrences were treated with re-irradiation +/- concurrent chemotherapy. Acute grade 3 and 4 mucositis were observed in 2 patients (28.6%); however no significant late toxicities were seen after reirradiation. Nodal recurrences were salvaged by neck dissection. The 5-year LRC, DMC, DFS and OS rates of whole cohort were 81.1%, 74.3%, 60.1% and 73.4% respectively. Cox regression analyses revealed that neoadjuvant chemotherapy, age and Epstein-Barr virus (EBV) were independent predictors for DFS. Conclusions: Distant metastasis is the most common pattern of failure after IMRT with SIB technique with or without neoadjuvant and concurrent chemotherapy in Saudi patients with NPC. Early detection of local and locoregional recurrences is important as reirradiation with IMRT or SRT with or without chemotherapy is still feasible option with acceptable toxicity. However, efforts should be made for proper patient selection.

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Short Term Outcomes of Gastric Cancer at University Teaching Hospital of Kigali (CHUK), Rwanda.

10.21203/rs.3.rs-50726/v1 ◽

2020 ◽

Author(s):

Irénée Niyongombwa ◽

Irénée David Karenzi ◽

Isaie Sibomana ◽

Vital Muvunyi ◽

Jean Marie Vianney Kagimbangabo ◽

...

Keyword(s):

Gastric Cancer ◽

Survival Rate ◽

Mortality Rate ◽

Hospital Mortality ◽

Cox Regression ◽

Advanced Disease ◽

Survival Rates ◽

University Teaching ◽

Short Term ◽

The Mean

Abstract Background: Gastric cancer is the 4th most common cause of cancer death worldwide with an annual global incidence of 985,600; two thirds of them being in the developing countries. Gastric cancer is endemic in the so called stomach cancer region comprising Rwanda, Burundi, South Western Uganda and eastern Kivu province of Democratic Republic of Congo and its incidence in Rwanda is estimated around 13 to 15 per 100,000 population. To date, the outcomes of gastric cancer in the East African region are under investigated, and the survival rate in Rwanda is not known. The aim of this study was to describe the short term outcomes (in-hospital mortality rate, length of hospital stay, 3, 6, 12 and 24 months survival rates) in patients treated for gastric cancer at CHUK.Methods: We retrospectively reviewed the data collected from records of patients who consulted CHUK over a period of 10 years from September 2007 to August 2016. Patients were followed in hospital and after discharge for survival length. Descriptive statistics were used for baseline demographic data, Kaplan-Meier model and univariate cox regression were used for survival analysis.Results: Of the 199 patients enrolled in the study, 92 (46%) were males and 107 (54%) females. The mean age was 55.4 ranging between 24 and 93. The mean symptoms duration was 15 months. Most patients consulted with advanced disease, 62.3% with distant metastases. Treatment with curative intent was offered for only 19.9% of patients. The in-hospital mortality rate was 13.3%. The 3, 6, 12 and 24 months survival rate was 52%, 40.5%, 28% and 23.4% respectively. The Overall survival rate was 7 months.Conclusion: Patients with gastric cancer have delayed consultations and advanced disease at the time of presentation. This cancer is associated with poor outcomes in terms of hospital mortality and post discharge survival rates.

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Obstructive and perforative colonic carcinoma: patterns of failure.

Journal of Clinical Oncology ◽

10.1200/jco.1985.3.3.379 ◽

1985 ◽

Vol 3 (3) ◽

pp. 379-384 ◽

Cited By ~ 74

Author(s):

C Willett ◽

J E Tepper ◽

A Cohen ◽

E Orlow ◽

C Welch

Keyword(s):

Massachusetts General Hospital ◽

Survival Rates ◽

Disease Free Survival ◽

Distant Metastases ◽

Local Failure ◽

Colonic Carcinoma ◽

Control Group ◽

Free Survival ◽

Failure Patterns ◽

Disease Free

Carcinoma of the colon complicated by obstruction or perforation has been recognized as having a poorer prognosis than tumors without obstruction or perforation. To clarify the natural history, failure patterns, and implications for adjuvant treatment after resection with curative intent, a review of the recent Massachusetts General Hospital (MGH) experience was undertaken. From 1970 to 1977, 77 patients with obstructive colonic carcinoma and 34 patients with localized perforation at the tumor site were identified and compared with a control group of 400 patients without obstruction or perforation undergoing curative resection. All patients were observed for a minimum of five years or until the patient's death. The actuarial five-year survival and disease-free survival rates in patients with obstruction was 31% and 44%, respectively, in contrast to 59% and 75% in control patients. For patients with localized perforation, the five-year actuarial survival and disease-free survival rates were 44% and 35%, respectively. Of the 77 patients with obstructing tumors, 32 patients (42%) developed local failure--nine with local failure only and 23 patients with local failure and distant metastases. Thirty-four patients (44%) developed distant metastases. Fifteen (44%) patients of 34 with perforative colonic carcinoma had local failure. Distant metastases occurred in 15 patients (44%). The incidence of local failure and distant metastases in the control group was 14% and 21%, respectively. The rate of local failure and distant metastases increased with stage and was generally higher stage for stage than in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

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Retrospective analysis of 105 cases of uterine sarcoma

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.16079 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 16079-16079

Author(s):

A. Yoney ◽

S. Eskici ◽

B. Eren ◽

A. Salman ◽

M. Unsal

Keyword(s):

Therapeutic Option ◽

Survival Rates ◽

Disease Free Survival ◽

Distant Metastases ◽

Total Abdominal Hysterectomy ◽

Abdominal Hysterectomy ◽

Uterine Sarcoma ◽

Therapeutic Modality ◽

Uterine Sarcomas ◽

Pathologic Classification

16079 Background: Currently there is no randomized study based or widely accepted therapeutic modality in uterine sarcomas which are rare tumors forming a heterogeneous group in respect to their pathologic classification. Methods: In our trial, 105 pts. with uterine sarcoma who were referred to our clinic between years 1995–2003 have been retrospectively researched to evaluate the results in this tumor group. 43.8% had Leiomyosarcoma (LMS), 28.6% had Endometrial Stromal Sarcoma (ESS) and 27.6% had a Malign Mullarian Mixed Tumor (MMMT) while the distribution according to the histological subgroups were found to be 58.8% and 41.2% in low + middle grade tumors combined and in high grade tumors respectively. 76.2% had a Total Abdominal Hysterectomy + Bilateral Salphingooverectomy (TAH+BSO), 18.1% had a Total Abdominal Hysterectomy + Bilateral Salphingooverectomy + Lymphadenectomy (TAH+BSO+LND) and 5.7% had a suboptimal surgery as a surgical procedure. 38.1% of the pts. had Radiotherapy (RT), 18.1% had Chemotherapy (CT) and 12.4% had Chemo-radiotherapy (CT+RT) in addition to surgery. Results: The median age of the whole group is 51 (24–87). 55% of our pts. are under 50 years old and 68.5% had an “organ limited disease” ( stages I-II combined). The distant metastases rate is 30% and the local recurrence is 16.2%. All the local recurrences and 90% of the distant metastases have occurred within the first two years. The disease free survival rates at 3 and 5 years are 54.46% and 49.88% ; while the overall survival rates at 3 and 5 years are 54.63% and 51.09% all respectively. The stage is the most important factor effecting on the O.S and 5- year O.S rate is 68.43% in Stage I disease. Conclusions: The aggressive tumor progression pattern and the poor prognosis of uterine sarcomas require adjuvant therapies. The merit of current therapeutic options are still on debate since none of them has proved any specific effects. Planning further multi-center retrospective studies with high number of pts., a more clear description of the prognostic factors and thus the determination of the most appropriate therapeutic option is definitely needed. No significant financial relationships to disclose.

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Association Between Implementation Of Novel Therapies And Improved Survival In Patients Starting Hemodialysis: The Swedish Renal Registry 2006-2015

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa357 ◽

2020 ◽

Author(s):

Marie Evans ◽

Hong Xu ◽

Helena Rydell ◽

Karl-Göran Prütz ◽

Bengt Lindholm ◽

...

Keyword(s):

General Population ◽

Cox Regression ◽

Survival Rates ◽

Hemodialysis Patients ◽

Phosphate Binders ◽

Short Term ◽

Ultrafiltration Rate ◽

Risk Of Death ◽

Major Cardiovascular Events ◽

Laboratory Biomarkers

Abstract Background The recent years have witnessed significant therapeutic advances for patients on hemodialysis. We evaluated temporal changes in treatments practices and survival rates among incident hemodialysis patients. Methods Observational study of patients initiating hemodialysis in Sweden 2006-2015. Trends of hemodialysis-related practices, medications, and routine laboratory biomarkers were evaluated. The incidence of death and major cardiovascular events (MACE) across calendar years were compared against the age-sex-matched general population. Via Cox regression, we explored whether adjustment for implementation of therapeutic advances modified observed survival and MACE risks. Results Among 6,612 patients, age and sex were similar, but the burden of co-morbidities increased over time. The proportion of patients receiving treatment by hemodiafiltration, >3 sessions/week, lower ultrafiltration rate, and working fistulas increased progressively, as did use of non-calcium phosphate binders, cinacalcet, and vitamin D3. The standardized 1-year mortality decreased from 13.2% in 2006/07 to 11.1% in 2014/15. The risk of death decreased by 6% (HR 0.94, 95% CI 0.90-0.99) every two years, and the risk of MACE by 4% (HR 0.96; 0.92-1.00). Adjustment for changes in treatment characteristics abrogated these associations (HR 1.00; 0.92-1.09 for death and 1.00; 0.94-1.06 for MACE). Compared with the general population, the risk of death declined from 6 times higher 2006/2007 [standardized incidence rate ratio, sIRR 6.0 (5.3–6.9)], to 5.6 higher 2014/15 [sIRR 5.57 (4.8–6.4)]. Conclusions Gradual implementation of therapeutic advances over the last decade was associated with a parallel reduction in short-term risk of death and MACE among hemodialysis patients.

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Effects of Red Blood Cell Transfusions on Distant Metastases of Oral Squamous Cell Carcinomas

Cancers ◽

10.3390/cancers14010138 ◽

2021 ◽

Vol 14 (1) ◽

pp. 138

Author(s):

Leonard Simon Brandenburg ◽

Marc Christian Metzger ◽

Philipp Poxleitner ◽

Pit Jacob Voss ◽

Kirstin Vach ◽

...

Keyword(s):

Surgical Treatment ◽

Blood Cell ◽

Squamous Cell ◽

Red Blood Cell ◽

Cox Regression ◽

Cox Model ◽

Univariate Analysis ◽

Survival Rates ◽

Distant Metastases ◽

Patient Specific

There is no consensus on the effect of red blood cell (RBC) transfusions on patients with oral squamous cell carcinoma (OSCC). The aim of this study was to investigate the association between RBC administration and the occurrence of distant metastases (M+) after surgical treatment of OSCC. All medical records of patients who underwent primary surgery for OSCC in our department (2003–2019) were analyzed retrospectively (n = 609). Chi and Cox regression models were used to analyze the influence of transfusion on the development of M+, and survival rates. Kaplan–Meier curves were used for graphical presentation. A multitude of patient-specific factors showed a statistical impact in univariate analysis (transfusion, age, gender, diabetes, pT, pN, L, V, Pn, G, UICC, adjuvant therapy, free microvascular transplant, preoperative hemoglobin level). Transfusion status and pN stage were the only variables that showed a significant correlation to M+ in the multivariate Cox model. The hazard ratios for the occurrence of M+ were 2.42 for RBC transfusions and 2.99 for pN+. Administration of RBC transfusions was identified as a significant prognostic parameter for the occurrence of distant metastases after surgical treatment of OSCC. Hence, the administration of RBC transfusions should be considered carefully in the perioperative management.

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Short Term Outcomes of Gastric Cancer at University Teaching Hospital of Kigali (CHUK), Rwanda.

10.21203/rs.3.rs-50726/v2 ◽

2021 ◽

Author(s):

Irénée Niyongombwa ◽

Irénée David Karenzi ◽

Isaie Sibomana ◽

Vital Muvunyi ◽

Jean Marie Vianney Kagimbangabo ◽

...

Keyword(s):

Gastric Cancer ◽

Survival Rate ◽

Mortality Rate ◽

Hospital Mortality ◽

Cox Regression ◽

Advanced Disease ◽

Survival Rates ◽

University Teaching ◽

Short Term ◽

The Mean

Abstract Purpose: Gastric cancer is endemic in the so called stomach cancer region comprising Rwanda, Burundi, South Western Uganda and eastern Kivu province of Democratic Republic of Congo but its outcomes in that region are under investigated. This is the first study ever conducted in Rwanda with the purpose to describe the short term outcomes (in-hospital mortality rate, length of hospital stay, 3, 6, 12 and 24 months survival rates) in patients treated for gastric cancer. Methods: We retrospectively reviewed the data collected from records of patients who consulted CHUK over a period of 10 years from September 2007 to August 2016. Patients were followed in hospital and after discharge for survival length. Descriptive statistics were used for baseline demographic data, Kaplan-Meier model and univariate cox regression were used for survival analysis. Results: Of the 199 patients enrolled in the study, 92 (46%) were males and 107 (54%) females. The mean age was 55.4 ranging between 24 and 93. The mean symptoms duration was 15 months. Most patients consulted with advanced disease, 62.3% with distant metastases. Treatment with curative intent was offered for only 19.9% of patients. The in-hospital mortality rate was 13.3%. The 3, 6, 12 and 24 months survival rate was 52%, 40.5%, 28% and 23.4% respectively. The Overall survival rate was 7 months. Conclusion: In Rwanda, patients with gastric cancer have delayed consultations and advanced disease at the time of presentation. This cancer is associated with poor outcomes in terms of hospital mortality and post discharge survival rates.

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EGFR and KRAS Mutations in Lung Parenchyma of Subjects With EGFR/KRAS Wild-Type Lung Adenocarcinoma

Pathology & Oncology Research ◽

10.3389/pore.2021.598292 ◽

2021 ◽

Vol 27 ◽

Author(s):

Roberto Chalela ◽

Jose Gregorio González-García ◽

Karys Khilzi ◽

Víctor Curull ◽

Albert Sánchez-Font ◽

...

Keyword(s):

Progression Free Survival ◽

Lung Parenchyma ◽

Driver Mutations ◽

Normal Lung ◽

Kras Mutations ◽

Mutational Status ◽

Highly Sensitive ◽

Exon 19 Deletion ◽

Taqman Pcr

The acquisition of driver mutations in non-tumoral cells appears to be very important during the carcinogenesis of adenocarcinoma (ADC). Recent studies suggest that cancer-related mutations may not necessarily be present only in malignant cells, but also in histologically “healthy cells”.Objective: to demonstrate the presence of EGFR or KRAS mutations in non-tumoral lung cells in subjects with ADC and negative mutational status.Results: mutations in EGFR or KRAS oncogenes were identified in the normal lung in 9.7% of the subjects. Exon 21 substitution L858R in EGFR was detected in two cases while the exon 19 deletion E746-A750 in the EGFR, the G12C and G12D substitutions in the KRAS were detected once. One patient presented three different mutations in the normal lung parenchyma (EGFR_L858R, KRAS_G12C and KRAS_G12D). The negative-mutation status of the tumor and the mutations detected in the “normal lung” were confirmed using highly sensitive and specific TaqMan PCR (CAST-PCR). No differences were found in terms of progression, progression-free survival or overall survival during the 18 months follow-up.Conclusions: These results confirm the presence of driver mutations in the histologically normal lung parenchyma cells in the absence of mutations coexisting with the primary tumor.

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