Current Imaging Modalities Understage One-Third of Patients with Stage I Rectal Cancer: Implications for Treatment Selection

2018 ◽  
Vol 84 (10) ◽  
pp. 1589-1594
Author(s):  
Ahmed Dehal ◽  
Amanda N. Graff-Baker ◽  
Brooke Vuong ◽  
Daniel Nelson ◽  
Shu-Ching Chang ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Neoadjuvant Therapy ◽  
Surgical Resection ◽  
Stage I ◽  
Imaging Modalities ◽  
Clinical Staging ◽  
Kappa Index ◽  
Pathologic Stage ◽  
Appropriate Treatment ◽  
Pathologic Staging

Accurate preoperative clinical staging is essential to optimize the treatment of rectal cancer. Primary surgical resection is typically indicated for stage I disease, whereas neoadjuvant therapy is recommended for stages II and III. The objective of this study is to examine the accuracy of clinical staging using current imaging modalities in predicting pathologic stage and, thus, selecting appropriate treatment. Adult patients with nonmetastatic rectal cancer who underwent primary surgical resection were identified from the National Cancer Database between 2006 and 2014. Data on clinical and pathologic staging was obtained. Kappa index was used to determine the correlation between clinical and pathologic staging. A total of 13,175 patients were identified. The correlation between clinical and pathologic staging was 69 per cent for stage I (31% upstaged) (Kappa 0.54, P < 0.001). One-third of patients who were clinically staged as stage I, and were therefore treated with primary surgical resection, had pathologic stage II or III disease. Based on their clinical staging, those patients did not receive the neoadjuvant therapy recommended by present guidelines. Where accurate clinical staging is in doubt, oncologists should carefully examine the quality of staging modality and perhaps consider multimodal imaging using both endorectal ultrasound and MRI.

scholarly journals Prognostic Value of Clinical vs Pathologic Stage in Rectal Cancer Patients Receiving Neoadjuvant Therapy

2017 ◽  
Vol 110 (5) ◽  
pp. 460-466 ◽  
Author(s):  
Daniel Delitto ◽  
Thomas J George ◽  
Tyler J Loftus ◽  
Peihua Qiu ◽  
George J Chang ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Neoadjuvant Therapy ◽  
Cancer Patients ◽  
Prognostic Value ◽  
Pathologic Stage

scholarly journals Conditional Survival and Cure of Patients With Colon or Rectal Cancer: A Population-Based Study

2020 ◽  
Vol 18 (9) ◽  
pp. 1230-1237 ◽  
Author(s):  
Seyed M. Qaderi ◽  
Paul W. Dickman ◽  
Johannes H.W. de Wilt ◽  
Rob H.A. Verhoeven
Keyword(s):  
Rectal Cancer ◽  
Colon Cancer ◽  
Population Based ◽  
Stage I ◽  
Stage Iii ◽  
Disease Stage ◽  
Conditional Survival ◽  
Population Based Study ◽  
Pathologic Stage ◽  
Number Of Patients

Background: The increasing number of colorectal cancer (CRC) survivors need survival estimates that account for the time already survived. The aim of this population-based study was to determine conditional survival, cure proportions, and time-to-cure (TTC) of patients with colon or rectal cancer. Materials and Methods: All patients with pathologic stage I–III CRC treated with endoscopy or surgery, diagnosed and registered in the Netherlands Cancer Registry between 1995 and 2016, and aged 18 to 99 years were included. Conditional survival was calculated for those diagnosed before and after 2007. Cure proportions were calculated using flexible parametric models. Results: A total of 175,384 patients with pathologic stage I (25%), II (38%), or III disease (37%) were included. Conditional 5-year survival of patients with stage I, II, and III colon cancer having survived 5 years was 98%, 94%, and 92%, respectively. For patients with stage I–III rectal cancer, this was 96%, 89%, and 85%, respectively. Statistical cure in patients with colon cancer was reached directly after diagnosis (stage I) to 6 years (stage III) after diagnosis depending on age, sex, and disease stage. Patients with rectal cancer reached cure 0.5 years after diagnosis (stage I) to 9 years after diagnosis (stage III). In 1995, approximately 42% to 46% of patients with stage III colon or rectal cancer, respectively, were considered cured, whereas in 2016 this percentage increased to 73% to 78%, respectively. Conclusions: The number of patients with CRC reaching cure has increased substantially over the years. This study’s results provide valuable insights into trends of CRC patient survival and are important for patients, clinicians, and policymakers.

Stage I-II pediatric Hodgkin's disease: long-term follow-up demonstrates equivalent survival rates following different management schemes.

1990 ◽  
Vol 8 (7) ◽  
pp. 1128-1137 ◽  
Author(s):  
S S Donaldson ◽  
S J Whitaker ◽  
P N Plowman ◽  
M P Link ◽  
J S Malpas
Keyword(s):  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Survival Rates ◽  
Stage I ◽  
Management Policy ◽  
Clinical Staging ◽  
Pathologic Staging ◽  
Field Radiation ◽  
Extended Field

The results of treatment of 171 children with stage I-II Hodgkin's disease from two institutions with differing approaches to management have been analyzed. At the Stanford University Medical Center/Children's Hospital at Stanford (SUMC/CHaS), pathologic staging followed by extended-field radiation alone or involved-field radiation plus combination chemotherapy have been cardinal to the management policy. At St Bartholomew's Hospital/The Hospital for Sick Children at Great Ormond Street (Barts/GOS), clinical staging only has been used over the last 10 years, and involved/regional-field radiotherapy used as the treatment of choice rather than extended-field radiotherapy. Some children at each institution received combined modality therapy as primary management. Relapse among children with stage I disease was a more frequent occurrence in the Barts/GOS series than in the SUMC/CHaS group. However, the survival rates from the two centers are identical, 91% at 10 years. The following scientific-philosophic question is asked: Should one maximally stage and treat all children to increase the likelihood of a high freedom from relapse (FFR; cure) rate, or is it acceptable to minimize the initial staging and treatment, realizing that a proportion of patients will fail and require salvage/rescue therapy? With the awareness of morbidity from pathologic staging and aggressive treatment, and the favorable survival data reported from specialized centers using differing approaches, treatment strategies should be directed toward the long-term goal of cure of disease with maximal quality of life. A multidisciplinary management philosophy undertaken at a center with extensive experience in pediatric Hodgkin's disease is important to achieving this goal.

Room for improvement? The adoption of multimodal esophageal cancer care in the United States.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 78-78
Author(s):  
R. P. Merkow ◽  
K. Y. Bilimoria ◽  
M. McCarter ◽  
A. Stewart ◽  
W. B. Chow ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Neoadjuvant Therapy ◽  
Surgical Resection ◽  
Tumor Size ◽  
Locally Advanced ◽  
The United States ◽  
Stage I ◽  
Stage Ii ◽  
Cancer Data ◽  
Factors Associated

78 Background: Consensus guidelines recommend neoadjuvant chemo- or chemoradiation therapy as the preferred treatment for locally advanced esophageal adenocarcinoma; however, it is unknown if this recommendation has been widely adopted in the U.S. Our objective was to examine esophageal cancer multimodal therapy and identify factors associated with the use of neoadjuvant therapy. Methods: From the National Cancer Data Base, patients with middle third, lower third and GE junction (GEJ) adenocarcinomas were identified. Patients who were clinical stage I-III and underwent surgical resection were included. Separate logistic regression models were developed to identify predictors of neoadjuvant therapy utilization and outcomes. Results: From 1998 to 2007, 8,051 patients underwent surgical resection for esophageal cancer: 16.3% stage I, 45.0% stage II and 38.7% stage III. For stage II/III tumors, neoadjuvant use increased (49.0% to 77.8%, p<0.001). After adjustment, factors associated with underuse of neoadjuvant therapy in stage II/III patients were older age, Black or Hispanic ethnicity, more severe comorbidities, tumor location (GEJ and middle vs. lower third), tumor size ≥ 2cm, stage II (vs. III) and geographic region. Stage II/III patients not receiving neoadjuvant had an over two fold increased risk of positive lymph nodes (OR 2.14. 95% CI 1.79 – 2.55, p<0.001). In addition, the positive surgical margin rate increased almost three fold (OR 2.80 95% CI 2.17-3.62, p<0.001) but 30-day postoperative mortality risk was not significantly affected (OR 1.50 95% CI 0.94-2.39; p=0.090). For stage I patients, neoadjuvant therapy decreased over time (38.0% to 11.4%, p<0.001). The overuse of neoadjuvant therapy was associated with higher tumor grade, larger tumor size, and low surgical case volume (all p<0.05). Conclusions: The adoption of neoadjuvant therapy has increased in the past decade; however, opportunity exists to improve guideline treatment for locally advanced esophageal cancer. Registry-based feedback to individual hospitals, such as benchmark comparison tools, could help institutions provide care in concordance with national guidelines. No significant financial relationships to disclose.

Comparison of clinical and pathologic staging in esophageal cancer.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 31-31
Author(s):  
Anthony Joseph Scholer ◽  
Abhineet Uppal ◽  
Debopriya Ghosh ◽  
Mary Kledzik ◽  
Juan Santamaria-Barria ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Disease Free Survival ◽  
Clinical Staging ◽  
Tumor Characteristics ◽  
Kappa Index ◽  
Early Esophageal Cancer ◽  
Cross Sectional ◽  
Pathologic Staging ◽  
Endoscopy Ultrasound ◽  
N Staging

31 Background: Randomized trials have demonstrated improved disease-free survival for more advanced esophageal cancer treated with neoadjuvant chemo radiation (NCXRT). However, accurately treating a patient relies on the accuracy of pre-treatment T and N staging with endoscopy ultrasound and cross-sectional imaging, which is unknown, and can lead to over or under-treatment. Therefore, the objective of this study is to compare the clinical and pathologic staging in patients with early esophageal cancer that would be impacted by inaccurate clinical staging. Methods: Primary, non-metastatic esophageal cancer patients who had upfront esophagectomy without neoadjuvant CXRT between 2004 and 2013 were identified in the National Cancer database. The Kappa index was used to determine patient and tumor characteristics that effected concordance between clinical and pathologic T and N staging (p > 0.05 shows discordance). Results: Of 1810, 43 % of clinical T2 tumors were upstaged compared to 38% of T1 and 13% of clinical T2 were downstaged. Clinically positive N1 disease had the greatest concordance (91%) between clinical and pathologically staging, compared to clinical N0, where 57% were upstaged. Some patient groups significantly impacted the concordance rates of staging. T-Stage was less accurate (more discordant) in females (68%, kappa 0.41, p = 0.057) and Blacks (59%, kappa 0.023, p = 0.069) whereas overall N-stage was more discordant in Hispanics (83%, kappa, 0.67, p = 0.165). Conclusions: Accurate staging for esophageal adenocarcinoma can significantly impact the course of treatment. Upfront surgical resection of clinical T1 lesions and node negative tumors are at risk for under-treatment due to poor concordance with pathological stage, which may lead to decreased survival compared to a regimen of NCXRT. Clinicians should be aware of patient and tumor characteristics that increase the likelihood of discordance between clinical and pathologic staging when discussing treatment options for patients with esophageal cancer.

scholarly journals Should signet-ring cell histology alter the treatment approach for clinical stage I gastric cancer?

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 321-321
Author(s):  
Michael K. Turgeon ◽  
Adriana C. Gamboa ◽  
Manali Rupji ◽  
Rachel M. Lee ◽  
Jeffrey M. Switchenko ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Adjuvant Therapy ◽  
Neoadjuvant Therapy ◽  
Clinical Stage ◽  
Signet Ring Cell ◽  
Stage I ◽  
Perioperative Chemotherapy ◽  
Pathologic Stage ◽  
Signet Ring ◽  
Ring Cell

321 Background: Upfront surgery is standard of care for stage I gastric cancer. Despite this, many clinicians administer preoperative therapy for clinical stage I disease with signet ring cell histology, given its aggressive biology. We aimed to assess the validity of this practice. Methods: The National Cancer Database (2004-2015) was reviewed for pts with non-metastatic signet ring cell gastric cancer who underwent treatment with surgery alone, perioperative chemotherapy, neoadjuvant therapy, or adjuvant therapy. Analysis was stratified by preoperative clinical stage and pathologic stage. Primary outcome was overall survival (OS). Results: Of 3000 pts, median age was 61 (IQR: 51-70). 34% were clinical stage I (n = 1018) of which 53% received surgery alone (n = 542), 5% perioperative chemotherapy (n = 47), 12% neoadjuvant therapy (n = 125), and 30% adjuvant therapy (n = 304). Median follow-up was 26 mos. For clinical stage I disease, surgery alone was associated with improved median OS (108 mos) when compared to perioperative chemotherapy (80 mos), neoadjuvant therapy (41 mos), or adjuvant therapy (73 mos, all p < 0.001). For pathologic stage I, surgery alone had equivalent survival to perioperative and adjuvant therapy (5-yr OS: 81 vs 82 vs 79%, p = 0.22). Concordance between clinical and pathologic stage I was 56%, specifically, 41% of clinical stage I pts were upstaged to pathologic stage II (44%) and stage III (56%). Adjuvant therapy for these pts was associated with improved median OS compared to pretreatment (perioperative chemotherapy / neoadjuvant therapy) for those upstaged to pathologic stage II (122 vs 37mos, p < 0.001) or stage III (40 vs 18mos, p < 0.001) disease. Conclusions: Our stage-stratified study demonstrates improved survival with upfront surgery for clinical stage I signet ring cell gastric cancer. Despite 41% of clinical stage I pts being upstaged to stage II or III on final pathology, adjuvant therapy offers a favorable rescue strategy, with improved outcomes compared to those treated preoperatively. Surgery alone also affords similar survival for pathologic stage I disease compared to multimodal therapy. This study challenges the intrinsic bias to over-treat stage I signet ring cell gastric cancer.

Deferral of rectal surgery following a continued response to preoperative chemoradiotherapy (Watch and Wait) study: A phase II multicenter study in the United Kingdom.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 489-489 ◽  
Author(s):  
S. K. Yu ◽  
G. Brown ◽  
R. J. Heald ◽  
S. Chua ◽  
G. Cook ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Surgical Resection ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Neoadjuvant Chemoradiotherapy ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Clinical Staging ◽  
Pet Ct

489 Background: Neoadjuvant chemoradiotherapy (CRT) and surgical resection are standard components of therapy for patients locally advanced rectal cancer (T3,T4 or N+) in UK. In 15%-30% of patients treated pre-operatively with CRT will develop pathological complete response (CR). The time from completion of CRT to maximal tumour response is as yet unknown. This study is the first prospective study to attempt to identify the percentage of patients who can safely omit surgery and the safety of deferred surgery in patients who achieve clinical complete response post CRT. Of the 59 patients required for the study, this provides an update on 19 patients entered. Methods: Patients with locally advanced rectal cancer requiring neoadjuvant treatment are identified in the multidisciplinary meet (MDT). Patients undergo CRT using a minimum of 50.4Gy in 28 # daily conformal CT planned CRT with concomitant Capecitabine at 825mg/m2 BD. MRI pelvis and body CT are repeated 4 weeks post CRT and rediscussed at MDT. If there is a good partial response or CR, patients are considered for Deferral of Surgery Study. Based on the pre treatment clinical staging, patients are considered for adjuvant chemotherapy as per NICE guidance. At any point of the study, if there is histology proven tumour regrowth or progression, patient undergo surgery. Results: 10 (53%) patients remain in CR. 6 (32%) patients underwent surgical resection with clear margin after detection of tumour regrowth at from 2-23 months post CRT. 5 out of 6 of the patients with tumour regrowth underwent PET CT as per protocol, and all tumour regrowth in those 5 patients were detected by PET CT, i.e. FDG avid disease. The pathological stages on these 6 patients were ypT2N0 CRM negative in 5 and ypT3N0 CRM negative in 1. 3 (15%) patients with tumour regrowth refused surgery. Conclusions: In the 19 recruited patients, all the patients with tumour regrowth underwent surgical resection with clear margins. PET CT appears a useful tool for detecting tumour regrowth. The median time for tumour regrowth is 17.5 months post CRT. The trial will be successful if at least 11/59 patients are able to safely omit surgery. Accrual of patients continues. No significant financial relationships to disclose.

NRG-GI002: A phase II clinical trial platform for total neoadjuvant therapy (TNT) in rectal cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS3629-TPS3629 ◽  
Author(s):  
Thomas J. George ◽  
Greg Yothers ◽  
Theodore S. Hong ◽  
Marcia McGory Russell ◽  
Y. Nancy You ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Rectal Cancer ◽  
High Risk ◽  
Neoadjuvant Therapy ◽  
Surgical Resection ◽  
Phase Ii ◽  
Locally Advanced ◽  
High Risk Patient ◽  
Randomized Phase Ii ◽  
Total Neoadjuvant Therapy

TPS3629 Background: Improvements in outcomes for locally advanced rectal cancer (LARC) have plateaued due to an inability to consistently deliver adjuvant therapy (tx) and thus far ineffective novel therapies. Systematic testing of new chemotherapy and radiation sensitizers are needed to advance treatment outcomes. This randomized phase II modular clinical trial platform utilizes Total Neoadjuvant Therapy (TNT) with parallel experimental arms in LARC. The experimental arms are not intended for direct comparison, but to test a variety of sensitizers or hypotheses in a consistent and relatively homogenous high-risk patient (pt) population with correlative biomarkers. Success of any given experimental arm will be determined by achievement of pathologic endpoints compared to a control arm. Methods: This NCTN multi-arm randomized phase II trial serves as a modular platform to assess novel sensitizers to neoadjuvant chemotherapy and/or chemoradiotherapy (chemoRT) in LARC. Eligibility includes LARC as defined by any ONE of the following criteria: distal location (cT3-4 ≤5cm from the anal verge, any N); bulky (any cT4 or tumor within 3mm of the mesorectal fascia); high risk for metastatic disease (cN2); or not a candidate for sphincter-sparing surgical resection. After randomization, pts receive neoadjuvant FOLFOX x 4mo → chemoRT (capecitabine with 50.4Gy) → surgical resection 8-12 wks later. Based on promising phase I results, the first experimental arm will assess the activity of veliparib added to standard chemoRT (capecitabine + RT). Primary endpoint is to demonstrate improvement in Neoadjuvant Rectal Cancer (NAR) score for the experimental arm vs control representing 20% relative risk reduction in DFS HR and 3-4% absolute OS improvement. Secondary endpoints include comparisons of OS, DFS, toxicity, pCR, cCR, tx completion, negative surgical margins, sphincter preservation, sphincter function including quality of life, and exploratory assessments of molecular and radiographic predictors of response and distant failure. Target accrual is 79 evaluable pts per arm with additional arms added through rolling protocol amendments. NCT02921256. Support: U10 CA-180868, -20, 21, -22; UG-189867; AbbVie. Clinical trial information: NCT02921256.

Significant upstaging of patients with stage I pancreatic cancer from clinical to pathologic staging.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 349-349
Author(s):  
Heather Stuart ◽  
Caroline Ripat ◽  
Basem Azab ◽  
Danny Yakoub ◽  
Dido Franceschi ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Early Stage ◽  
Clinical Stage ◽  
Stage I ◽  
Clinical Staging ◽  
Early Stage Disease ◽  
Risk Of Mortality ◽  
Stage Disease ◽  
Pathologic Staging ◽  
Group 2

349 Background: Clinical staging of patients with pancreatic cancer is essential to determine if neo-adjuvant treatment, surgery or palliative treatment is required. Patients with early stage disease often receive upfront surgery, where as patients with more advanced disease often receive neo-adjuvant therapy. Therefore the accuracy of clinical staging significantly influences management decisions. This study investigates the correlation between clinical and pathologic staging for patients with stage I pancreatic cancer. Methods: A retrospective review of patients with pancreatic cancer in National Cancer Data Base from 1998-2006 was preformed. The clinical stage of patients with presumed stage I disease was compared to the postoperative pathologic stage. Cox proportional hazard ratio model and regression analysis were used to determine factors associated with mortality and upstaging, respectively. Results: 1697 patients with clinical stage I pancreatic cancer were divided into two groups. Group 1 was comprised of patients who were stage I postoperatively and Group 2 was comprised of patients that were upstaged to either stage II, III or IV postoperatively. There were 704 (41%) in group 1 and 993 (59%) in group 2. Within group 2, 595 (60%) were stage II, 321 (32%) were stage III and 77 (8%) were stage IV. Patients that were upstaged after surgery had an increased risk of mortality (HR 1.414, p < 0.001), whereas patients that received adjuvant chemotherapy had a decreased risk of mortality (HR 0.799, p < 0.001). Compared to Grade 1 tumors, Grade 2 and 3 tumors on biopsy were most likely to be upstaged on final pathology (p < 0.001). Conclusions: Patients with stage I pancreatic cancer are often candidates for upfront surgery, however this study demonstrates that a large number are upstaged on postoperative staging. Recognizing this may lead clinicians to administer neo-adjuvant treatment in a greater number of patients with early stage disease in order to optimize survival.

Patterns of adjuvant therapy use and survival outcomes in patients with rectal cancer not receiving neoadjuvant therapy in an Australian cohort.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 675-675
Author(s):  
Kate Jessica Wilkinson ◽  
Sharlyn Kang ◽  
Stephanie Hui-Su Lim ◽  
Cheok Soon Lee ◽  
Ray Asghari ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Adjuvant Therapy ◽  
Neoadjuvant Therapy ◽  
Surgical Resection ◽  
Real World ◽  
Survival Benefit ◽  
Cancer Specific Survival ◽  
Group A ◽  
Group B

675 Background: Consensus international guidelines recommend the use of neoadjuvant chemo-radiotherapy in patients with stage II-III rectal cancer. Despite this, due to factors including inaccurate/under-staging, patient co-morbidities and acute presentations, a proportion will undergo up-front surgical resection. The survival benefit of adjuvant therapy is unclear in this real world, non-trial population. Methods: A retrospective analysis of patients presenting with stage II-III rectal adenocarcinoma in South Western Sydney and Illawarra Shoalhaven Health Districts, Australia, between 2006 to 2015 was performed. Data was extracted from electronic health records, with institutional ethics approval. Treatment modalities, clinicopathological, recurrence and survival data were analyzed. The primary endpoint was overall survival (OS) by treatment modality. Results: 549 patients were identified, of which 295 (54%) underwent up-front surgical resection without neoadjuvant therapy. Of this cohort, 137 (46%) had no adjuvant therapy (Group A), 103 (35%) had adjuvant chemotherapy alone (Group B), and 55 (19%) had adjuvant radiotherapy +/- chemotherapy (Group C). Receipt of any adjuvant treatment was significantly associated with improved OS (5 year OS 56 vs. 79%, HR 0.44, 95% CI 0.3 – 0.6, p < 0.0001) and recurrence free survival (5 yr RFS 25% vs. 47%, HR 0.66, 95% CI 0.5 – 0.9, p=0.01), but not cancer specific survival (5yr CSS 75 vs. 80%, HR 0.78, 95% CI 0.5 – 1.3, p = 0.30). Group B had improved OS compared to Group A (5 yr OS 56% vs. 80%, HR 0.35, 95% CI 0.22 – 0.55, p < 0.0001). There was a trend to improved OS in Group C vs. Group A (5yr OS 56.0% vs. 69.2%, HR 0.79 95% CI 0.6 – 1.01, p = 0.052). The improved OS in Group B versus Group A remained significant in multivariate analysis (HR 0.41, 95% CI 0.22 – 0.77, p = 0.005). Conclusions: Adjuvant chemotherapy improved OS in this real world cohort, and there was a trend to a benefit with adjuvant chemo-radiotherapy. However, the lack of difference in cancer specific survival suggests that this benefit may be partly driven by patient selection bias. Further exploratory analyses to identify sub-groups deriving a cancer specific survival benefit are required.

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