Purpose
GANEA2 study was designed to assess accuracy and safety of sentinel lymph node (SLN) after neo-adjuvant chemotherapy (NAC) in breast cancer patients.
Methods
Early breast cancer patients ...treated with NAC were included. Before NAC, patients with cytologically proven node involvement were allocated into the pN1 group, other patient were allocated into the cN0 group. After NAC, pN1 group patients underwent SLN and axillary lymph node dissection (ALND); cN0 group patients underwent SLN and ALND only in case of mapping failure or SLN involvement. The main endpoint was SLN false negative rate (FNR). Secondary endpoints were predictive factors for remaining positive ALND and survival of patients treated with SLN alone.
Results
From 2010 to 2014, 957 patients were included. Among the 419 patients from the cN0 group treated with SLN alone, one axillary relapse occurred during the follow-up. Among pN1 group patients, with successful mapping, 103 had a negative SLN. The FNR was 11.9% (95% CI 7.3–17.9%). Multivariate analysis showed that residual breast tumor size after NAC ≥ 5 mm and lympho-vascular invasion remained independent predictors for involved ALND. For patients with initially involved node, with negative SLN after NAC, no lympho-vascular invasion and a remaining breast tumor size 5 mm, the risk of a positive ALND is 3.7% regardless the number of SLN removed.
Conclusion
In patients with no initial node involvement, negative SLN after NAC allows to safely avoid an ALND. Residual breast tumor and lympho-vascular invasion after NAC allow identifying patients with initially involved node with a low risk of ALND involvement.
Cancer immunotherapy has emerged as a transformative approach in cancer therapeutics, offering new hope to patients by harnessing the power of the immune system to target and eliminate cancer ...cells. It falls under the category of targeted therapy where an immune target i.e. molecule is identified and then immunotherapy i.e. antibodies are given to target it. Recent advances have brought a number of novel therapeutic options but they are also tagged with various challenges. These challenges include but not limited to the identification of appropriate target, later resistance to the therapy and most importantly the cost of the treatment.
The primary results of our phase II randomized trial suggested that compared with conventional preoperative chemoradiation (CRT), the addition of chemotherapy (CT) before CRT and surgery allows most ...patients receive their planned treatment with a better toxicity profile without compromising the pathological complete response and complete resection rates. We now report the 5-year outcomes.
Patients with distal or middle third, T3–T4 and/or N+ rectal adenocarcinoma selected by magnetic resonance imaging, were randomly assigned to arm A—preoperative CRT followed by surgery and four cycles of postoperative adjuvant capecitabine and oxaliplatin (CAPOX)—or arm B—four cycles of CAPOX followed by CRT and surgery. The following 5-year actuarial outcomes were assessed: the cumulative incidence of local relapse (LR) and distant metastases (DM), disease-free (DFS) and overall survival (OS).
A total of 108 eligible patients were randomly assigned to arm A (n = 52) or arm B (n = 56). With a median follow-up of 69.5 months, 5-year DFS was 64% in arm A and 62% in arm B (P = 0.85) and 5-year OS was 78% in arm A and 75% in arm B (P = 0.64). The 5-year cumulative incidence of LR was 2% and 5% (P = 0.61) and 5-year cumulative incidence of DM was 21% and 23%; (P = 0.79) in arms A and B, respectively.
Both treatment approaches yield similar outcomes. Given the lower acute toxicity and improved compliance with induction CT compared with adjuvant CT, integrating effective systemic therapy before CRT and surgery is a promising strategy and should be examined in phase III trials.
Early invasive ductal carcinoma (IDC) breast cancer often presents with a coexisting ductal carcinoma in situ (DCIS) component, while about 5 % of cases present with an extensive (>25 %) intraductal ...component (EIC). The impact of EIC on the genomic risk of recurrence is unclear.
Patients with early hormone receptor-positive HER2neu-negative (HR + HER2-) IDC breast cancer and a known OncotypeDX Breast Recurrence Score® (RS) who underwent breast surgery at our institute were included. Using a rule-based text-analysis algorithm, we analyzed pathological reports and categorized patients into three groups: EIC, non-extensive DCIS (DCIS-L), and pure-IDC (NO-DCIS). Genomic risk was determined using OncotypeDX RS.
A total of 33 (4.6 %) EIC cases, 377 (57.2 %) DCIS-L cases and 307 (42.8 %) NO-DCIS cases were identified. Patients in the EIC group were younger and had lower tumor grades than other groups. The distribution of genomic risk varied between the groups, with EIC tumors significantly less likely to have a high RS (>25) compared to DCIS-L and No-DCIS tumors (3 % vs 20 % and 20 %, respectively; p = 0.03). When adjusted to age, tumor size, grade and LNs involvement, both DCIS-L and NO-DCIS groups were significantly correlated with a higher probability of high RS compared to the EIC group (OR 12.3 and OR 13.1, respectively; p < 0.02). Moreover, patients with EIC had a lower likelihood for adjuvant chemotherapy recommendation.
In early HR + HER2- IDC, an EIC correlates with a reduced genomic recurrence risk. The impact on genomic risk seems to be influenced by the extent, not merely the presence, of DCIS.
•Invasive ductal carcinoma (IDC) breast cancer often presents with a coexisting ductal carcinoma in situ (DCIS) component.•About 5 % of cases present with an extensive (>25 %) intraductal component (EIC).•The presence of EIC is correlated with a lower Oncotype DX recurrence score (RS) compared to pure IDC.•The presence of coexisting non-extensive DCIS does not predict a lower genomic risk compared to pure IDC.•The use of an automatic rule-based text-analysis algorithm in pathology reports was efficient and valid.
There is no consensus regarding the optimal time to initiate adjuvant chemotherapy after surgery for stage III colon cancer, and the relevant postoperative complications that cause delays in adjuvant ...chemotherapy are unknown.
Eligible patients aged ≥66 years who were diagnosed with stage III colon cancer from 1992 to 2008 were identified using the linked Surveillance, Epidemiology, and End Results-Medicare database. Kaplan-Meier analysis and a Cox proportional hazards model were utilized to evaluate the impact of the timing of adjuvant chemotherapy on overall survival (OS).
A total of 18,491 patients were included. Delayed adjuvant chemotherapy was associated with worse OS (9-12 weeks: hazard ratio HR = 1.222, 95% confidence interval CI = 1.063-1.405; 13-16 weeks: HR = 1.252, 95% CI = 1.041-1.505; ≥ 17 weeks: HR = 1.969, 95% CI = 1.663-2.331). The efficacies of adjuvant chemotherapy within 5-8 weeks and ≤4 weeks were similar (HR = 1.045, 95% CI = 0.921-1.185). Compared with the non-chemotherapy group, chemotherapy initiated at ≥21 weeks did not significantly improve OS (HR = 0.882, 95% CI = 0.763-1.018). Patients with postoperative complications, particularly cardiac arrest, ostomy infection, shock, and septicemia, had a significantly higher risk of a 4- to 11-week delay in adjuvant chemotherapy (p < 0.05).
Adjuvant chemotherapy initiated within 8 weeks was acceptable for patients with stage III colon cancer. Delayed adjuvant chemotherapy after 8 weeks was significantly associated with worse OS. However, adjuvant chemotherapy might still be useful even with a delay of approximately 5 months. Moreover, postoperative complications were significantly associated with delayed adjuvant chemotherapy.
Tumour-associated macrophages (TAMs) are prominent immune cells infiltrating in solid tumours with phenotypic and functional heterogeneity. However, the clinical significance of heterogeneous ...subtypes of TAMs in gastric cancer still remains obscure. Here, we aimed to explore the clinical significance of TAMs expressing dendritic cell–specific intercellular adhesion molecule 3–grabbing non-integrin (DC-SIGN) and its relevance with immune contexture in gastric cancer.
We selected 453 formalin-fixed and paraffin-embedded samples and 51 fresh tissue specimens of patients with gastric cancer from Zhongshan Hospital. The association of DC-SIGN+ macrophages with clinicopathological parameters, overall survival (OS) and responsiveness to fluorouracil-based adjuvant chemotherapy (ACT) was inspected. Immunohistochemistry (IHC) and flow cytometry (FCM) were applied to characterize immune cells in gastric cancer.
We demonstrated that high intratumoral DC-SIGN+ macrophages infiltration predicted poor OS and inferior therapeutic responsiveness to fluorouracil-based ACT in patients with gastric cancer. Furthermore, higher infiltration of DC-SIGN+ macrophages indicated an increased number of Foxp3+ regulatory T cells (Tregs), CD8+ T cells and a higher ratio of Foxp3+/CD8+ within the tumour microenvironment (TME). In addition, CD8+ T cells in DC-SIGN+ macrophages high subgroup were functionally impaired, showing decreased interferon-γ (IFN-γ), granzyme B (GZMB) and perforin production yet elevated programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) expression.
DC-SIGN+ macrophages were associated with immunoinvasive TME and indicated poor prognosis and inferior therapeutic responsiveness to fluorouracil-based ACT. DC-SIGN+ macrophages might be an independent prognosticator and a potential immunotherapeutic target for gastric cancer.
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•Dendritic cell–specific intercellular adhesion molecule 3–grabbing non-integrin–positive (DC-SIGN+) macrophages predict adverse overall survival in gastric cancer (GC).•DC-SIGN+ macrophages attenuate responsiveness to fluorouracil-based adjuvant chemotherapy in GC.•DC-SIGN+ macrophages are associated with immune evasion in GC.•DC-SIGN+ macrophages are associated with exhausted CD8+ T cells in GC.•DC-SIGN+ macrophages are potential targets for immunotherapy in GC.
PURPOSE OF REVIEWThe value of adjuvant chemotherapy in rectal cancer is controversial with opinions varying from ‘not be used’ since randomized trials have not shown significant gains to ‘be used as ...in colon cancer’ as the need is the same and colon and rectal cancers are quite similar. This review will look upon data critically and with open eyes.
RECENT FINDINGSWith the exception of one randomized phase II trial (ADORE) revealing a significant gain in disease-free survival using one more effective regimen (mFOLFOX) than bolus 5-fluorouracil leucovorin, no new data have been presented. However, bringing up aspects in previous trials, either considered irrelevant for the present situation or overall negative, of what adjuvant treatment can achieve, a small reduction (hazard ratio about 0.8) in the risk of recurrence is present. This reduction is not fundamentally different from that in colon cancer considering that adjuvant treatment for rectal cancer cannot be initiated as rapidly as it can after a colon cancer diagnosis.
SUMMARYAdjuvant chemotherapy after rectal cancer surgery reduces recurrence risks but the benefit is limited and for most patients not clinically relevant. Neoadjuvant therapy can be more effective but results from randomized trials are not yet available.
Colon cancer (CC) is the second leading cause of cancer-related deaths in the United States. Quality measures have been introduced by the American Gastroenterological Association and Commission on ...Cancer for optimal management of CC. In this study, we sought to identify factors that may hinder the timely diagnosis and treatment of CC at a safety-net hospital system.
Retrospective chart review was performed for patients aged ≥18 y diagnosed with CC from 2018 to 2021. Primary outcomes were time from positive fecal immunochemical test to colonoscopy, time from diagnosis to surgery, and time from diagnosis to adjuvant chemotherapy. Secondary end points were demographic characteristics associated with suboptimal outcomes in any of the above measures.
One hundred ninety patients were diagnosed with nonmetastatic CC. The majority were Hispanic and non-English–speaking. 74.1% of patients with a positive fecal immunochemical test received a colonoscopy within 180 d. 59.6% of nonemergent cases received surgery within 60 d of diagnosis. 77% of those eligible received adjuvant chemotherapy within 120 d of diagnosis. No clinically significant demographic factor was associated with delay in colonoscopy, surgery, or adjuvant chemotherapy. Most frequent cause of delay in surgery (38.0%) was optimization of comorbidities. Most frequent cause of delay in adjuvant chemotherapy (71.4%) was delay in surgery itself.
No clinically significant demographic factor was associated with experiencing delays in diagnostic colonoscopy, surgery, or adjuvant chemotherapy.
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