Distant Disease-free Survival Research Articles

Incorporating weekly carboplatin in anthracycline and paclitaxel-containing neoadjuvant chemotherapy for triple-negative breast cancer: propensity-score matching analysis and TIL evaluation

BackgroundThe generation of data capturing the risk-benefit ratio of incorporating carboplatin (Cb) to neoadjuvant chemotherapy (NACT) for triple-negative breast cancer (TNBC) in a clinical practice setting is urgently needed. Tumour-infiltrating lymphocytes (TILs) have an established role in TNBC receiving NACT, however, the role of TIL dynamics under NACT exposure in patients receiving the current standard of care is largely uncharted.MethodsConsecutive TNBC patients receiving anthracycline-taxane [A-T] +/− Cb NACT at three Institutions were enrolled. Stromal-TILs were evaluated on pre-NACT and residual disease (RD) specimens. In the clinical cohort, propensity-score-matching was used to control selection bias.ResultsIn total, 247 patients were included (A-T = 40.5%, A-TCb = 59.5%). After propensity-score-matching, pCR was significantly higher for A-TCb vs A-T (51.9% vs 34.2%, multivariate: OR = 2.40, P = 0.01). No differences in grade ≥3 haematological toxicities were observed. TILs increased from baseline to RD in the overall population and across A-T/A-TCb subgroups. TIL increase from baseline to RD was positively and independently associated with distant disease-free survival (multivariate: HR = 0.43, P = 0.05).ConclusionsWe confirmed in a clinical practice setting of TNBC patients receiving A-T NACT that the incorporation of weekly Cb significantly improved pCR. In addition, A-T +/− Cb enhanced immune infiltration from baseline to RD. Finally, we reported a positive independent prognostic role of TIL increase after NACT exposure.

Role of postoperative chemoradiotherapy in head and neck cancer without positive margins or extracapsular extension: a propensity score-matching analysis

BackgroundThe aim of this work was to determine whether patients with intermediate-risk head and neck squamous cell carcinoma (HNSCC) can benefit from postoperative chemoradiotherapy (POCRT).MethodsPatients without extracapsular extension (ECE) or positive margins (PMs) who received POCRT or postoperative radiotherapy (PORT) at our center were retrospectively (December 2009 to October 2018) included for analysis, in particular, using a propensity score-matching method.ResultsAfter matching, 264 patients were enrolled, including 142 (41.2%) patients with pT3-4, 136 (38.3%) patients with pN2-3, 68 (21.1%) patients with perineural invasion, and 45 (12.8%) patients with lymphatic/vascular space invasion. With a median follow-up of 52 months, 3-year overall survival (OS), locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS) and disease-free survival (DFS) rates were 72.4%, 79.3%, 83.5% and 62.5%, respectively. pN2-3 was an independent risk factor for OS (p < 0.001), DFS (p < 0.001), LRFS (p < 0.001) and DMFS (p = 0.002), while pT3-4 was a poor prognostic factor for DMFS (p = 0.005). Overall, patients receiving POCRT had no significant differences from those receiving PORT in OS (p = 0.062), DFS (p = 0.288), LRFS (p = 0.076) or DMFS (p = 0.692). But notably, patients with pN2-3 achieved better outcomes from POCRT than PORT in 3-year OS (p = 0.050, 63.9% vs. 47.9%) and LRFS (p = 0.019, 74.6% vs. 54.9%). And patients with pT3-4 also had higher 3-year LRFS (p = 0.014, 88.5% vs. 69.1%) if receiving POCRT.ConclusionsAmong all intermediate-risk pathological features, pN2-3 and pT3-4 were independent unfavorable prognostic factors for patients with HNSCC without PMs or ECE. POCRT can improve the survival outcomes of patients with pN2-3 or pT3-4.

Development and validation of novel risk prediction models of breast cancer based on stanniocalcin-1 level.

The function of stanniocalcin-1 (STC-1) in the oncogenesis and progression of tumors has been extensively studied. The purpose of this study was to investigate the relationship between secreted STC-1 and prognosis in patients with breast cancer (BC) and to determine whether STC-1 could be a key prognostic factor in BC. The STC-1 level was measured by ELISA and clinical data from 1210 female patients with BC were used to develop and validate nomograms. We then verified the models through the plotting of ROC curves and calibration curves, calculating the C-index, and performing decision curve analyses (DCA). The level of STC-1 in the peripheral plasma was significantly correlated with the T stage, N stage, clinical stage, grade, hormone receptors, HER-2 status, and tumor subtype. Cox regression analyses revealed that estrogen receptor(ER) status, N stage, and STC-1 level were risk factors for overall survival (OS), whereas T stage, N stage, and STC-1 level were independent prognostic factors for distant disease-free survival (DDFS) and disease-free survival (DFS). Both the ROC curve and the C-index confirmed the high resolution of these models, while the DCA identified the feasibility of their practical application. In addition, the calibration curves indicated good consistency between the predicted and actual survival rates. Nomograms were created based on STC-1 levels for 3-, 5-, and 7-year OS, DDFS, and DFS of patients with BC respectively. As a key prognostic factor for BC, peripheral blood STC-1 level can be used clinically as a liquid biopsy indicator.

PSOR4 Presentation Time: 11:45 AM: Salvage High-Dose-Rate Brachytherapy for Prostate Cancer Local Recurrence: Comparison of Two Fractionation Schedules

<h3>Purpose</h3> Salvage high-dose-rate brachytherapy (sHDR-BT) is an efficient option administered for relapsing prostate cancer patients in our department since 2008. We decided to shorten and intensify our schedule with an equivalent total dose based on the available data in 2016. The aim is to compare two schedules of sHDR-BT in terms of efficacy. <h3>Materials and Methods</h3> A retrospective analysis of patients treated with sHDR-BT due to local recurrence (LR) of prostate cancer. All patients were treated with perineal interstitial HDR-BT under epidural or general anaesthesia in the lithotomy position. Schedule one ("3 × 10 Gy"; 2008-2016) consisted of three fractions of 10 Gy in 28 days, while schedule two ("2 × 13 Gy"; 2016-present) was two fractions of 13 Gy in 7-14 days. Biochemical recurrence was defined according to Phoenix criteria. Biochemical control (BC), local control (LC), distant metastasis-free survival (DMFS) and disease-free survival (DFS) were calculated. In statistical analysis, Kaplan-Meier estimator, log-rank test and Mann-Whitney U test were used. Two hundred thirty-three patients were enrolled in this analysis. Median age was 71 years (range: 42-84 years). Median follow-up was 44 months (range: 2-159). Median PSA max at recurrence was 2.9 ng/mL (range: 0.04-21.0 ng/mL). ISUP grade 1 was diagnosed in 15% of patients, 2 - in 17%, 3 - in 10%, ≥4 - in 16%, and in 42%, it was not determined. The comparison of groups with different fractionation revealed that patients in the "2 × 13 Gy" group were significantly older (p=0.04), their PSA level and Gleason score at recurrence were significantly higher (p=0.026 and p=0.044, respectively), the disease was more advanced (p=0.0000) and overall treatment time (OTT) was significantly shorter (p=0.0000). In the "3 × 10 Gy" group, there were 154 patients. Median age was 70 years (range: 42-80 years). Median follow-up was 62 months (range: 8-159 months). Median PSA max at recurrence was 2.7 ng/mL (range: 0.04-20.0 ng/mL). ISUP grade 1 was diagnosed in 17% of patients, 2 - in 18%, 3 - in 7%, ≥4 - in 12%, and in 45%, it was not determined. At the time of LR diagnosis, only one patient (0.65%) had regional lymph node metastases, and one patient (0.65%) had distant metastases. Both patients had oligometastases treated with SBRT. In the "2 × 13 Gy" group, there were 79 patients. Median age was 72 years (range: 55-80 years). Median follow-up was 24 months (range: 2-42 months). Median PSA max at recurrence was 3.2 ng/mL (range: 0.2-21.0 ng/mL). ISUP grade 1 was diagnosed in 11.4% of patients, 2 - in 13.9%, 3 - in 16.5%, ≥4 - in 24%, in 34.2% it was not determined. At the time of LR diagnosis, 73% of patients were diagnosed with LR only, 13% had regional lymph node metastases and 14% had distant metastases. All these patients had oligometastases treated with SBRT. <h3>Results</h3> In the whole group, median BC was 91 months, 2- and 5-year BC was 77% and 61%, respectively. Median LC was 108 months. Two- and 5-year LC was 93% and 76%, respectively. Median DMFS and DFS was 117 months and 70 months, respectively. Two- and 5-year DMFS was 86% and 71%, respectively; 2- and 5-year DFS was 81% and 67%, respectively. There was statistically significant difference in LC (p=0.017), DMFS (p=0.001) and DFS (p=0.0005) between "3 × 10 Gy" and "2 × 13 Gy" groups. Similar differences were observed between "OTT≤14 days" and "OTT>14 days" groups (p=0.011, p=0.01, p=0.004, respectively) (Table 1). <h3>Conclusions</h3> Salvage HDR-BT is an efficient treatment of localised prostate cancer relapse after primary irradiation. OTT>14 days and 3 × 10 Gy fractionation appear to be more effective in comparison to shorter OTT and 2 × 13 Gy fractionation. However, a longer follow-up is needed to confirm these findings, and a prospective trial would be of great value.

PL02 Presentation Time: 2:15 PM: Protocol-Based Re-Lumpectomy and Salvage Brachytherapy as Accelerated Partial Breast Re-Irradiation for In-Breast Tumor Recurrence After Whole Breast Irradiation: Long-Term Results

<h3>Purpose</h3> To analyze the clinical outcome of salvage lumpectomy and multi-catheter salvage brachytherapy for local recurrent breast tumor. <h3>Material and Methods</h3> Between 07/03 and 12/21, 76 patients with local recurrence after previous breast conserving surgery and whole breast irradiation underwent a protocol based re-lumpectomy and adjuvant salvage-brachytherapy as partial breast re-irradiation. We analyzed second local recurrent rates, distant metastasis rates, disease-free survival, and overall survival as primary objective, and late effects and cosmetic results as secondary objective. <h3>Results</h3> Median and mean follow-up after the salvage brachytherapy was 48 and 65 months, respectively [range: 8-198 months]. The 5y.- and 10y.-cumulative local 2^nd recurrence rates were 4.1% and 17.1%, respectively. Five and 10-year actuarial distant-metastasis rate were 7.7%. 5y.- and 10-year overall survival rates were 90.8% and 85.4%, respectively. As serious late side effects grade 3-4 we observed only fibrosis grade 3 by 8/76 patients (10.5%). <h3>Conclusion</h3> For patients with local in-breast recurrence after previous breast conserving surgery and whole breast irradiation is the re-lumpectomy plus salvage-brachytherapy as partial breast re-irradiation a reasonable and effective organ sparing treatment option, which is at least equivalent to results achieved with salvage mastectomy.

Comparison of Breast-Conserving Surgery vs. Mastectomy for Patients with Breast Cancer after Neoadjuvant Chemotherapy

<h3>Purpose/Objective(s)</h3> To compare recurrence and survival outcomes between breast-conserving surgery (BCS) and mastectomy after neoadjuvant chemotherapy (NACT). <h3>Materials/Methods</h3> A total of 730 eligible patients who underwent NACT between 2000 and 2014 were retrospectively reviewed. Of those, 104 (14.2%) patients received BCS and 626 (85.8%) patients received mastectomy. Locoregional recurrence (LRR), distant metastases (DM), disease-free survival (DFS), Breast cancer - specific survival (BCSS) and overall survival (OS) were estimated using the Kaplan-Meier method. The impact of BCS versus (vs) mastectomy on outcomes was assessed by multivariate Cox models and inverse probability of treatment weighting (IPTW) method by adjusting for age, clinical T stage, clinical N stage, NACT cycles, histological grade, lymphovascular invasion (LVI), molecular subtype/trastuzumab, ypT (pathologic tumor stage after NACT), ypN (pathologic lymph node stage after NACT), endocrine therapy, and adjuvant chemotherapy. Recurrence and survival curves before or after weighting were compared with the log rank test. <h3>Results</h3> The median follow-up was 87.4 months. The 5-year LRR, DM, DFS, BCSS and OS rates after BCS and mastectomy were 6.9% vs 7.6% (P = 0.805), 10.8% vs 19.9% (P = 0.145), 83.4% vs 78.2% (P = 0.514), 98.9% vs 90.4% (P = 0.005) and 98.9% vs 90.1% (P = 0.003), respectively. There were significant differences in distribution of most baseline characteristics between the BCS and mastectomy group. After IPTW adjustment, the clinical characteristics between two groups were comparable. Multivariate analysis showed that BCS had no significant impact on LRR (HR 1.08, 95% CI 0.48-2.43, P = 0.849), DM (HR 0.82, 95% CI 0.49-1.40, P = 0.473) and DFS (HR 1.12, 95% CI 0.70-1.80, P = 0.626) compared with mastectomy, but BCS significantly improved BCSS (HR 0.29, 95% CI 0.09-0.92, P = 0.035) and OS (HR 0.27, 95% CI 0.08-0.86, P = 0.027) compared with mastectomy. After IPTW adjustment, the results of 5-year LRR, DM, DFS remained the same, which were 10.0% vs 7.3% (P = 0.598), 11.7% vs 19.0% (P = 0.341), 78.6% vs 79.1% (P = 0.908) for BCS and mastectomy groups, respectively. The 5-year BCSS and OS were better in the BCS group than in the mastectomy group, but the difference was no longer statistically significant (BCSS: 99.7% vs. 90.8%, <i>P</i> = 0.095 and OS: 99.7% vs. 90.6%, <i>P</i> = 0.083). <h3>Conclusion</h3> Locoregional and distant control and DFS are comparable with BCS and mastectomy, but BCSS and OS may be better with BCS. Thus, BCS is a safe treatment option for selected breast cancer patients after NACT.

GLORIA: phase III, open-label study of adagloxad simolenin/OBI-821 in patients with high-risk triple-negative breast cancer.

Triple-negative breast cancer (TNBC) has the highest rate of distant metastasis and poorest overall survival among breast cancer subtypes. In a phase II study, adagloxad simolenin (AdaSim), a synthetic Globo H conjugate vaccine administered with adjuvant OBI-821, was shown to induce IgM and IgG anti-Globo H humoral responses in patients with metastatic breast cancer overexpressing the glycosphingolipid Globo H. GLORIA is an ongoing phase III, randomized, open-label clinical trial to evaluate the safety and efficacy of AdaSim and the quality of life (QoL) of patients receiving AdaSim plus standard of care (SOC) versus SOC alone in high-risk, early-stage TNBC. The primary end point is invasive progression-free survival; secondary end points include overall survival, QoL, breast cancer-free interval, distant disease-free survival, safety, and tolerability.

Overall survival in the OlympiA phase III trial of adjuvant olaparib in patients with germline pathogenic variants in BRCA1/2 and high-risk, early breast cancer

The randomized, double-blind OlympiA trial compared 1 year of the oral poly(adenosine diphosphate-ribose) polymerase inhibitor, olaparib, to matching placebo as adjuvant therapy for patients with pathogenic or likely pathogenic variants in germline BRCA1 or BRCA2 (gBRCA1/2pv) and high-risk, human epidermal growth factor receptor 2-negative, early breast cancer (EBC). The first pre-specified interim analysis (IA) previously demonstrated statistically significant improvement in invasive disease-free survival (IDFS) and distant disease-free survival (DDFS). The olaparib group had fewer deaths than the placebo group, but the difference did not reach statistical significance for overall survival (OS). We now report the pre-specified second IA of OS with updates of IDFS, DDFS, and safety. One thousand eight hundred and thirty-six patients were randomly assigned to olaparib or placebo following (neo)adjuvant chemotherapy, surgery, and radiation therapy if indicated. Endocrine therapy was given concurrently with study medication for hormone receptor-positive cancers. Statistical significance for OS at this IA required P < 0.015. With a median follow-up of 3.5 years, the second IA of OS demonstrated significant improvement in the olaparib group relative to the placebo group [hazard ratio 0.68; 98.5% confidence interval (CI) 0.47-0.97; P= 0.009]. Four-year OS was 89.8% in the olaparib group and 86.4% in the placebo group (Δ 3.4%, 95% CI-0.1% to 6.8%). Four-year IDFS for the olaparib group versus placebo group was 82.7% versus 75.4% (Δ 7.3%, 95% CI 3.0% to 11.5%) and 4-year DDFS was 86.5% versus 79.1% (Δ 7.4%, 95% CI 3.6% to 11.3%), respectively. Subset analyses for OS, IDFS, and DDFS demonstrated benefit across major subgroups. No new safety signals were identified including no new cases of acute myeloid leukemia or myelodysplastic syndrome. With 3.5 years of median follow-up, OlympiA demonstrates statistically significant improvement in OS with adjuvant olaparib compared with placebo for gBRCA1/2pv-associated EBC and maintained improvements in the previously reported, statistically significant endpoints of IDFS and DDFS with no new safety signals.

Impact of baseline telomere length on survival and chemotherapy related toxicity in breast cancer patients receiving (neo)adjuvant anthracycline containing chemotherapy

PurposeThe aim of this study is to assess baseline mean leukocyte telomere length (TL) as a potential predictive factor for chemotherapy toxicity and a prognostic marker for long-term outcome in early breast cancer (BC) patients. Methods445 BC patients were selected, diagnosed between 2007 and 2010 with early BC and treated with (neo)adjuvant fluorouracil, epirubicin and cyclophosphamide (FEC) or with FEC and Docetaxel (FEC-D). RT-qPCR was performed on germline DNA samples collected at diagnosis before any treatment, to measure mean leukocyte TL. Uni- and multivariable logistic regression or Cox proportional hazard regression analyses were carried out to assess correlation between baseline TL and toxicity parameters (derived from the medical chart) or longer-term outcome. ResultsBaseline TL correlated with age as expected (p = 0.005), but not with febrile neutropenia (n = 97), left ventricular ejection fraction >10% decrease (n = 17) nor other toxicity endpoints measured (all p > 0.05). TL was neither associated with overall survival, breast cancer specific survival or distant disease-free survival (all p > 0.05). ConclusionsBaseline TL is not associated with chemotherapy-related toxicity nor long-term outcome in BC patients.

Salvage Mastectomy Is not the Treatment of Choice for Aggressive Subtypes of Ipsilateral Breast Cancer Recurrence: A Single-Institution Retrospective Study.

Patients with triple-negative (TN) or human epidermal growth factor 2 (HER2)-enriched ipsilateral breast cancer recurrence (IBCR) seem to be excluded from a second breast-conserving surgery (BCS) under the assumption that salvage mastectomy would provide better oncological outcomes. The objective of this study was to describe the clinical features of these patients, to compare the two surgical alternatives (salvage mastectomy versus second BCS) in terms of oncological results, and to identify independent factors influencing prognosis and surgical treatment. We retrospectively reviewed all the consecutive patients with histologically confirmed TN or HER2-enriched IBCR. Disease-free survival (DFS), distant disease-free survival (DDFS), overall survival (OS), and breast cancer-specific survival (BCSS) were analyzed and compared between the two groups. Eighty-five patients were affected by TN or HER2-enriched IBCR. The majority of patients (72.9%) were treated with salvage mastectomy. There was no significant difference in terms of DFS between patients receiving a second BCS or mastectomy (p = 0.596). However, patients undergoing a second BCS had significantly better DDFS, OS and BCSS compared to mastectomy (p = 0.009; p = 0.002; p = 0.001, respectively). Tumor dimension <16 mm was found to significantly increase the probability of receiving a second BCS and positively affects recurrence and survival outcomes. Salvage mastectomy represents an independent poor prognostic factor for OS and BCSS. Salvage mastectomy is not always necessary and it does not seem to increase survival compared to a second BCS. In patients with small aggressive subtypes of IBCR, a second conservative approach can still be evaluated and offered, presenting acceptable loco-regional control and survival.

William Lindsay Morrison

Background/Aim: The value of androgen receptor (AR) in breast cancer has gained renewed interest as a prognostic and treatment predictive biomarker. The aims of this work were to study the...

Neoadjuvant durvalumab improves survival in early triple-negative breast cancer independent of pathological complete response

Addition of immune checkpoint inhibitors to neoadjuvant chemotherapy (NACT) is a promising strategy in early breast cancer, but the optimal duration of therapy is currently unknown. In the GeparNuevo (NCT02685059) trial, addition of durvalumab to NACT as previously reported led to a moderate increase in pathological complete response (pCR) rate by an absolute 9% (P= 0.287). Patients with cT1b-cT4a-d triple-negative breast cancer (TNBC) received durvalumab 1.5 g or placebo every 4 weeks added to nab-paclitaxel 125 mg/m2 weekly for 12 weeks, followed by durvalumab/placebo every 4 weeks plus epirubicin/cyclophosphamide every 2 weeks followed by surgery. Durvalumab was not continued after surgery. The primary objective was pCR. Secondary endpoints included invasive disease-free survival (iDFS), distant disease-free survival (DDFS) and overall survival (OS). A total of 174 patients were randomised between June 2016 and October 2017. After a median follow-up of 43.7 months, 34 events had occurred. Despite a non-significant increase in the pCR rate, significant differences were observed for 3-year iDFS, DDFS and OS: iDFS was 85.6% with durvalumab versus 77.2% with placebo [hazard ratio (HR) 0.48, 95% confidence interval (CI) 0.24-0.97, stratified log-rank P= 0.036]; DDFS 91.7% versus 78.4% (HR 0.31, 95% CI 0.13-0.74, P= 0.005); OS 95.2% versus 83.5% (HR 0.24, 95% CI 0.08-0.72, P= 0.006). pCR patients had 3-year iDFS of 95.5% with durvalumab and 86.1% without (HR 0.22, 95% CI 0.05-1.06). In the non-pCR cohort 3-year iDFS was 76.3% versus 69.7% (HR 0.67, 95% CI 0.29-1.54). Multivariable analysis confirmed a durvalumab effect independent of the pCR effect. No new safety signals occurred. Durvalumab added to NACT in TNBC significantly improved survival despite a modest pCR increase and no adjuvant component of durvalumab. Additional studies are needed to clarify the optimal duration and sequence of checkpoint inhibitors in the treatment of early TNBC.

CCNB2 expression correlates with worse outcomes in breast cancer patients: a pooled analysis

ABSTRACT Cyclin B2 (CCNB2) is upregulated in Breast Cancer (BC) and associated with worse relapse-free survival (RFS). However, its correlation with other clinical outcomes in BC was yet to be clarified. Therefore, this study aimed to explore the clinical significance of CCNB2 in BC. A comprehensive search was performed in PrognoScan and Gene Expression Omnibus (GEO) databases by searching the keywords of CCNB2 and breast cancer. Pooled hazard ratios (HRs) of overall survival (OS), relapse-free survival (RFS), distant metastasis-free survival (DMFS), disease-specific survival (DSS), and disease-free survival (DFS), and their corresponding 95 percent confidence intervals (CI) were calculated. Sensitivity analysis by omitting one study at a time and publication bias assessment by Egger’s test and Begg’s test were conducted. The clinical outcomes were externally verified via Kaplan-Meier Plotter. All of the statistical analyses were performed through STATA 17.0, and P values of less than 0.05 were taken to be statistically significant. Seven records with 1,074 participants were included for OS, with HR of 1.71 (95 percent CI = 1.24–2.35). Verification through Kaplan-Meier Plotter online tool based on 1,897 patients showed an HR of 1.75 (95 percent CI = 1.45–2.12, P < .01). For RFS, 11 records with 1,253 participants were included with the pooled HR of 1.37 (95 percent CI: 1.10–1.71). Verification based on 4,929 patients found and HR of 1.97 (95 percent CI = 1.78–2.19, P < .01). Regarding DMFS, the pooled HR of 10 records with 1,395 participants was 1.60 (95 percent CI: 1.24–2.05) and verification based on 2,765 patients revealed an HR of 1.97 (95 percent CI = 1.68–2.31, P < .01). For DSS, four records with 689 participants were included for DSS, with HR of 1.38 (95 percent CI = 0.59–3.24). The HR of DFS was 1.60 (95 percent CI: 0.46–5.51) after pooling 3 records with 379 participants. High expression of CCNB2 in BC is associated with worse OS, RFS, and DMFS, but not with DSS and DFS. More well-designed studies from different populations and different BC types are still needed.

Preoperative chemoradiotherapy with capecitabine and triweekly oxaliplatin versus capecitabine monotherapy for locally advanced rectal cancer: a propensity-score matched study

BackgroundDistant metastasis has been the main failure pattern for locoregionally advanced rectal cancer (LARC) patients, and intensified neoadjuvant chemotherapy has become a popular research topic. The present study aimed to compare the survival outcomes, acute toxicities and surgical complications in LARC patients who received preoperative chemoradiotherapy with triweekly oxaliplatin and capecitabine (triweekly XELOX) or capecitabine.Methods: Between 2007 and 2017, patients with clinically staged II-III rectal cancer who were treated with preoperative chemoradiotherapy using either triweekly XELOX (oxaliplatin 130 mg/m2 plus capecitabine 825 mg/m2) or capecitabine were included. Variables potentially influencing chemotherapy treatment selection were used to generate propensity scores (PS). The association between chemotherapy regimens and survival endpoints, including distant metastasis-free survival (DMFS), overall survival (OS) and disease-free survival (DFS), were evaluated and adjusted with PS. The acute toxicities and surgical complications were also compared.ResultsA total of 810 patients were included in the analysis; 277 (34.2%) patients received triweekly XELOX, and 533 (65.8%) received capecitabine. The pathological complete response (pCR) rates were 20.2 and 19.9% (P = 0.912) for the groups treated with triweekly XELOX and capecitabine, respectively. The 5-year DMFS, OS and DFS with triweekly XELOX versus capecitabine were 75.6% vs. 77.6% (P = 0.555), 79.2% vs. 83.3% (P = 0.101), and 69.9% vs. 73.7% (P = 0.283), respectively. Triweekly XELOX was not associated with an increased risk of severe toxicity during chemoradiotherapy, but it increased the risk of postoperative complications compared to capecitabine. After PS adjustment, the differences between the two groups remained insignificant in pCR rate, survival outcomes, and acute toxicities, and the difference in surgical complications disappeared.ConclusionsTriweekly XELOX or capecitabine concurrent with neoadjuvant radiotherapy leads to similar long-term survival outcomes, acute toxicities and surgical complications in LARC patients.

Characteristics and oncological results of epidermoid anal carcinoma: Comparison analysis between immunocompetent and immunosuppressed patients

ObjectiveMost evidence, including recent randomized controlled trials, analysing anal squamous cell carcinoma (SCC) do not consider immunocompromise patient population. The aim of this study was to compare clinical and oncological outcomes among immunocompetent and immunocompromised patients with anal squamous cell carcinoma. MethodMulticentric retrospective comparative study including 2 cohorts of consecutive patients, immunocompetent and immunocompromised, diagnosed with anal SCC. This study evaluated clinical characteristics, clinical response to radical chemoradiotherapy (CRT) and long-term oncological results including both local and distant recurrence, overall survival (OS) and disease-free survival (DFS). ResultsA total of 84 patients, 47 (55.6%) female, diagnosed with anal SCC from January 2012 to December 2017 were included, 22 (26%) and 62 (74%) patients in immunocompromised and immunocompetent groups respectively. Patients in immunocompromised group were significantly younger (53 vs. 61 years; P = 0.001), with smaller tumoral size (P = 0.044) and reported higher rates of substance abuse including tobacco use (P = 0.034) and parenteral drug consumption (P = 0.001). No differences were found in administered therapies (P = 301) neither in clinical response to chemoradiotherapy (83 vs. 100%). Moreover, similar 5-year OS (60 vs. 64%; P = 0.756) and DFS (65 vs. 68%; P = 0.338) were observed. ConclusionThe present study shows no significant differences in long-term oncological results among immunocompetent and immunocompromised patients diagnosed with anal SCC, with a similar oncologic treatment. This evidence might be explained due to the close monitoring and adequate therapeutic control of HIV positive patients.

Chest wall resection for breast cancer: 21st century Mayo clinic experience.

We hypothesized full-thickness chest wall resection (FTCWR) with advanced surgical techniques and modern systemic therapy is safe, provides local control, and good overall survival. Retrospective review of FTCWR (including rib or part of sternum) for breast cancer between 2000 and 2020. Primary endpoints included 90-day morbidities and all-cause mortality. Secondary endpoints were loco-regional and distant recurrence, DFS andoverall survival (OS). A total of 35 patients met the criteria. 34 FTCWR were for recurrence and the median time to chest wall recurrence was 6 years. Tumor subtype was triple-negative in 51% and the remainder HR+ Her2-. 58% were palliative resections. FTCWR included rib(s) in 89% and portion of sternum in 57%; 94% required reconstruction and 80% were R0 resections. There were no 90-day mortalities. Overall morbidity was 10/35(28%). 17(49%) patients received neoadjuvant systemic therapy for their recurrence and three received neoadjuvant radiation. Adjuvant treatment included chemotherapy (8), endocrine therapy (3), and both (8). Ten patients (28%) received adjuvant radiation. The Median follow-up was 31 months and there were 6 (17%) loco-regional and 7 (20%) distant recurrences. OS was 86% and 67% at 1 and 3 years, respectively. FTCWR was associated with low morbidity, mortality, recurrence rates, and good OS. Selective FTCWR is safe and has acceptable short-term survival rates.

Surgical Options for Ipsilateral Breast Tumor Recurrence: Mastectomy Versus Repeat Breast-Conserving Surgery

Purpose: The standard care for patients with ipsilateral breast tumor recurrence (IBTR) after breast-conserving surgery (BCS) is a total mastectomy (TM); however, there is growing interest in repeating BCS for IBTR.Methods: We retrospectively analyzed patients with IBTR who underwent initial BCS for breast cancer at our institution between January 2000 and December 2018. The Kaplan-Meier method was used to compare survival rates between the standard BCS-TM treatment group and the repeat-BCS group.Results: We enrolled 209 IBTR patients with a median follow-up of 102.3 months. No significant differences were observed in overall survival (10 years: 87.3% vs. 78.8%; hazard ratio [HR], 1.11; 95% confidence interval [CI], 0.44-2.81; p=0.821), distant metastasis free survival (10 years: 73.9% vs. 77.7%; HR, 0.80; 95% CI, 0.37-1.72; p=0.727) and disease-free survival (10 years: 57.1% vs. 65.2%; HR, 0.63; 95% CI, 0.35-1.12; p=0.115) between two groups. Repeat-BCS group showed significantly poorer locoregional recurrence free survival rate than did the TM group (HR, 2.44; 95% CI, 1.06-5.56; p=0.029) but the significance was not shown after excluding ipsilateral breast tumor recurrence events.Conclusion: No significant differences were observed in survival outcomes and recurrence rates between patients with IBTR who underwent mastectomy or repeat BCS regardless of molecular subtype, except secondary IBTR rates.

Prognostic and Biologic Significance of ERBB2-Low Expression in Early-Stage Breast Cancer

It is unclear whether ERBB2-low breast cancer should be considered an individual biologic subtype distinct from ERBB2-0 breast cancer. To investigate whether low ERBB2 expression is associated with distinct clinicopathologic characteristics and prognosis among patients with hormone receptor (HR)-positive and triple-negative breast cancer (TNBC). This cohort study was conducted using data from a prospectively maintained institutional database on all consecutive patients with breast cancer undergoing surgery between January 2016 and March 2021 at Dana-Farber Brigham Cancer Center. The study included 5235 patients with stage I through III, ERBB2-negative invasive breast cancer. Tumors were classified as ERBB2-low if they had an ERBB2 immunohistochemical (IHC) score of 1+ or 2+ with negative in situ hybridization assay and ERBB2-0 if they had an ERBB2 IHC score of 0. Data were analyzed from September 2021 through January 2022. Standard treatment according to institutional guidelines. Comparison of clinicopathologic characteristics and disease outcomes (pathologic complete response rate [pCR], disease-free survival, distant disease-free survival, and overall survival) between patients with ERBB2-low and ERBB2-0 breast cancer. Among 5235 patients with ERBB2-negative invasive breast cancer (5191 [99.2%] women; median [range] age at primary surgery, 59.0 [21.0-95.0] years), 2917 patients (55.7%) and 2318 patients (44.3%) had ERBB2-low and ERBB2-0 tumors, respectively. Expression of HR was significantly more common among ERBB2-low compared with ERBB2-0 tumors (2643 patients [90.6%] vs 1895 patients [81.8%]; P < .001). The rate of ERBB2-low tumors increased progressively, from 296 of 739 estrogen receptor (ER)-negative tumors (40.1%) to 31 of 67 ER-low (ie, ER 1%-9%) tumors (46.3%), 37 of 67 ER-moderate (ie, ER, 10%-49%) tumors (55.2%), 2047 of 3542 ER-high (ie, ER, 50%-95%) tumors (57.8%), and 499 of 803 ER-very high (ie, ER > 95%) tumors (62.1%) (P < .001). Among 675 patients receiving neoadjuvant chemotherapy, those with ERBB2-0 tumors experienced higher pCR rates (95 patients [26.8%] vs 53 patients [16.6%]; P = .002). However, there were no statistically significant differences in pCR rate between ERBB2-low and ERBB2-0 tumors when separately analyzing HR-positive, ER-low, HR-positive without ER-low, or TNBC tumors. In exploratory survival analysis, no differences by ERBB2-low expression in disease-free survival, distant disease-free survival, or overall survival were observed among patients with HR-positive tumors or TNBC. The results of this cohort study did not support the interpretation of ERBB2-low breast cancer as a distinct biologic subtype. ERBB2-low expression was positively associated with level of ER expression, and ER-low tumors were enriched among ERBB2-0 tumors, suggesting that, given the worse prognosis of ER-low tumors, they may be associated with confounding of prognostic analyses of ERBB2-low expression.

Dynamic Contrast-enhanced Magnetic Resonance Imaging Evaluation of Whole Tumour Perfusion Heterogeneity Predicts Distant Disease-free Survival in Locally Advanced Rectal Cancer

AimsTo evaluate diffusion-weighted imaging and dynamic contrast-enhanced magnetic resonance imaging for the prediction of disease-free survival (DFS) in patients with locally advanced rectal cancer. Materials and methodsPatients with stage II or III rectal adenocarcinoma undergoing neoadjuvant chemoradiotherapy (CRT) and surgery were eligible. Patients underwent multi-parametric magnetic resonance imaging (diffusion-weighted imaging and dynamic contrast-enhanced) before CRT, during CRT (week 3) and after CRT (1 week prior to surgery). Whole tumour apparent diffusion coefficient (ADC) and Ktrans histogram quantiles (10th, 25th, 50th, 75th, 90th) were extracted for analysis. The associations between ADC and Ktrans at three timepoints with time to relapse were analysed as a continuous variable using a Cox proportional hazard model. ResultsThirty-three patients were included in this analysis. The median follow-up was 4.4 years. No patient had locoregional relapse. Nine patients developed distant metastases. The hazard ratios for after CRT Ktrans 10th (P = 0.035), 25th (P = 0.048), 50th (P = 0.046) and 75th (P = 0.045) quantiles were statistically significant for DFS. The best Ktrans cut-off point after CRT for predicting relapse was 28 × 10−3 mL/g/min (10th quantile), with a higher Ktrans value predicting distant relapse. The 4-year DFS probability was 0.93 for patients with after CRT Ktrans value ≤28 × 10−3 mL/g/min versus 0.45 for patients with after CRT Ktrans value >28 × 10−3 mL/g/min. ADC was not able to predict DFS. ConclusionsPatients with higher Ktrans values after CRT (before surgery) in a histogram analysis of whole tumour heterogeneity had a significantly lower 4-year distant DFS and could be considered for more intense systemic therapy.

Risk-Stratified Intraoperative Radiation Therapy as a Definitive Adjuvant Radiation Therapy Modality for Women With Early Breast Cancer

Radiation therapy is an integral component of adjuvant therapy in women who undergo breast conservative surgery, decreasing the likelihood of tumor recurrence and extending survival. The likelihood of tumor recurrence is highest within a proximity of the lumpectomy cavity, which prompted the idea of partial breast irradiation in place of the usual standard-of-care treatment with external beam whole breast radiation therapy. Targeted intraoperative radiation therapy (TARGIT-A) is a multicenter trial initially developed in 1999 and designed as a randomized clinical trial comparing whole breast radiation therapy to risk-adapted intraoperative radiation therapy (IORT). TARGIT-A recruited its first patient in March 2000, with the study concluding in 2012. At a median follow-up of 8.6 years, the prepathology TARGIT-A trial noted results to be noninferior to external beam radiation therapy, with no statistically significant difference in ipsilateral breast tumor recurrence, mastectomy-free survival, distant disease-free survival, or breast cancer–specific mortality. These results are consistent with the majority of retrospective and prospective trials. Risk-adapted IORT, as performed in the prospective randomized TARGIT-A trial, gives level 1 evidence that this approach is a standard option in the treatment of breast cancer.