Five-year Distant Metastasis-free Survival Research Articles

Prognosis of locoregional recurrence after early breast cancer with immediate breast reconstruction.

e12595 Background: Several studies have shown no difference in the prognosis of breast cancer patients who underwent total mastectomy (MT) with or without immediate breast reconstruction (IBR), which is now a standard surgical technique in the treatment of breast cancer. While some studies have reported a poor prognosis for locoregional recurrence (LRR) following breast cancer surgery, the prognosis of LRR without simultaneous distant metastasis after IBR is not known. We conducted a multi-facility retrospective observational study to investigate the prognosis of breast cancer patients with LRR after IBR. Methods: Of the 4,726 primary breast cancer patients for whom IBR was performed at 12 Japanese medical facilities between January 1, 2008, and December 31, 2016, MT or skin-sparing mastectomy (SSM) was performed in 3,295 patients. LRR was observed in 87 of these patients, 17 of whom had distant metastasis (n=13) or metastasis to the supraclavicular or internal mammary lymph nodes (n=4) before LRR was excluded. The measured outcomes were IBR-LRR-related prognostic factors, five-year distant metastasis-free survival (DMFS), and five-year overall survival (OS). The statistical analyses employed Kaplan–Meier curves and a Cox proportional hazards model. Results: The median observation period was 39.3 months and the median age at which IBR was performed was 44 years. There were 61 cases (87.1%) of invasive cancer. Sixty-one cases (87.1%) were ER-positive, 54 (77.1%) were PR-positive, and 13 (19.7%) were HER2-positive. Fifteen cases (21.4%) had pathological lymph node metastasis (pN), 60 cases (85.7%) underwent implant reconstruction, 33 cases (47.1%) had a disease-free interval ≤ 36 months, 9 cases (12.9%) had regional lymph node recurrence (RR), and 65 cases (92.9%) underwent surgical resection to treat LRR. The five-year DMFS after LRR was 92.4%, and the five-year OS was 91.2%. The relationship between DMFS and clinical pathology factors was analyzed using a Cox proportional hazards model. Univariate analysis revealed significant differences for pN (HR 10.634, 95% CI 1.102–102.616, P=0.041) and RR (HR 9.960, 95% CI 1.400–70.862, P=0.022), and multivariate analysis indicated that RR was the only independent prognostic factor for DMFS (HR 7.834, 95% CI 1.085–56.587, P=0.041) (Table 1). Univariate analysis revealed significant differences for post-mastectomy radiation therapy (PMRT) (HR 130.676, 95% CI 1.552–412.278, P=0.023) and RR (HR 8.181, 95% CI 1.106–60.503, P=0.043), and multivariate analysis indicated that both PMRT (HR 61.281, 95% CI 2.540–1478.426, P=0.010) and RR (HR 15.687, 95% CI 1.354–181.772, P=0.028) were independent prognostic factors for OS. Conclusions: This is the first study to report the prognosis of breast cancer patients with LRR after IBR. Although these patients have a favorable prognosis overall, our results indicate that RR may be a significant factor for poor prognosis.

Is therapeutic lymph node dissection of value for lymph node recurrence in melanoma?

BackgroundTherapeutic lymphadenectomy (TLND) is still performed in most melanoma patients to treat nodal recurrences after initial negative lymph node biopsy (-SLNB), despite the lack of evidence for survival benefit. We sought to compare melanoma-specific survival (MSS) and distant metastasis-free survival (DMFS) of patients who underwent TLND versus no TLND using our institutional and MSTL-1 databases. MethodsWe identified 146 patients with nodal recurrence following -SLNB: 132 underwent TLND and 14 did not. DMFS and MSS were evaluated for the cohorts followed by a matched-pair analysis between the cohorts. ResultsNo difference was observed in five-year DMFS (p ​= ​0.454) and five-year MSS (p ​= ​0.945) between the two groups. The matched-pair analysis showed similar results (p ​= ​0.329 and p ​= ​0.363 for DMSF and MSS, respectively). ConclusionsFrom this limited retrospective study, TLND for nodal recurrence after a -SLNB does not appear to improve DMFS or MSS in melanoma patients compared to no TLND.

Age-Independent Preoperative Chemosensitivity and 5-Year Outcome Determined by Combined 70- and 80-Gene Signature in a Prospective Trial in Early-Stage Breast Cancer

BackgroundThe Neoadjuvant Breast Symphony Trial (NBRST) demonstrated the 70-gene risk of distant recurrence signature, MammaPrint, and the 80-gene molecular subtyping signature, BluePrint, precisely determined preoperative pathological complete response (pCR) in breast cancer patients. We report 5-year follow-up results in addition to an exploratory analysis by age and menopausal status.MethodsThe observational, prospective NBRST (NCT01479101) included 954 early-stage breast cancer patients aged 18–90 years who received neoadjuvant chemotherapy and had clinical and genomic data available. Chemosensitivity and 5-year distant metastasis-free survival (DMFS) and overall survival (OS) were assessed. In a post hoc subanalysis, results were stratified by age (≤ 50 vs. > 50 years) and menopausal status in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2−) tumors.ResultsMammaPrint and BluePrint further classified 23% of tumors to a different subtype compared with immunohistochemistry, with more precise correspondence to pCR rates. Five-year DMFS and OS were highest in MammaPrint Low Risk, Luminal A-type and HER2-type tumors, and lowest in MammaPrint High Risk, Luminal B-type and Basal-type tumors. There was no significant difference in chemosensitivity between younger and older patients with Low-Risk (2.2% vs. 3.8%; p = 0.64) or High-Risk tumors (14.5% vs. 11.5%; p = 0.42), or within each BluePrint subtype; this was similar when stratifying by menopausal status. The 5-year outcomes were comparable by age or menopausal status for each molecular subtype.ConclusionIntrinsic preoperative chemosensitivity and long-term outcomes were precisely determined by BluePrint and MammaPrint regardless of patient age, supporting the utility of these assays to inform treatment and surgical decisions in early-stage breast cancer.

Propensity Score Matched Study of Tri-Weekly vs. Weekly Platinum-Based Chemotherapy Concurrent with Radiotherapy in the Treatment of Locally Advanced Cervical Cancer

Objective: To compare tumor control and toxicity between tri-weekly chemotherapy and weekly platinum-based chemotherapy in locally advanced cervical cancer using the propensity score matching method.Material and Methods: DESIGN: Retrospective cohort with propensity score matched population. SETTING: Four university hospitals. PARTICIPANTS: 781 advanced local cervical cancer patients. INTERVENTION: tri-weekly platinum-based chemoradiotherapy versus weekly chemoradiotherapy OUTCOMES: Overall survival (OS), local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), distant metastasis-free survival (DMFS), and toxicity, including hematological and renal toxicity.Results: Overall median follow-up time was 59.5 months. After the propensity score matching process was completed, 326 patients were analyzed (163 in each group). The five-year OS was 66% and 64% (p 0.630); five-year LRFS was 85% and 81% (p 0.209); five-year RRFS was 89% and 94% (p 0.307); and five-year DMFS was 75% and 79% (p 0.420) in the tri-weekly and weekly groups, respectively. The patients in the tri-weekly and the weekly group had grade 2-3 neutropenia (10.5% vs 2.5%). The other toxicities appeared to be similar in both groups in terms of white blood count, platelet and creatinine.Conclusion: There was a potential small benefit of local control (4%) and overall survival (2%) with the tri-weekly regimen but we could not demonstrate statistical significance. However, this came at the price of an increase of 7% to 8% in grade 2-3 neutropenia.

Interstitial multicatheter HDR-brachytherapy as accelerated partial breast irradiation after second breast-conserving surgery for locally recurrent breast cancer.

ABSTRACTOur aim was to evaluate the efficacy and toxicity of interstitial multicatheter high dose rate brachytherapy (imHDR-BRT) as accelerated partial breast irradiation (APBI) after second breast-conserving surgery (BCS) in patients with ipsilateral breast tumor recurrence (IBTR). Between January 2010 and December 2019, 20 patients with IBTR who refused salvage mastectomy (sMT) were treated with second BCS and post-operative imHDR-BRT as APBI. All patients had undergone primary BCS followed by adjuvant external beam radiotherapy. Median imHDR-BRT dose was 32 Gy delivered in twice-daily fractions of 4 Gy. Five-year IBTR-free survival, distant metastasis-free survival (DMFS), overall survival (OS) as well as toxicity and cosmesis were evaluated in the present retrospective analysis. Median age at recurrence and median time from the first diagnosis to IBTR was 65.1 years and 12.2 years, respectively. After a median follow-up of 69.9 months, two patients developed a second local recurrence resulting in 5-year IBTR free-survival of 86.8%. Five-year DMFS and 5-year OS were 84.6% and 92.3%, respectively. Grade 1–2 fibrosis was noted in 60% of the patients with no grade 3 or higher toxicity. Two (10%) cases of asymptomatic fat necrosis were documented. Cosmetic outcome was classified as excellent in 6 (37.5%), good in 6 (37.5%), fair in 3 (18.75%) and poor in 1 (6.25%) patient, respectively. We conclude that imHDR-BRT as APBI re-irradiation is effective and safe for IBTR and should be considered in appropriately selected patients.

Correlation between nasopharyngeal carcinoma tumor volume and the 2002 International Union Against Cancer tumor classification system

BackgroundThe correlation between primary tumor volume and nasopharyngeal carcinoma (NPC) UICC 2002 T classification, N classification and distant metastasis after radiation therapy was discussed to provide further evidence for the inclusion of tumor volume into the TNM classification staging system.MethodsBetween February 2001 and December 2008, 666 patients with NPC treated with intensity-modulated radiation therapy (IMRT) were analyzed retrospectively. Primary gross tumor volume was calculated from treatment planning computed tomography scans. The Kruskal-Wallis and Mann–Whitney tests were used for comparison of continuous variables and the chi-square test was used for categorical variables. A logistic regression model was used for multivariate analysis.ResultsMedian primary tumor volume of the 666 patients was 20.35 ml (range, 0.44 − 192.63 ml), and it gradually increased with T classification. Statistically significant differences in tumor volume were observed between patients with different T classifications (p < 0.001). The cervical lymph node metastasis rate was 64.7% (430/666); the differences in primary tumor volume between patients with or without lymph node metastasis were statistically significant (p < 0.001). Posttreatment distant metastasis occurred in 100 NPC patients, and the five-year distant metastasis-free survival was 84.2%. Univariate and multivariate analyses showed that N classification (p < 0.001) and tumor volume (p = 0.007) were the main factors influencing distant metastasis.ConclusionTumor volume was correlated with T classification, cervical lymph node mestastasis and distant metastasis after radiation therapy in nasopharyngeal carcinoma, suggesting that tumor volume should be included into the TNM staging system.

Development and validation of a robust prognostic and predictive signature for colorectal cancer (CRC) patients

4036 Background: Between 25 and 35% of stage II CRC patients will experience a recurrence of their disease and may benefit from adjuvant chemotherapy. Official guidelines give suggestions but no clear recommendation for best risk stratification. Here we describe the development a robust signature that predicts disease relapse and can assist in treatment decisions. Methods: Fresh frozen tumor tissues from 180 patients with stage I, II and III colorectal cancer undergoing surgery were analyzed using high density Agilent 44K oligonucleotide arrays. Median FU was 70.2 months; 85% of patients did not receive adjuvant chemotherapy. Unsupervised hierarchical clustering based on full-genome gene expression measurement indicated the existence of 3 main colon molecular subclasses. Survival analysis of the 3 classes showed that subtype C (n= 27) had a poor outcome and subtype A (n= 48) good outcome. Only the intermediate group B (n=104) was used to develop a signature by using a cross validation procedure to score all genes for their association with 5-yr distant metastasis free survival (DMFS) and subsequently applied to all samples (n=180). The obtained gene signature was further validated on an independent cohort of 178 stage II + III colon samples. Results: A set of 38 prognosis related gene probes showed robust DMFS association in over 50% of all iterations in the Training Set of 180 samples. The gene signature was validated on an independent cohort of 178 samples from stage II + III colon cancer patients. The profile classified 61% of the validation samples as low-risk and 39% as high-risk. The low- and high-risk samples showed a significant difference in DMFS with a HR of 3.19 (P= 8.5e-4). Five-year DMFS rates were 89% (95%CI 83–95) for low-risk and 62% (95%CI 50–77) for high-risk samples. Moreover, the profile showed a significant performance within stage II (P=0.0058) and III (P=0.036) only samples. The performance of the profile was significant for both untreated (P=0.0082) and treated patients (P=0.016) suggesting that its power is independent of treatment benefits. Conclusions: ColoPrint is able to predict the prognosis of stage II and III colon cancer patients and facilitates the identification of patients who would benefit from adjuvant chemotherapy. [Table: see text]

Radioterapia externa conformada 3D para o carcinoma de próstata: experiência do Instituto do Radium de Campinas com 285 pacientes

OBJETIVO: Reportar resultados de tratamentos do câncer de próstata com radioterapia conformada 3D realizados em uma única instituição. MATERIAIS E MÉTODOS: De julho de 1997 a janeiro de 2002, 285 pacientes consecutivos com câncer de próstata foram submetidos a radioterapia conformada 3D com dose mediana de 7.920 cGy na próstata e analisados retrospectivamente. A distribuição segundo o grupo de risco foi a seguinte: baixo risco - 95 (33,7%); risco intermediário - 66 (23,4%); alto risco - 121 (42,9%) pacientes. RESULTADOS: Em seguimento mediano de 53,6 meses (3,6-95,3 meses), sobrevidas atuariais global, causa específica, livre de metástases a distância e livre de recidiva bioquímica em cinco anos foram de 85,1%, 97,0%, 94,2% e 75,8%, respectivamente. Sobrevidas atuariais livre de toxicidade retal e urinária tardias em cinco anos foram de 96,4% e 91,1%, respectivamente. Ressecção transuretral pré-radioterapia conformada 3D e doses &gt; 70 Gy em 30% do volume da bexiga implicaram maior toxicidade urinária tardia grau 2-3 em cinco anos (p = 0,0002 e p = 0,0264, respectivamente). CONCLUSÃO: A primeira experiência relatada de radioterapia conformada 3D no Brasil permitiu altas doses de radiação, com toxicidades retal e urinária aceitáveis. A existência de ressecção transuretral de próstata pré-radioterapia conformada 3D pode sinalizar maior risco de toxicidade urinária tardia grau 2-3 após irradiação. Restrição da dose &lt; 70 Gy em 30% do volume da bexiga à tomografia de planejamento pode reduzir complicações urinárias tardias.

Long-term efficacy of preoperative radiotherapy for locally advanced low rectal cancer

The purpose of this study was to assess the long-term efficacy of preoperative radiotherapy for locally advanced low rectal cancer. Between April 1990 and June 2005, all patients who underwent surgery for low rectal cancer with a pretreatment diagnosis of T3 or resectable T4 without distant metastasis were enrolled. The total dose of radiation was 45 Gy. Patients with a partial or complete response were defined as radiotherapy responders (RT-R) and the others as radiotherapy non-responders (RT-NR). Patients who did not receive radiotherapy were termed the non-radiotherapy group (NRT). The endpoint of this study was overall survival and local and/or distant metastasis. There were 24 patients in RT-R, 26 in RT-NR, and 40 in NRT. Gastrointestinal complications were commonly observed in all groups. RT-R had a significantly higher incidence of genitourinary complications. Five-year overall survival rate was 79.6% in RT-R, 58.9% in RT-NR, and 58.8% in NRT. The difference was significant in favor of RT-R over the others (P=0.015, 0.024, respectively). Five-year local recurrence-free survival rate was 100% in RT-R, 81.5% in RT-NR, and 74.9% in NRT. RT-R had significantly improved local control compared with the others (P=0.034, 0.021, respectively). Five-year distant metastasis-free survival was not statistically different among all groups. Survival benefit of preoperative radiotherapy was limited to responders. Considering the increased risk of adverse effects, identification of predictors of radiosensitivity is required in order to provide the most suitable treatment for individual patients.