Adjuvant Systemic Therapy Research Articles

Multi-task Bayesian model combining FDG-PET/CT imaging and clinical data for interpretable high-grade prostate cancer prognosis.

We propose a fully automatic multi-task Bayesian model, named Bayesian Sequential Network(BSN), for predicting high-grade(Gleason 8) prostate cancer(PCa) prognosis using pre-prostatectomy FDG-PET/CT images and clinical data. BSN performs one classification task and five survival tasks: predicting lymph node invasion (LNI), biochemical recurrence-free survival (BCR-FS), metastasis-free survival, definitive androgen deprivation therapy-free survival, castration-resistant PCa-free survival, and PCa-specific survival(PCSS). Experiments are conducted using a dataset of 295patients. BSN outperforms widely used nomograms on all tasks except PCSS, leveraging multi-task learning and imaging data. BSN also provides automated prostate segmentation, uncertainty quantification, personalized feature-based explanations, and introduces dynamic predictions, a novel approach that relies on short-term outcomes to refine long-term prognosis. Overall, BSN shows great promise in its ability to exploit imaging and clinicopathological data to predict poor outcome patients that need treatment intensification with loco-regional or systemic adjuvant therapy for high-risk PCa.

ASO Author Reflections: Survival Benefit of Adjuvant Systemic Therapy After Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma.

ASO Author Reflections: Survival Benefit of Adjuvant Systemic Therapy After Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma.

Prognostic Significance of Angiogenesis in invasive ductal carcinoma

Background: Angiogenesis is essential for tumor growth and metastasis. Axillary lymphnode status has been the most important prognostic factor in operable breast carcinoma, but it does not fully account for the varied disease outcome. More accurate prognostic indicators would help in selection of patients at high risk for disease recurrence and death who are candidates for systemic adjuvant therapy. Microvessel density in invasive ductal carcinoma (measures of tumor angiogenesis) is associated with metastasis and thus may be a prognostic indicator. Objective: To correlate intratumoral and peritumoral angiogenic microvessel density with lymphnode metastasis in invasive ductal carcinoma. Material and Methods: It is a cross sectional observational study, carried out at the department of Pathology, BSMMU from January 2016 to December 2017. A total 48 mastectomy samples with axillary nodes from histologically confirmed invasive ductal carcinoma were included in this study. Weidner method was used for calculating micro vessels density. Sections examined to evaluate the density of angiogenic vessels by immuohistological stain with vWF expression in invasive breast cancer. Correlation between angiogenic vessels density with or without lymphnode metastasis was taken. Results: In this study angiogenic vessel count is more in the intratumoral area than peritumoural area. There was a positive significant correlation between lymphnode metastasis with micro vessel density in both peritumoral and intratumoral areas in Weidner method in vWF stain. J Shaheed Suhrawardy Med Coll 2023; 15(1): 59-65

Real-world perioperative treatment patterns and burden of recurrent disease in patients with high-risk endometrial cancer: a SEER-Medicare study

Objectives To elucidate unmet needs in high-risk endometrial cancer (EC), this study described perioperative treatment patterns in Medicare beneficiaries with high-risk EC and quantified the impact of disease recurrence on clinical and economic outcomes among patients receiving adjuvant therapy. Methods Patients aged ≥66 years with high-risk EC (stage I/II EC of non-endometrioid histology or stage III/IVA EC of any histology) receiving hysterectomy with bilateral salpingo-oophorectomy from SEER-Medicare data (2007–2019) were identified; perioperative treatment patterns were described. Post-operative treatment patterns were described among patients receiving adjuvant therapy; overall survival (OS), all-cause and EC-related healthcare resource utilization and costs were evaluated from recurrence date (using a claims-based algorithm developed with clinical input) for recurrent patients and from a frequency-matched date for non-recurrent patients. Results Of 2,279 patients receiving EC surgery, 3.1% received neoadjuvant therapy and 55.3% received adjuvant therapy. Among 1,199 patients receiving adjuvant therapy, systemic adjuvant therapy with radiation (38.9%) was most common. Median OS was 1.4 years among 378 (31.5%) recurrent patients identified over a median follow-up of 3.7 years. Recurrent patients had significantly higher per-patient-year rates of all-cause outpatient visits (37.7 vs. 22.6), EC-related outpatient visits (14.5 vs. 3.0), and all-cause hospitalizations (1.3 vs. 0.4) than non-recurrent patients, and an excess of $84,562 and $62,128 in all-cause and EC-related annual costs, predominantly driven by hospitalizations. Conclusions Our findings highlight the considerable clinical and economic burden experienced by patients with high-risk EC experiencing recurrence and emphasize the unmet need for novel therapies in early settings to mitigate this burden.

Is pancreatic adenosquamous carcinoma (PASC) a surgical disease? A large healthcare system review

IntroductionPancreatic cancer represents an increasing cause of cancer-related deaths. Pancreatic adenosquamous carcinoma (PASC) is a rare subtype of pancreas cancer. Optimal treatment is not well-defined. This review aims to provide a detailed analysis of the natural history, management, and outcomes of the patients with PASC within a single large healthcare system. Materials and methodsA large healthcare database was used to retrospectively identify all patients with histological diagnosis of PASC from 2010 to 2020. The cohort was evaluated as a whole and according to the following management modalities: operative, non-metastatic non-operative, and patients with metastatic disease. Abstracted data included patient characteristics, oncologic characteristics at presentation, and details of surgical and non-surgical treatment. ResultsIn total, 60 patients with PASC were identified. All patients had confirmed histopathological diagnosis of PASC. Mean age at the time of diagnosis was 70.9 years, and 28 patients were male (46.7 %). Most patients presented with pancreas head tumors (60 %). Thirty-four patients presented with non-metastatic disease (56.6 %). The operative group consisted of 17 patients (28.3 %). Most patients received adjuvant systemic therapy (70.6 %). Majority of patients experienced recurrence (76.5 %), with median time to recurrence at 6.5 months. Median overall survival in the operative group was 19.1 months. Seventeen patients with non-metastatic disease (28.3 %) did not undergo resection. Median overall survival of this cohort was 3.3 months. Systemic chemotherapy was used in 8 patients. Approximately half of patients with non-metastatic disease (9/17) did not receive any treatment due to rapid physical deterioration or poor functional status at baseline. Median survival for the non-treatment group was 1.7 months. At presentation, 26 patients (43.3 %) had metastatic disease. Most common site of metastasis was the liver. Median survival for patients with metastatic disease was 3.1 months. DiscussionPASC is a distinct entity from glandular PDAC, and it appears to be a more aggressive disease process. Complete resection confers survival benefit but is not curative. Furthermore, few patients undergo surgery, even with seemingly resectable disease. Systemic therapy administration is limited in many patients due to physiologic decline. Dismal clinical course and poor survival is universal among all patients who do not undergo any treatment modality, regardless of metastatic status. Globally grim prognosis appears to be due early systemic effects, disease progression and lack of effective systemic therapy. ConclusionsPASC remains a poorly understood cancer and portends particularly poor prognosis. It is associated with a rapid clinical decline, poor response to systemic therapy, early recurrence, and poor overall survival. However, ability to treat with surgery and chemotherapy may best prolong survival. SynopsisPancreatic adenosquamous carcinoma (PASC) is a rare subtype of pancreatic cancer. In this study, we evaluated 60 patients with PASC. PASC is a systemic disease characterized by rapid clinical decline, poor response to systemic therapy, early recurrence, and poor survival. Despite resection or systemic therapy, patients succumb rapidly.

Real World Evidence Study to Assess Incidence, Treatment Patterns, Clinical Outcomes, and Health Care Resource Utilization in Early-Stage, High-Risk HER2-Negative Breast Cancer in Alberta, Canada

BackgroundData are needed to improve the current understanding of the epidemiology of patients with high-risk, HER2-negative, early breast cancer (eBC) (hormone receptor positive [HR+]/HER2-negative BC and triple-negative BC [TNBC]). Patients and MethodsThis retrospective longitudinal cohort study used real-world, population-level data that included all individuals newly diagnosed with high-risk, HER2-negative eBC in Alberta, Canada, between 2010 and 2019. Data on treatment, laboratory results and pathology findings were collected through electronic health records and administrative databases. ResultsThe annual cumulative incidence of high-risk, HER2-negative eBC ranged from 6% to 9% of all incident BC cases. Individuals with TNBC were more likely to be younger, had stage II disease, grade 3 histology and received systemic therapy at a community centre (P < .05) compared to individuals with HR+/HER2-negative eBC. Only 14% of individuals diagnosed in 2010-2017 underwent germline BRCA testing postdiagnosis. Neoadjuvant systemic therapy was given to 37% of individuals. Adjuvant systemic therapy use increased from 77% (2012-2015) to 84% (2019). The 5-year overall survival (OS) from initiation of adjuvant systemic therapy or date of surgery (for individuals who did not receive adjuvant systemic therapy) was 77% (95% CI: 75-79). OS was significantly worse among individuals who were older, had grade 3 histology, had stage III disease, or had nodal involvement (P < .05). OS among individuals with TNBC between 2016 and 2019 who initiated adjuvant capecitabine was markedly worse compared to the overall cohort (2-year OS: 70% vs. 89%). ConclusionOutcomes analyses in this high-risk, HER2-negative eBC population suggest a continued unmet clinical need.

Prioritizing Radiation and Targeted Systemic Therapies in Patients with Resected Brain Metastases from Lung Cancer Primaries with Targetable Mutations: A Report from a Multi-Site Single Institution.

Background/Objectives: Brain metastases (BrMs) are a common complication of non-small cell lung cancer (NSCLC), present in up to 50% of patients. While the treatment of BrMs requires a multidisciplinary approach with surgery, radiotherapy (RT), and systemic therapy, the advances in molecular sequencing have improved outcomes in patients with targetable mutations. With a push towards the molecular characterization of cancers, we evaluated the outcomes by treatment modality at our institution with respect to prioritizing RT and targeted therapies. Methods: We identified the patients with NSCLC BrMs treated with surgical resection. The primary endpoints were in-brain freedom from progression (FFP) and overall survival (OS). The secondary endpoint included index lesion recurrence. The tumor molecular profiles were reviewed. The outcomes were evaluated by treatment modality: surgery followed by adjuvant RT and/or adjuvant systemic therapy. Results: In total, 155/272 (57%) patients who received adjuvant therapy with adequate follow-up were included in this analysis. The patients treated with combination therapy vs. monotherapy had a median FFP time of 10.72 months vs. 5.38 months, respectively (p = 0.072). The patients of Hispanic/Latino vs. non-Hispanic/Latino descent had a statistically significant worse OS of 12.75 months vs. 53.15 months, respectively (p = 0.015). The patients who received multimodality therapy had a trend towards a reduction in index lesion recurrences (χ2 test, p = 0.063) with a statistically significant improvement in the patients receiving immunotherapy (χ2 test, p = 0.0018). Conclusions: We found that systemic therapy combined with RT may have an increasing role in delaying the time to progression; however, there was no statistically significant relationship between OS and treatment modality.

Análisis multicéntrico del manejo quirúrgico y tratamiento adyuvante de los pacientes con melanoma y positividad en la biopsia selectiva del ganglio centinela

ObjectivesTo determine the evolution of the indication for CLND in patients with a positive SLNB, as well as the characteristics associated with its performance. Material and methodsWe conducted a multicenter retrospective observational study with patients with skin melanoma and positive sentinel lymph nodes diagnosed from 2017 through 2022 at 8 Spanish centers and 1 Italian center. ResultsA total of 430 patients were included, 54% men, with 358 (75.1%) aged between 45 and 80 years. A total of 133 cases (31%) exhibited Breslow thickness > 4mm, 206 cases (49.1%) were ulcerated, and in 213 cases (55.7%), lymph node metastasis was > 1mm. Isolated lymphadenectomy or followed by adjuvant therapy was performed in 146 patients (34.1%). After multivariate logistic regression, the factors associated with the performance of CLND were Breslow > 4mm, the acral lentiginous melanoma histological subtype, lymph node metastasis size > 1mm, extracapsular spread, and the participant hospital. Age > 80 years was inversely associated. ConclusionWhile the frequency of CLND in patients with melanoma and positive SLNB has decreased, the indication for systemic adjuvant therapy in these patients has increased. However, CLND is still indicated in patients with high-risk characteristics.

Systemic chemotherapy in addition to CRS-HIPEC for colorectal peritoneal metastases: A critical systematic review on the impact on overall survival.

In patients with resectable colorectal peritoneal metastases, it is unclear whether systemic chemotherapy, in addition to cytoreductive surgery-hyperthermic intraperitoneal chemotherapy(CRS-HIPEC), improves overall survival (OS). This systematic review of 12 retrospective studies involving 3721 patients aimed to summarize the available evidence. Contradictory results were found regarding the effectiveness of neoadjuvant, adjuvant, and perioperative systemic therapies on OS, with a high risk of bias. Available evidence remains inconclusive, stressing the need for prospective, randomized trials, like the ongoing Dutch CAIRO6-trial.

The impact of systemic and topical antimicrobial therapy combined with non-surgical periodontal therapy: A meta-analysis.

Combining antibiotics with non-surgical periodontal therapy has a beneficial impact in case of infection while its role for dental-related outcomes is still unclear. The current study's main objective was to evaluate the impact of adding adjuvant systemic and topical antimicrobial therapy to non-surgical periodontal therapy. A systematic literature search was accomplished and 1,093 study participants with periodontal diseases were recruited to the current study; 541 of them were treated with adjuvant systemic or topical antimicrobial agents and 552 with non-surgical interventions. The inclusion criteria of the current study took into account only randomized clinical trials. Adding systemic antibiotics to non-surgical intervention resulted in a significant enhancement regarding probing pocket depth reduction (PPD). Metronidazole/amoxicillin showed a significant impact on PPD and the clinical attachment level (CAL), while doxycycline showed no significant impact regarding CAL. Using topical antimicrobial agents showed a significant beneficial role in reducing PPD regarding doxycycline, while non-significant effects were seen with metronidazole. Adding adjuvant systemic and topical antimicrobial agents to non-surgical periodontal therapy showed a beneficial impact regarding PPD and CAL (metronidazole/amoxicillin and doxycycline). In addition, using doxycycline as a topical agent showed a beneficial impact on the reduction of PPD.

Presenting decision-relevant numerical information to Dutch women aged 50-70 with varying levels of health literacy: Case example of adjuvant systemic therapy for breast cancer.

If communicated adequately, numerical decision-relevant information can support informed and shared decision making. Visual formats are recommended, but which format supports patients depending on their health literacy (HL) levels for specific decisions is unclear. The aim of this study is to investigate: 1) the effect of survival rates and side-effects presentation formats on comprehension and 'feeling informed'; 2) differential effects among women with higher/lower HL, with adjuvant systemic breast cancer therapy as case example. Two online experiments among women from the Dutch population without a history of breast cancer were conducted. Experiment 1 had a 3 (survival rate format: text block-bar graph-icon array) x 2 (HL: low-high) between-subjects design. Experiment 2 had a 5 (side-effects format: no probability information-probability information in numbers with or without a visualisation-probability information in numbers with or without a visualisation accompanied by a description of the side-effects) x 2 (HL: low-high) design. Primary outcomes were comprehension and feeling informed (Experiment 2 only). Formats were previously designed in co-creation with patients. In Experiment 1, presentation format did not affect gist or verbatim comprehension. Higher HL was associated with higher gist comprehension. Experiment 2 showed an interaction between presentation format and HL on 'feeling informed'. When provided with visualised probability information without a description of the side-effects, women with lower HL felt better informed than women with higher HL. Visual formats did not enhance comprehension of survival rate information beyond a well-designed text block format. However, none of the formats could overcome HL differences. When designing decision-relevant information, visualisations might not necessarily provide an advantage over structured numerical information for both patients with lower and higher HL. However, a deeper understanding of presenting side-effect information is warranted.

Disparities in postoperative adjuvant therapy utilization and factors impacting survival among anaplastic thyroid cancer patients

BackgroundAnaplastic thyroid cancer (ATC) is highly aggressive with a poor prognosis. Adjuvant systemic therapy and radiation post-surgery are endorsed by NCCN and ATA guidelines. Our study aimed to identify those at risk of forgoing postoperative adjuvant treatment and to determine survival predictors. MethodsWe used the National Cancer Database (NCDB) to identify ATC patients who underwent upfront thyroidectomy from 2010 to 2017, excluding those opting for palliative care. We compared demographics, characteristics, treatments, and outcomes between those who received adjuvant therapy and those who did not. Predictors of receiving adjuvant therapy were identified using logistic regression, while Cox regression identified survival factors. ResultsOf 563 patients, 160 received no adjuvant treatment, 82 received radiation only, 16 received systemic therapy only, and 305 received combination therapy. Notably, over 75 ​% of patients who did not receive adjuvant treatment had it excluded from their treatment plan, not due to refusal. Older age (OR 0.92) and non-white race/ethnicity (OR 0.33) were significant predictors of not receiving adjuvant therapy. Undergoing a total thyroidectomy, an R0 or R1 resection, and radiation or combination therapy were associated with better survival, while non-metropolitan location, primary tumor size >7.5 ​cm, and stage IVC disease were negative factors. ConclusionTotal thyroidectomy, R0/R1 resection, and adjuvant therapy reduce mortality in ATC patients. However, older patients and minorities are less likely to receive adjuvant therapy, underscoring disparities in treatment adherence.

Commission on Cancer Standards for Lymph Node Sampling and Oncologic Outcomes After Lung Resection

BackgroundThe newest Commission on Cancer standards recommend sampling 3 mediastinal and 1 hilar lymph node stations, 3 (N2) 1 (N1), for lung cancer resections. However, the relationship between the Commission on Cancer standards and outcomes has not been thoroughly investigated. MethodsA prospective institutional database was queried for clinical stage I-III lung resections before the implementation of the new standards. The relationship between the 3 (N2) 1 (N1) standard (“guideline concordant”) and outcomes (upstaging, complications, receipt of adjuvant therapy, locoregional/distant recurrence, and survival) was assessed with multivariable models and stratified by stage. ResultsOf 9289 pulmonary resections, 3048 (33%) were guideline concordant and 6241 (67%) were not. Compared with nonconcordant, those that were guideline concordant had higher rates of nodal upstaging (21% vs 13%; odds ratio [OR], 1.32 [95% CI, 1.14-1.51]; P < .001) and in-hospital complications (34% vs 27%; OR, 1.17 [95% CI, 1.05-1.30]; P = .004) but similar adjuvant systemic therapy administration (19% vs 13%; OR, 1.09 [95% CI, 0.95-1.24]; P = .2; 98% chemotherapy). Locoregional and distant recurrences were not significantly improved with guideline concordance across clinical stage I, II, and III subsets. Overall survival was similar in clinical stages I and II, but improved survival was observed for guideline concordant clinical stage III patients (hazard ratio, 0.85 [95% CI, 0.74-0.97]; P = .02). ConclusionsSampling 3 (N2) 1 (N1) was associated with increased upstaging and complications but not with decreased recurrence or mortality in clinical stage I or II patients. Survival was improved for concordant, clinical stage III patients. Further study is indicated to determine the ideal lymph node sampling strategy across heterogeneous lung cancer patients.

The Role of Medicaid Expansion on the Receipt of Adjuvant Chemotherapy in Patients With Lung Cancer

ObjectiveWe aimed to utilize a nationally representative database to study the effect of Medicaid expansion on the receipt of adjuvant chemotherapy in eligible patients. Materials and MethodsRetrospective review of the National Cancer Database (NCDB) was performed between 2006 and 2019. Patients with clinical T1-T3, N1, and M0 were included. Patients with nodal disease or tumors > 4 cm were eligible for adjuvant therapy. Demographic and clinical information were collected. A difference-in-difference analysis was performed to compare changes in the rate of adjuvant chemotherapy. ResultsTotal 9954 eligible patients were treated in states that expanded Medicaid coverage in January 2014 or later, with 4809 patients treated in the pre-expansion years (2012-2013) and 5145 patients treated in the postexpansion years (2017-2018). Following Medicaid expansion, eligible patients were more likely to receive adjuvant therapy (70.2% vs. 62.3%; P < .001). Compared with the pre-expansion period, patients who received adjuvant therapy were more likely to use Medicaid insurance postexpansion (7.8% vs. 5%, P < .001). Among patients using Medicaid coverage only, a greater percentage started adjuvant therapy within 8 weeks of resection following Medicaid expansion (46.6% vs. 38.3%, P = .048). The observed difference-in-difference in the change in adjuvant therapy rate from the pre-expansion period to the postexpansion period between expansion and nonexpansion states was 1.25% (95% Bootstrap CI −0.36% to −3.18%). There was a modest survival benefit in expansion states postexpansion. ConclusionMedicaid expansion appears to be associated with increased access to care, as shown by the increased receipt of adjuvant systemic therapy in eligible patients.

How deep is too deep? Assessing myometrial invasion as a predictor of distant recurrence in stage I endometrioid endometrial cancer

ObjectivesThe goal of this study was to evaluate the depth of myometrial invasion as a predictor of distant recurrence in patients with node-negative stage IB endometrioid endometrial cancer.MethodsA retrospective multicenter...

A case of BIA-ALCL in which postoperative chest wall recurrence was highly suspected: the third reported case of BIA-ALCL in Japan

BackgroundBreast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) is a rare malignancy. Many cases of BIA-ALCL are identified based on the presence of late-onset effusion and/or masses. Importantly, the United States Food and Drug Administration noted that in all cases diagnosed in patients with textured implants, the patients either had a history of mixed implantation of smooth and textured devices or no clinical history was supplied for review. In Japan, the first case of BIA-ALCL was reported in 2019, and we encountered the third case in Japan in December 2021. There have been a total of five cases of BIA-ALCL previously reported at Japanese academic conferences (Japan Oncoplastic Breast Surgery Society. http://jopbs.umin.jp/medical/index.html), of which only the first case has been published. Unlike the first case, this patient had clinical features that were highly suggestive of the postoperative chest wall recurrence of breast cancer, with a mass and rash on the skin.Case presentationThe patient was a 45-year-old woman who had undergone breast reconstruction after breast cancer surgery of the right breast 8 years previously. The patient presented with a mass and skin rash inside the inframammary area, and we suspected a damaged silicone breast implant (SBI) or chest wall recurrence. We examined the mass by a core needle biopsy and made a pathological diagnosis of BIA-ALCL. Imaging findings suggested internal thoracic lymph node swelling and lymphoma infiltration beyond the capsule but no metastatic lesions (cStage III). After en bloc resection of the SBI and lymphoma, adjuvant systemic therapy was performed.ConclusionWe encountered the third case of BIA-ALCL in Japan. This was a case with clinically advanced stage of disease; however, the BIA-ALCL was found to be in remission.

Radiation-Associated Angiosarcoma of the Breast: The State of the Art of a Rare and Aggressive Disease.

Considering the increasing number of conservative surgeries (quadrantectomies) for primary breast carcinoma, especially in the early stages, often followed by adjuvant radiotherapy, the incidence of radiation-associated angiosarcoma (RAS) is expected to rise in the coming decades, and it will represent a clinical and therapeutic challenge, as limited data are available due to the rarity and heterogeneity of the disease. Though the prognosis of these patients is poor, a number of clinical and pathological factors can be evaluated to better understand the course of RAS. The aim of this systematic review is to explore the available clinical-pathological, therapeutic, and prognostic data regarding RAS to evaluate its occurrence, diagnosis, treatment, and outcomes. RAS clinical data were identified by a systematic review conducted in five different databases (Medline, Web of Knowledge, Google Scholar, Scopus, and Cochrane). Only RAS works published in English, with access to the full manuscript text, and with clear results, were considered as eligible. We considered 52 papers comprising 319 RAS cases. The patient age at diagnosis ranged from 37 to 93 years, with most cases occurring from 5 to 10 years after breast irradiation. The most common clinical presentation was an aggressive development of macules, papules, or erythematous-violaceous skin discoloration at the site of previous radiation treatment for primary breast carcinoma. Complete surgical excision appeared to be the first-line treatment of the disease, in some cases followed by adjuvant local and/or systemic therapies. Despite different treatments, local recurrence rates ranged from 40% to 90%, leading to negative outcomes and poor prognosis for patients. Although the literature is limited and the data are heterogeneous and contentious, our review aims to highlight the importance of early diagnosis, multimodal treatment, and long-term follow-up of RAS in order to limit and prevent the aggressiveness of this neoplasm.

Evaluation of American Urological Association Renal Cell Carcinoma Risk Groups for Chromophobe Renal Cell Carcinoma

ObjectivesTo develop and compare various models for risk stratification in chromophobe renal cell carcinoma (chrRCC). Models have been developed to predict progression-free (PFS) and cancer-specific survival (CSS) following surgery for localized renal cell carcinoma (RCC). Notably, chromophobe RCC (chrRCC) is not included in American Urological Association (AUA) risk stratification, as nuclear grading is not recommended. MethodsWe queried our institutional registry to identify patients managed surgically for unilateral, sporadic, M0, chrRCC from 1970-2012. AUA risk groups were defined using reported criteria, excluding grade, and were compared to the Mayo system incorporating nodal involvement, perinephric/renal sinus fat invasion, and sarcomatoid differentiation. PFS and CSS were estimated using the Kaplan-Meier method. Predictive ability was summarized using c-indexes from Cox proportional hazard regression models. ResultsA total of 257 patients were identified. Thirty-nine patients experienced disease progression at a median 30 months (IQR 5.0-84) and 25 died from chrRCC at a median 34 months (IQR 15-79) following surgery. PFS and CSS rates at 10 years after surgery were 84% and 90%, respectively. C-indexes for modified AUA and Mayo risk groups were similar at 0.76 and 0.75, respectively, for PFS, and 0.77 and 0.76, respectively for CSS. ConclusionsThe modified AUA and Mayo risk stratification systems have similarly robust c-indexes for PFS and CSS in chrRCC. These models can be used to counsel patients based on pathologic features, inform clinicians on appropriate follow-up pathways, and identify patients at risk of disease progression for enrollment in adjuvant systemic therapy trials.

Postoperative radiotherapy in women with early operable breast cancer (Scottish Breast Conservation Trial): 30-year update of a randomised, controlled, phase 3 trial

Breast-conserving surgery, adjuvant systemic therapy, and radiotherapy are the standard of care for most women with early breast cancer. There are few reports of clinical outcomes beyond the first decade of follow-up of randomised trials comparing breast-conserving surgery with or without radiotherapy. We present a 30-year update of the Scottish Breast Conservation Trial. In this randomised, controlled, phase 3 trial across 14 hospitals in Scotland, women aged younger than 70 years with early breast cancer (tumours ≤4 cm [T1 or T2 and N0 or N1]) were included. They underwent breast-conserving surgery (1 cm margin) with axillary node sampling or clearance. Oestrogen receptor (ER)-rich patients (≥20 fmol/mg protein) received 20 mg oral tamoxifen daily for 5 years. ER-poor patients (<20 fmol/mg protein) received chemotherapy (cyclophosphamide 600 mg/m2, methotrexate 50 mg/m2, and fluorouracil 600 mg/m2 every 21 days intravenously in eight courses). Stratification was by menstrual status (within or more than 12 months from last menstrual period) and ER status (oestrogen concentration ≥20 fmol/mg protein, <20 fmol/mg protein, or unknown) and patients were randomly assigned (1:1) to high-dose (50 Gy in 20-25 fractions) local or locoregional radiotherapy versus no radiotherapy. No blinding was possible due to the nature of the treatment. We report the primary endpoint of the original trial, ipsilateral breast tumour recurrence, and the co-primary endpoint, overall survival. Clinical outcomes were compared by the log-rank test. Hazard ratios (HRs) are reported, with no radiotherapy as the reference group. Failures of the proportional hazards assumption are reported if significant. All analyses are by intention to treat. Between April 1, 1985, and Oct 2, 1991, 589 patients were enrolled and randomly assigned to the two treatment groups (293 to radiotherapy and 296 to no radiotherapy). After exclusion of four ineligible patients (two in each group), there were 291 patients in the radiotherapy group and 294 patients in the no radiotherapy group. Median follow-up was 17·5 years (IQR 8·4-27·9). Ipsilateral breast tumour recurrence was significantly lower in the radiotherapy group than in the no radiotherapy group (46 [16%] of 291 vs 107 [36%] of 294; HR 0·39 [95% CI 0·28-0·55], p<0·0001). Although there were differences in the hazard rate for ipsilateral breast tumour recurrence in the first decade after treatment (HR 0·24 [95% CI 0·15-0·38], p<0·0001), subsequent risks of ipsilateral breast tumour recurrence were similar in both groups (0·98 [0·54-1·79], p=0·95). There was no difference in overall survival between the two groups (median 18·7 years [95% CI 16·5-21·5] in the no radiotherapy group vs 19·2 years [16·9-21·3] in the radiotherapy group; HR 1·08 [95% CI 0·89-1 ·30], log-rank p=0·43). Our findings suggest that patients whose biology predicts a late relapse a decade or more after breast-conserving surgery for early breast cancer might gain little from adjuvant radiotherapy. Breast Cancer Institute (part of Edinburgh and Lothian Health Foundation) and PFS Genomics (now part of Exact Sciences).

Influence of biliary and vascular resection types on morbidity in hepatectomies with vascular involvement.

Hepatectomies associated with vascular resections pose a technical challenge for surgeons, involving multiple reconstruction techniques. Moreover, adding clinical and surgical risks in the postoperative setting of these complex procedures are mainly due to prolonged surgical periods and potential complications inherent to vascular manipulation. Leveraging the expertise of a Cancer Center, we propose an institutional assessment utilizing the case series from A. C. Camargo Cancer Center in hepatectomies associated with vascular resection, evaluating postoperative complications and outcomes while highlighting clinical, laboratory, pathological, and surgical factors that may influence results. To assess mortality and morbidity associated with hepatectomies involving vascular resection. From a prospective database, a study was performed evaluating postoperative survival and morbidity using scoring systems such as Clavien-Dindo through a cohort analysis. From a total of 1021 liver resections for a period of 10 years, 31 cases were evaluated from a unique cancer center in Brazil! Factors such as the performance of major hepatectomies, the need for blood transfusion, and the administration of neoadjuvant or adjuvant systemic therapy did not appear to influence the outcome of morbidity or mortality. However, the resection of the associated bile duct and the type of vascular resection seemed to influence morbidity outcomes with statistical significance (p = 0.006+ …). Hepatectomies associated with vascular resections are safe in selected cases and when performed in referral centers. Factors such as associated bile duct resection and type of vascular resection should be considered for procedure indication.