Impact of margin status and lymphadenectomy on clinical outcomes in resected pancreatic adenocarcinoma: implications for adjuvant radiotherapy

Background

Adjuvant chemoradiotherapy (CRT) in the treatment of pancreatic ductal adenocarcinoma (PDA) is controversial. Minimal data exists regarding the clinical significance of margin clearance distance and lymph node (LN) parameters, such as extent of dissection and LN ratio. We assessed the impact of these variables on clinical outcomes to more clearly define the subset of patients who may benefit from adjuvant radiotherapy (RT).

Methods

We identified 106 patients with resected stage 1-3 PDA from 2007-2013. Resection margins were categorized as positive (tumor at ink), ≤1, or >1 mm. LN evaluation included total number examined (NE), number of positive nodes (NP), ratio of NP to NE (NR), extent of dissection, and positive periportal LNs. The impact of these variables was assessed on disease-free survival (DFS) and overall survival (OS) using multivariate cox proportional hazards modeling.

Results

In patients receiving adjuvant chemotherapy (CT) alone, greater margin clearance led to improved DFS (P=0.0412, HR =0.51). Range of NE was 4-37, with a mean of 19. NE was not associated with DFS or OS, yet absolute NP of 5 or more was associated with a significantly worse DFS (P=0.005). Whereas periportal lymphadenectomy did not result in improved DFS or OS, patients with positive periportal LN had worse clinical outcomes (DFS, P=0.0052; OS, P=0.023). The use of adjuvant CRT was associated with improved OS (P=0.049; HR=0.29).

Conclusions

In patients receiving adjuvant CT alone, there was a clinically significant benefit to clearing the surgical margin beyond tumor at ink. Having ≥5 NP and positive periportal LN led to significantly worse clinical outcomes. The addition of adjuvant RT to CT in resected PDA improved OS. A comprehensive evaluation of resection margin distance and LN parameters may identify more patients at risk for locoregional failure who may benefit from adjuvant CRT.     

Overall survival analysis of neoadjuvant chemoradiotherapy and esophagectomy for esophageal cancer

Background

Patients treated with neoadjuvant chemoradiotherapy (NAC) followed by esophagectomy are more likely to have negative margins at resection, be downstaged, and have improved overall survival (OS). The specific aim of this study was to analyze OS outcomes using NAC followed by esophagectomy at a single, tertiary care academic medical center.

Methods

We retrospectively analyzed 106 patients that underwent NAC with platinum-based chemotherapy plus 5-fluorouracil (5-FU) or capecitabine followed by esophagectomy from September 1996 to May 2011. OS was analyzed by the Kaplan Meier method.

Results

Initial staging determined that of 106 patients, 62% had stage III (n=66), 31% stage II (n=33), and 7% had stage I disease (n=7). Following NAC, 92.5% (n=98) were resected with negative (R0) margins and pathologic staging revealed 59% (n=62) were downstaged, 9% (n=10) were upstaged, and 32% (n=34) remained at the same stage. A pathologic complete response (pCR) was achieved in 29% (n=31) of the cohort. Median OS was 35.2 months for all patients, 42 months for downstaged patients, 13 months when upstaged, and 17 months for those who remained at the same stage (P=0.08). OS by histological type was 30 months for adenocarcinoma and 71 months for squamous cell carcinoma (P=0.06).

Conclusions

NAC was effective in downstaging 59% of patients and effectively increased the chance for an R0 resection. These patients, in turn, had improved OS compared to the median OS. Patients with squamous cell carcinoma showed a trend towards more favorable OS.     

Impact of adjuvant treatment modalities on survival outcomes in curatively resected pancreatic and periampullary adenocarcinoma

Background

We examined the impact of adjuvant modalities on resected pancreatic and periampullary adenocarcinoma (PAC).

Methods

A total of 563 patients who were curatively resected for PAC were retrospectively analyzed between 2003 and 2013.

Results

Of 563 patients, 472 received adjuvant chemotherapy (CT) alone, chemoradiotherapy (CRT) alone, and chemoradiotherapy plus chemotherapy (CRT-CT) were analyzed. Of the 472 patients, 231 were given CRT-CT, 26 were given CRT, and 215 were given CT. The median recurrence-free survival (RFS) and overall survival (OS) were 12 and 19 months, respectively. When CT and CRT-CT groups were compared, there was no significant difference with respect to both RFS and OS, and also there was no difference in RFS and OS among CRT-CT, CT and CRT groups. To further investigate the impact of radiation on subgroups, patients were stratified according to lymph node status and resection margins. In node-positive patients, both RFS and OS were significantly longer in CRT-CT than CT. In contrast, there was no significant difference between groups when patients with node-negative disease or patients with or without positive surgical margins were considered.

Conclusions

Addition of radiation to CT has a survival benefit in patients with node-positive disease following pancreatic resection.     

Safety and Feasibility of Carboplatin and Paclitaxel followed by Fluoropyrimidine Analogs and Radiation as Adjuvant Therapy for Gastric Cancer

Background

Adjuvant 5-fluorouracil (5FU)-based chemo-radiotherapy is currently considered a standard of care for the treatment of gastric cancer. The impact of 5FU-based adjuvant therapy on the rate of distant recurrence has been modest. In order to improve the systemic effects of adjuvant therapy, we have been treating patients with resected gastric cancer with carboplatin and paclitaxel followed by fluoropyrimidine analogue and radiation.

Methods

We report on the outcomes of 21 consecutive gastric cancer patients treated off protocol with adjuvant carboplatin (area under the curve 5 mg/ml × min) and paclitaxel (175–200 mg/m²) every 3 weeks, followed by concurrent pyrimidine analogs (either capecitabine 1,600–2,000 mg/m²/day in 17 patients, or 5FU 200 mg/m²/day in 4 patients) and radiation (45–50.4 Gy). Patients received a total of 4–6 cycles of carboplatin and paclitaxel.

Results

The median age at diagnosis was 60 years. Sixteen patients had stage 3 disease and 7 of them had positive surgical margins (6 with R1 and 1 with R2 resection), 3 patients were stage 2, and 2 patients were stage 1 (all had R0 resection). All patients had D1/D2 (4 had D2 and 17 had D1) lymph node dissection. The incidence of grade 3 or higher overall, hematologic, or gastrointestinal toxicity in the patients receiving carboplatin and paclitaxel was 57, 48 and 10%, respectively. No treatment-related deaths were observed. After adjuvant treatment 15 patients developed recurrent disease, 10 of whom had distant metastases. The median recurrence-free survival (RFS) was 12.3 months. The median overall survival (OS) was 16.0 months. Patients with R0 resection had significantly longer OS than did those with positive surgical margins (log-rank p = 0.0060). Median OS for the R0 resection group was 28.8 months.

Conclusions

Carboplatin and paclitaxel added to radiation plus fluoropyrimidine analogs is a well-tolerated regimen in the adjuvant setting. The activity of this regimen in this relatively high-risk group of gastric cancer patients is of interest for future development.Key Words: Paclitaxel, Carboplatin, Adjuvant, Gastric, Radiation     

Management of the right hepatic artery in pancreaticoduodenectomy: a systematic review

Background

The right hepatic artery (RHA) is the most common hepatic artery (CHA) variation. This variation may be problematic in pancreaticoduodenectomy (PD). We aimed to evaluate the impact of the RHA on postoperative and oncological outcomes.

Methods

The PubMed database was systematically searched for comparative studies reporting management of the RHA during PD for the years 1950-2014.

Results

A total of 2,278 patients were analyzed, of whom 440 (19%) had a RHA. The most CHA variation was a replaced RHA. The conservative approach was the most frequently adopted (87%) and only 8% of patients had a sacrifice without reconstruction of the RHA. Postoperative mortality and overall morbidity were similar between patients with and without RHA. Despite the preservation of the RHA in most cases, the rates of microscopic positive margin were also comparable between two groups with no impact of RHA on survival rates.

Conclusions

Postoperative and oncological outcomes seemed unaffected by the RHA in PD. Prospective studies are needed to evaluate its oncological impact.     

Peritoneal dissemination from high-grade appendiceal cancer treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC)

Background

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have shown variability in survival outcomes when used to treat peritoneal surface disease (PSD) from appendiceal and colorectal cancers. The primary goal of this study was to examine outcomes for high-grade appendiceal (HGA) and high-grade colonic primaries after CRS-HIPEC to determine if a significant difference exists between the two groups.

Methods

A retrospective analysis of patients with peritoneal dissemination from appendiceal and colonic primaries were identified in a prospectively maintained database of 1,223 CRS-HIPEC procedures performed between 1991 and 2015. Patient demographics, performance status resection status, tumor grade, nodal status, morbidity, mortality, and survival were reviewed with biopsy-proven PSD being classified according to primary site. Univariate and multivariate analyses were performed, and outcomes compared.

Results

The study identified 171 CRS-HIPEC procedures for 165 patients: 110 (66.7%) for HGA and 55 (33.3%) for high-grade colonic lesions. Observed median disease-free survival (DFS) and overall survival (OS) for both groups were the same at14.4 and 18 months, respectively. Median survival according to resection status for R0/R1, R2a, and R2b/c were 36, 15.6, and 8.4 months (P<0.0001). Median OS for those who received preoperative chemotherapy versus those who did not were 14.4 and 20.4 months, respectively (P=0.01). For those who received preoperative chemotherapy, no difference was apparent in the DFS interval (P=0.34). Multivariate predictors of OS included resection status (P<0.0001) and lymph node involvement (P=0.0005).

Conclusions

Preoperative chemotherapy offered no clear DFS or OS benefit, for HGA or high-grade colon cancer patients. Complete cytoreduction offered the greatest survival benefit to both groups with a correlating drop in survival to resection status. Outcomes for high grade appendiceal cancer are remarkably similar to colon cancer.     

Positive impact of adding No.14v lymph node to D2 dissection on survival for distal gastric cancer patients after surgery with curative intent

Background

D2 lymphadenectomy has been increasingly regarded as standard surgical procedure for advanced gastric cancer (GC), while the necessity of No.14v lymph node (14v) dissection for distal GC is still controversial.

Methods

A total of 920 distal GC patients receiving at least a D2 lymph node dissection in Department of Gastric Cancer, Tianjin Medical University Cancer Institute and Hospital were enrolled in this study, of whom, 243 patients also had the 14v dissected. Other 677 patients without 14v dissection were used for comparison.

Results

Forty-five (18.5%) patients had 14v metastasis. There was no significant difference in 3-year overall survival (OS) rate between patients with and without 14v dissection. Following stratified analysis, in TNM stages I, II, IIIa and IV, 14v dissection did not affect 3-year OS; in contrast, patients with 14v dissection had a significant higher 3-year OS than those without in TNM stages IIIb and IIIc. In multivariate analysis, 14v dissection was found to be an independent prognostic factor for GC patients with TNM stage IIIb/IIIc disease [hazard ratio (HR), 1.568; 95% confidence interval (CI): 1.186-2.072; P=0.002]. GC patients with 14v dissection had a significant lower locoregional, especially lymph node, recurrence rate than those without 14v dissection (11.7% vs. 21.1%, P=0.035).

Conclusions

Adding 14v to D2 lymphadenectomy may be associated with improved 3-year OS for distal GC staged TNM IIIb/IIIc.     

Predictors of positive radial margin status in a population-based cohort of patients with rectal cancer

Background

Surgical margin status is an important predictor of risk of relapse among patients with rectal cancer.

Methods

Patients referred to the British Columbia Cancer Agency for consideration of adjuvant therapy for rectal adenocarcinoma were included. Predictors of margin positivity were determined from uni- and multivariate analysis.

Results

Among 340 patients, 83% had negative resection margins. In 268 patients with resectable tumours, a significantly higher rate of margin positivity was observed in low rectal tumours (32.2%) as compared with mid-rectal (3.9%) and high rectal (14.3%) tumours. Among 59 patients with locally advanced rectal cancer treated with preoperative radiation (with or without chemotherapy), 32% with low tumours had margin positivity. Of patients with T4 tumours, 50% (11/22) had a positive resection margin.

Conclusions

In a population cohort, distal-third rectal location, locally advanced presentation, and T4 cancer represent subgroups for whom further improvement in therapy is required.     

The safety of conization in the management of adenocarcinoma in situ of the uterine cervix

Objective

To evaluate the occurrence of residual or recurrent disease after conization for adenocarcinoma in situ (AIS) of the uterine cervix.

Methods

Medical records of 99 patients with a histologically diagnosis of AIS of the uterine cervix by conization between 1991 and 2008 were reviewed retrospectively.

Results

Seventy eight of 99 patients (78.8%) had negative and 18 (18.2%) had positive resection margins of the conization specimen, and 3 (3.0%) had unknown margin status. Of the 78 patients with negative margins, 45 underwent subsequent hysterectomy and residual AIS were present in 4.4% (2/45) of patients. Ten of the 18 patients with positive margins received subsequent hysterectomy and 3 patients (30%) had residual AIS. Twenty-eight patients had conservative treatment and during the median follow-up time of 23.5 months (range, 7 to 124 months), only one patient (3.6%) had recurrent AIS and was treated with a simple hysterectomy. Eight patients became pregnant after conization, 4 of them delivered healthy babies, one had a spontaneous abortion and 3 were ongoing pregnancies.

Conclusion

Patients with positive resection margins after conization for AIS of the uterine cervix are significantly more likely to have residual disease. However, negative resection margin carries a lower risk for residual AIS, therefore conservative management with careful surveillance seems to be feasible in women who wish to preserve their fertility.     

Intensity-modulated radiotherapy following null-margin resection is associated with improved survival in the treatment of intrahepatic cholangiocarcinoma

Background

The current study is the first to examine the effectiveness and toxicity of postoperative intensity-modulated radiotherapy (IMRT) in the treatment of intrahepatic cholangiocarcinoma (ICC) abutting the vasculature. Specifically, we aim to assess the role of IMRT in patients with ICC undergoing null-margin (no real resection margin) resection.

Methods

Thirty-eight patients with ICC adherent to major blood vessels were included in this retrospective study. Null-margin resection was performed on all patients; 14 patients were further treated with IMRT. The median radiation dose delivered was 56.8 Gy (range, 50-60 Gy). The primary endpoints were overall survival (OS) and disease-free survival (DFS).

Results

At a median follow-up of 24.6 months, the median OS and DFS of all patients (n=38) were 17.7 months (95% CI, 13.2-22.2) and 9.9 months (95% CI, 2.8-17.0), respectively. Median OS was 21.8 months (95% CI, 15.5-28.1) among the 14 patients in the postoperative IMRT group and 15.0 months (95% CI, 9.2-20.9) among the 24 patients in the surgery-only group (P=0.049). Median DFS was 12.5 months (95% CI, 6.8-18.2) in the postoperative IMRT group and 5.5 months (95% CI, 0.7-12.3) in the surgery-only group (P=0.081). IMRT was well-tolerated. Acute toxicity included one case of Grade 3 leukopenia; late toxicity included one case of asymptomatic duodenal ulcer discovered through endoscopy.

Conclusions

The study results suggest that postoperative IMRT is a safe and effective treatment option following null-margin resections of ICC. Larger prospective and randomized trials are necessary to establish postoperative IMRT as a standard practice for the treatment of ICC adherent to major hepatic vessels.     

The role of chemotherapy and/or octreotide in patients with metastatic gastroenteropancreatic and hepatobiliary neuroendocrine carcinoma

Background

Neuroendocrine carcinomas (NECs) of the gastro-entero-pancreatic (GEP) and hepatobiliary (HB) tract are rare and a heterogenous group of malignancies. Octreotide showed the anti-tumor activity in functional and nonfunctional well differentiated metastatic midgut neuroendocrine tumors (NETs). However, the effect of octreotide on survival has not been evaluated.

Patients and methods

We analyzed 17 patients (6 HB- and 11 GEP- tract) with metastatic NEC diagnosed between January 2009 and June 2012. All patients had one or more cytotoxic chemotherapy and nine patients had received octreotide as single agent (n=3) or combination of cytotoxic chemotherapy (n=6).

Results

The median age was 68 years (range, 23-79 years) and median Eastern Cooperative Oncology Group performance status (ECOG PS) was 1. Sixteen of all patients (n=17) received cytotoxic chemotherapy with or without octreotide as the first line therapy and 10 of 16 patients who experienced disease progression to the first line therapy received the second line therapy. Overall response rates (RR) and disease control rates (DCR) to the 1^st line therapy were 41.2% and 76.5%, respectively. The median overall survival (OS) was 16 months [95% confidence interval (CI), 12.8-19.2] and the median OS in patients receiving octreotide during treatment was 40.2 months. In univariate analysis, any clinico-pathologic features including sex, the location of primary tumor, the number of metastatic sites, the debulking operation and the liver metastasis did not have prognostic value regarding OS. However, the use of octreotide offered favorable trend for OS (P=0.091).

Conclusions

The use of octreotide may benefit for patients with GEP- and HB- NECs as a single agent or a combination therapy.     

Autologous hematopoietic stem cell transplantation in chemotherapy-sensitive lymphoblastic lymphoma: treatment outcome and prognostic factor analysis

Objective: The study evaluated the effectiveness of autologous hematopoietic stem cell transplantation(AHSCT) in the treatment of lymphoblastic lymphoma(LL).Methods: We retrospectively analyzed the data from 41 patients with chemotherapy-sensitive LL who underwent hematopoietic stem cell transplantation(HSCT) from December 1989 to December 2009 in a single institution.Results: HSCT was conducted as first-line consolidation therapy and salvage therapy in 36 and 5 patients, respectively. The median follow-up was 97.1 months(range, 24.6-173.1 months). The 5-year overall survival(OS) and event-free survival(EFS) rate were 64% and 47% for the initially treated patients, respectively, and were both 20% for the relapsed ones. Bone marrow(BM) involvement and chemotherapy cycles prior to transplantation were identified as significant prognostic factors for EFS in multivariate analysis.Conclusions: These results confirm that AHSCT is a reasonable option for chemotherapy-sensitive LL patients in first complete remission(CR1).     

Histopathologic tumor response after induction chemotherapy and stereotactic body radiation therapy for borderline resectable pancreatic cancer

Background

While clinical outcomes following induction chemotherapy and stereotactic body radiation therapy (SBRT) have been reported for borderline resectable pancreatic cancer (BRPC) patients, pathologic response has not previously been described.

Methods

This single-institution retrospective review evaluated BRPC patients who completed induction gemcitabine-based chemotherapy followed by SBRT and surgical resection. Each surgical specimen was assigned two tumor regression grades (TRG), one using the College of American Pathologists (CAP) criteria and one using the MD Anderson Cancer Center (MDACC) criteria. Overall survival (OS) and progression free survival (PFS) were correlated to TRG score.

Results

We evaluated 36 patients with a median follow-up of 13.8 months (range, 6.1-24.8 months). The most common induction chemotherapy regimen (82%) was GTX (gemcitabine, docetaxel, capecitabine). A median SBRT dose of 35 Gy (range, 30-40 Gy) in 5 fractions was delivered to the region of vascular involvement. The margin-negative resection rate was 97.2%. Improved response according to MDACC grade trended towards superior PFS (P=061), but not OS. Any neoadjuvant treatment effect according to MDACC scoring (IIa-IV vs. I) was associated with improved OS and PFS (both P=0.019). We found no relationship between CAP score and OS or PFS.

Conclusions

These data suggest that the increased pathologic response after induction chemotherapy and SBRT is correlated with improved survival for BRPC patients.     

Risk factors associated with early recurrence of adenocarcinoma of gastroesophageal junction after curative resection

Objective

To clarify the important clinicopathological factors affecting the early recurrence of adenocarcinoma of esophagogastric junction (AEG).

Methods

We retrospectively reviewed the clinical data of 147 AEG patients who underwent R0 resection during the period from December 1995 to December 2007. Risk factors asssociated with the early recurrence were analyzed by χ² test and logistic regression test.

Results

The mean time to tumor recurrence was 16.3 months after R0 resection, and the 1-year recurrence rate was 48.3%. Univariate analysis showed that the histological grade (poorly and moderately differentiated), number of positive lymph nodes, and vascular invasion were significantly related with the early recurrence (P<0.05). Logistic multivariate regression analysis showed that only histological grade and vascular invasion were independently related with early tumor recurrence (P<0.05).

Conclusions

Histological grade and vascular invasion are independent factors for predicting the early tumor recurrence after R0 resection for AEG.Key Words: Adenocarcinoma of esophagogastric junction (AEG), tumor recurrence, risk factor     

Relationship of ethnicity and overall survival in patients treated with sorafenib for advanced hepatocellular carcinoma

Background

Although both the SHARP and the Asian-Pacific trials showed improved overall survival (OS) for sorafenib, the magnitude of benefit was substantially less for Asians, who have a higher prevalence of hepatitis B viral (HBV) infection. Whether the worse prognosis is related to ethnicity or to the etiology of hepatocellular carcinoma (HCC) remains unclear. The aim of this study was to identify prognostic factors among patients with HCC who received sorafenib in British Columbia (BC), which has a sizeable Asian population.

Methods

A total of 255 consecutive patients with advanced HCC who initiated sorafenib from January 2008 to February 2013 were identified using our pharmacy database. Clinicopathological variables and outcomes were retrospectively collected. Prognostic factors were assessed by univariate and multivariate analyses.

Results

Median age was 63 years, 80.2% were men, and 38% were Asian. Among them, 34.5% had HBV and 29.8% had hepatitis C viral (HCV) infection. In addition, 68.6% had cirrhosis and 45.9% had liver-limited disease. Median progression-free and OS were 3.7 [95% confidence interval (CI): 3.3-4.2] and 7.5 months (95% CI: 5.7-9.2), respectively. On multivariate analysis, Eastern Cooperative Oncology Group performance status (ECOG PS) and HCV positivity correlated with better OS (P<0.001 and 0.04, respectively), but ethnicity did not (P=0.622).

Conclusions

When treated with sorafenib at the same institution, Asians and Caucasians with advanced HCC had similar OS. ECOG PS and HCV were the only significant prognostic factors. A higher proportion of HCV positivity might explain why the SHARP trial achieved better OS when compared to the Asian-Pacific trial.     

Incidence and prognostic impact of high-risk HPV tumor infection in cervical esophageal carcinoma

Background

Cervical esophageal carcinoma (CEC) is an uncommon malignancy. Limited data supports the use of definitive chemoradiotherapy (CRT) as primary treatment. Furthermore, the role of human papillomavirus (HPV) tumor infection in CEC remains unknown. This study retrospectively analyzes both outcomes of CEC patients treated with CRT and the incidence and potential role of HPV tumor infection in CEC lesions.

Methods

A total of 37 CEC patients were treated with definitive CRT at our institution between 1987 and 2013. Of these, 19 had tumor samples available for high-risk HPV (types 16 and 18) pathological analysis.

Results

For all patients (n=37), 5-year overall survival (OS), disease-free survival (DFS), and loco-regional control (LRC) rates were 34.1%, 40.2%, and 65.6%, respectively. On pathological analysis, 1/19 (5.3%) patients had an HPV-positive lesion.

Conclusions

Definitive CRT provides disease-related outcomes comparable to surgery. Moreover, HPV tumor infection in CEC is uncommon and its prognostic role is unclear. Our data contribute to the construction of an anatomical map of HPV tumor infection in squamous cell carcinomas (SCC) of the upper aerodigestive tract, and suggest a steep drop in viral infection rates at sites distal to the oropharynx, including the cervical esophagus.     

Treatment Outcome of Breast Cancer with Pathologically Proven Synchronous Ipsilateral Supraclavicular Lymph Node Metastases

Purpose

The aim of this study was to investigate the prognosis, patterns of failure, and prognostic factors for breast cancer patients with pathologically proven synchronous ipsilateral supraclavicular lymph node (ISCLN) metastases.

Methods

We reviewed the records of breast cancer patients with pathologically proven ISCLN metastases. Local aggressive treatment was defined as treatment including surgery, axillary lymph node dissection (ALND), ISCLN excision, radiotherapy (RT), and chemotherapy.

Results

A total of 111 patients were included. The 5-year overall survival (OS) and disease-free survival (DFS) rates were 64.2% and 56.2%, respectively. On univariate analysis, RT, ALND, trastuzumab treatment, hormone receptor (HR) status, and local aggressive treatment were identified as significant factors for OS. The 5-year OS for 73 patients who received local aggressive treatment was superior to that of 38 patients who received nonaggressive treatment (70.9% vs. 49.3%, p=0.036). Multivariate analysis showed that RT, HR status, and trastuzumab were significant variables for the 5-year OS and DFS.

Conclusion

Multimodality treatment with surgery, taxane-based chemotherapy, hormone therapy, and RT is strongly recommended for breast cancer patients with synchronous ISCLN metastases.     

Trastuzumab beyond progression in HER2-positive advanced breast cancer: the Royal Marsden experience

Background:

Recent UK clinical guidance advises against continuing trastuzumab (T) beyond disease progression (PD) in the absence of brain metastases in patients with HER-2 positive (+ve) advanced breast cancer .We have retrospectively evaluated the outcome of patients with HER-2+ve locally advanced (LA) or metastatic breast cancer (MBC) who continued T beyond PD, treated in our unit.

Methods:

All HER-2+ve patients on our prospectively maintained database with LA or MBC who received T beyond PD after adjuvant or one line of T for advanced disease were assessed for response and outcome. From the timepoint of T continuation beyond PD, we calculated the overall disease control rate, time to progression (TTP), and overall survival (OS).

Results:

One hundred and fourteen patients with HER-2+ve LA or MBC treated with T beyond PD were identified. The main site of disease was visceral_in 84 (74%) patients. Seventy-six (66%) had one line of chemotherapy before continuation of T beyond PD and 21 (19%) had two or more. Post-progression, 66 (58%) received T combined with chemotherapy. Of the 93 (82%) patients with documented clinical or radiological response evaluation, 67 (59%) were considered as having stable disease or better. The median TTP was 24 weeks (95% CI: 21–28) and the median OS was 19 months (95% CI: 12–24).

Conclusion:

Our results from an unselected group of patients provide additional evidence that continuation of T beyond PD is of clinical benefit.     

Prognostic significance of neutrophil-lymphocyte ratio and platelet-lymphocyte ratio in patients treated with selective internal radiation therapy

Background

Elevated neutrophil-to-lymphocyte (NLR) and platelet-to-lymphocyte ratios (PLR) may represent markers of a suboptimal host immune response to cancer and have been shown to correlate with prognosis in multiple tumor types across different treatment modalities, including radiation therapy. Limited data suggest that NLR may predict for survival and disease control in patients receiving selective internal radiation therapy (SIRT). The correlation between clinical outcomes and change in NLR and PLR after SIRT has not been evaluated.

Methods

We retrospectively reviewed 339 consecutive patients with primary (n=37) or metastatic (n=79) liver cancer treated with SIRT from 2006 to 2014. Complete blood counts with differential were available for 116 patients both before and after (median, 29 and 20 days, respectively) SIRT. Survival and progression were calculated from date of initial SIRT. Patient and tumor characteristics evaluated for ability to predict overall survival (OS) and progression free survival (PFS) included pre- and post-treatment neutrophil, platelet, and lymphocyte counts (LCs), as well as NLR, PLR, and relative change in NLR and PLR. Cutoff values were determined for variables that were significant on multivariate analysis (MVA) for OS and/or PFS.

Results

Median follow-up of surviving patients was 12 months. Median OS was 8 months from SIRT and 20 months from date of liver metastasis diagnosis. Significant factors on univariate analysis (UVA) for both lower OS and PFS included higher post-treatment neutrophil count (NC), higher post-treatment NLR, higher liver tumor volume, higher percentage liver tumor burden, and worse Eastern Cooperative Oncology Group (ECOG) performance status. Significant factors on MVA for lower OS and PFS were ECOG performance status ≥2, higher liver tumor volume, higher pretreatment PLR, and increase in PLR after SIRT. Post-treatment increase in PLR >3-fold was the most predictive early marker for increased risk of death when compared with those whose PLR did not increase or increased <3-fold. Pretreatment PLR >78 was the most predictive serum marker associated with improved OS prior to therapy.

Conclusions

This is the largest study to evaluate the association between NLR and PLR with clinical outcomes in patients receiving SIRT, with results that confirm that pre- and/or post-treatment NLR and/or PLR are predictive of clinical outcomes. The largest increase in risk of death as well as local and extrahepatic disease progression was related to change in PLR, a datum not well reported in the literature. The impact of SIRT on blood count changes and the underlying implications of these ratios should be further characterized in a prospective study.