Background
Pathologic response to preoperative chemotherapy predicts survival in patients with colorectal liver metastases (CLMs) who undergo hepatectomy. In multiple CLMs, mixed pathologic response, ...wherein tumors exhibit different degrees of treatment response, is possible. We sought to evaluate survival outcomes of mixed response in patients with multiple CLMs.
Methods
We conducted a retrospective cohort study using a single-institution database of patients with two or more CLMs who underwent preoperative chemotherapy and hepatectomy (2010–2018). Pathologic response of each tumor was measured on pathology. Patients were stratified by pathologic response as complete (pCR) = 0–1% viability; major (pMajR) = 2–49% viability; minor (pMinR) = 50–99% viability; or mixed (pMixR) = at least one pCR/MajR tumor and one pMinR. Recurrence-free survival (RFS) and overall survival (OS) were estimated using the Kaplan–Meier method, and adjusted risk of death was evaluated using Cox regression.
Results
Among 444 patients, 6% had pCR, 34% had pMajR, 36% had pMinR, and 24% had pMixR. Median and 5-year RFS for patients with pMixR was 10.4 months and 16%, respectively, compared with pMajR (11.3 months and 18%, respectively), pMinR (7.7 months and 13%, respectively), and pCR (23.1 months and 38%, respectively) log-rank
p
< 0.001. Median and 5-year OS for patients with pMixR was 77.4 months and 60%, respectively, compared with pMajR (80.5 months and 63%, respectively), pMinR (49.9 months and 39%, respectively), and pCR (median OS not reached; median follow-up of 37.1 months and 5-year OS of 65%) log-rank
p
= 0.002. pMixR was associated with a 52% risk of death reduction (hazard ratio 0.48, 95% confidence interval 0.30–0.78 vs. pMinR).
Conclusions
One-quarter of patients with multiple CLMs have pMixR following preoperative chemotherapy and hepatectomy. OS and RFS for patients with pMixR mirror those of pMajR rather than pMinR, suggesting the greatest response achieved in any metastasis best predicts survival.
While risk-stratified post-hepatectomy pathways (RSPHPs) reduce length-of-stay, can they stratify hepatectomy patients by risk of early postoperative events.
90-day outcomes from consecutive ...hepatectomies were analyzed (1/1/2017–12/31/2021). Pre/post-pathway analysis was performed for pathways: minimally invasive surgery (“MIS”); non-anatomic resection/left hepatectomy (“low-intermediate risk”); right/extended hepatectomy (“high-risk”); “Combination” operations. Time-to-event (TTE) analyses for readmission and interventional radiology procedures (IRPs) was performed.
1354 patients were included: MIS/n= 119 (9 %); low-intermediate risk/n= 443 (33 %); high-risk/n= 328 (24 %); Combination/n= 464 (34 %). There was no difference in readmission (pre: 13 % vs. post:11.5 %, p = 0.398). There were fewer readmissions in post-pathway patients amongst MIS, low-intermediate risk, and Combination patients (all p > 0.1). 114 (8.4 %) patients required IRPs. Time-to-readmission and time-to-IR-procedure plots demonstrated lower plateaus and flatter slopes for MIS/low-intermediate-risk pathways post-pathway implementation (p < 0.001).
RSPHPs can reliably stratify patients by risks of readmission or need for an IR procedure by predicting the most frequent period for these events.
•RSPHPs stratify patients by risk of readmission or need for IR procedure by predicting the frequency of these events.•Knowledge of hepatectomy complexity and risk of complications informs intensity of postoperative follow-up after hepatectomy.•Utilization of telehealth for lower risk patients may minimize loss of time and money while maintaining excellent outcomes.
Purpose
Most patients with intrahepatic cholangiocarcinoma (IHCC) develop recurrence after resection. Adjuvant capecitabine remains the standard of care for resected IHCC. A combination of ...gemcitabine, cisplatin, and nab-paclitaxel (GAP) was associated with a 45% response rate and 20% conversion rate among patients with unresectable biliary tract cancers. The aim of this study was to evaluate the feasibility of delivering GAP in the neoadjuvant setting for resectable, high-risk IHCC.
Methods
A multi-institutional, single-arm, phase II trial was conducted for patients with resectable, high-risk IHCC, defined as tumor size > 5 cm, multiple tumors, presence of radiographic major vascular invasion, or lymph node involvement. Patients received preoperative GAP (gemcitabine 800 mg/m
2
, cisplatin 25 mg/m
2
, and nab-paclitaxel 100 mg/m
2
on days 1 and 8 of a 21-day cycle) for a total of 4 cycles prior to an attempt at curative-intent surgical resection. The primary endpoint was completion of both preoperative chemotherapy and surgical resection. Secondary endpoints were adverse events, radiologic response, recurrence-free survival (RFS), and overall survival (OS).
Results
Thirty evaluable patients were enrolled. Median age was 60.5 years. Median follow-up for all patients was 17 months. Ten patients (33%) experienced grade ≥ 3 treatment-related adverse events, the most common being neutropenia and diarrhea; 50% required ≥ 1 dose reduction. The disease control rate was 90% (progressive disease: 10%, partial response: 23%, stable disease: 67%). There was zero treatment-related mortality. Twenty-two patients (73%, 90% CI 57–86;
p
= 0.008) completed all chemotherapy and surgery. Two patients (9%) who successfully underwent resection had minor postoperative complications. Median length of hospital stay was 4 days. Median RFS was 7.1 months. Median OS for the entire cohort was 24 months and was not reached in patients who underwent surgical resection.
Conclusion
Neoadjuvant treatment with gemcitabine, cisplatin, and nab-paclitaxel is feasible and safe prior to resection of intrahepatic cholangiocarcinoma and does not adversely impact perioperative outcomes.
Background
We evaluated the associations of surgical margin status and somatic mutations with the incidence of local recurrence (LR) and oncologic outcomes in patients undergoing R0-intent ...(microscopically negative margin) resection of colorectal liver metastases (CLM).
Methods
Patients with CLM who underwent initial R0-intent resection and analysis of tumor tissue using next-generation sequencing during 2001–2018 were analyzed. Recurrences were classified as LR (at the resection margin), other intrahepatic recurrence, or extrahepatic recurrence. Predictors and survival effect of LR were evaluated using univariate and multivariate analysis.
Results
Of 552 patients analyzed, 415 (75%) had R0 resection (margin width ≥ 1.0 mm), and 38 (7%) had LR. LR incidence was not affected by surgical margin width.
RAS
/
TP53
co-mutation was associated with increased risk of intrahepatic recurrence (67% vs. 49%;
p
< 0.001) and overall recurrence (
p
< 0.001). However, incidence of LR did not differ significantly by
RAS
/
TP53
,
BRAF
,
SMAD4
, or
FBXW7
mutation. Extrahepatic disease (hazard ratio HR, 1.47;
p
= 0.034), > 8 cycles of preoperative chemotherapy (HR, 1.98;
p
= 0.033), tumor viability ≥ 50% (HR, 1.55;
p
= 0.007),
RAS
/
TP53
co-mutation (HR, 1.69;
p
= 0.001), and
SMAD4
mutation (HR, 2.44;
p
< 0.001) were independently associated with poor overall survival, but surgical margin status was not.
Conclusions
Although somatic mutations were associated with overall recurrence, neither surgical margin width nor somatic mutations affected LR risk after R0-intent hepatectomy for CLM. LR and prognosis were likely driven by individual tumor biology rather than surgical margins.
Multidisciplinary hepatocellular carcinoma (HCC) treatment is associated with optimal outcomes. There are few data analyzing the impact of treating hospitals' therapeutic offerings on survival. We ...performed a retrospective cohort study of patients aged 18‐70 years with HCC in the National Cancer Database (2004‐2012). Hospitals were categorized based on the level of treatment offered (Type I—nonsurgical; Type II—ablation; Type III—resection; Type IV—transplant). Associations between overall risk of death and hospital type were evaluated with multivariable Cox shared frailty modeling. Among 50,381 patients, 65% received care in Type IV hospitals, 26% in Type III, 3% in Type II, and 6% in Type I. Overall 5‐year survival across modalities was highest at Type IV hospitals (untreated: Type IV—13.1% versus Type I—5.7%, Type II—7.0%, Type III—7.4% log‐rank, P < 0.001; chemotherapy and/or radiation: Type IV—18.1% versus Type I—3.6%, Type II—4.6%, Type III—7.7% log‐rank, P < 0.001; ablation: Type IV—33.3% versus Type II—13.6%, Type III—23.6% log‐rank, P < 0.001; resection: Type IV—48.4% versus Type III—39.1% log‐rank, P < 0.001). Risk of death demonstrated a dose‐response relationship with the hospital type—Type I (ref); Type II (hazard ratio HR 0.81, 95% confidence interval 0.73‐0.90); Type III (HR 0.67 0.62‐0.72); Type IV hospitals (HR 0.43 0.39‐0.47). Conclusion: Although care at hospitals offering the full complement of HCC treatments is associated with decreased risk of death, one third of patients are not treated at these hospitals. These data can inform the value of health policy initiatives regarding regionalization of HCC care.
Background Differentiated thyroid carcinomas (DTC) are the only tumors for which age is a determinant of stage in the American Joint Committee on Cancer’s (AJCC) staging protocol. In this study, we ...re-examined the relationship between age, extent of disease, and prognosis by using a large dataset with longer follow-up times. Methods We examined the Surveillance, Epidemiology, and End Results (SEER) registry data 1973 to 2005 for patients with DTC as their only known malignancy. We used Cox multivariate analyses to generate mortality hazard ratios, controlling for several variables, to evaluate the effects of age and disease extent. Results We identified 55,402 patients with DTC. Of these, 49,240 had sufficient data to generate a TNM stage on the basis of AJCC guidelines. Within stage II, younger patients (<45 years) have worse outcomes than older patients ( P < .001). Younger patients had an 11-fold increase in mortality between stages I and II, whereas there was no difference for older patients. When we uniformly applied the 45-and-older staging protocol to all patients, we found that stages III-IVc had a significantly greater risk of mortality for all patients compared with stage I. Conclusion The presence of regional and metastatic thyroid cancer bears prognostic significance for all ages. Under current AJCC guidelines, young patients with metastatic thyroid cancer may be understaged.
Significance: The use of cancer-targeted contrast agents in fluorescence-guided surgery (FGS) has the potential to improve intraoperative visualization of tumors and surgical margins. However, ...evaluation of their translational potential is challenging.
Aim: We examined the utility of a somatostatin receptor subtype-2 (SSTR2)-targeted fluorescent agent in combination with a benchtop near-infrared fluorescence (NIRF) imaging system to visualize mouse xenografts under conditions that simulate the clinical FGS workflow for open surgical procedures.
Approach: The dual-labeled somatostatin analog, Ga67-MMC(IR800)-TOC, was injected into mice (n = 24) implanted with SSTR2-expressing tumors and imaged with the customized OnLume NIRF imaging system (Madison, Wisconsin). In vivo and ex vivo imaging were performed under ambient light. The optimal dose (0.2, 0.5, and 2 nmol) and imaging time point (3, 24, 48, and 72 h) were determined using contrast-to-noise ratio (CNR) as the image quality parameter. Video captures of tumor resections were obtained to provide an FGS readout that is representative of clinical utility. Finally, a log-transformed linear regression model was fitted to assess congruence between fluorescence readouts and the underlying drug distribution.
Results: The drug–device combination provided high in vivo and ex vivo contrast (CNRs > 3, except lung at 3 h) at all time points with the optimal dose of 2 nmol. The optimal imaging time point was 24-h post-injection, where CNRs > 6.5 were achieved in tissues of interest (i.e., pancreas, small intestine, stomach, and lung). Intraoperative FGS showed excellent utility for examination of the tumor cavity pre- and post-resection. The relationship between fluorescence readouts and gamma counts was linear and strongly correlated (n = 334, R2 = 0.71; r = 0.84; P < 0.0001).
Conclusion: The innovative OnLume NIRF imaging system enhanced the evaluation of Ga67-MMC(IR800)-TOC in tumor models. These components comprise a promising drug–device combination for FGS in patients with SSTR2-expressing tumors.
OBJECTIVE:The aim of the study was to evaluate the impact of receiving care at high minimally invasive surgery (MIS)-utilizing hospitals
BACKGROUND:MIS techniques are used across surgical ...specialties. The extent of MIS utilization for gastrointestinal (GI) cancer resection and impact of receiving care at high utilizing hospitals is unclear.
METHODS:This is a retrospective cohort study of 137,581 surgically resected esophageal, gastric, pancreatic, hepatobiliary, colon, and rectal cancer patients within the National Cancer Data Base (2010–2013). Disease-specific, hospital-level, reliability-adjusted MIS utilization rates were calculated to evaluate perioperative outcomes. Among patients for whom adjuvant chemotherapy (AC) was indicated, the association between days to AC and hospital MIS utilization was examined using generalized estimating equations. Association with risk of death was evaluated using multivariable Cox regression.
RESULTS:Disease-specific MIS use increased significantly 42.0%–68.3% increase; trend test, P < 0.001 for all except hepatobiliary (P = 0.007) over time. Most hospitals range—30.3% (colon); 92.9% (pancreatic) were low utilizers (≤30% of cases). Higher MIS utilization is associated with increased lymph nodes examined (P < 0.001, all) and shorter length of stay (P < 0.001, all). Each 10% increase in MIS utilization is associated with fewer days to AC 3.3 (95% confidence interval, 1.2–5.3) for MIS gastric; 3.3 (0.7–5.8) for open gastric; 1.1 (0.3–2.0) days for open colon. An association between MIS utilization and risk of death was observed for colon Q2—hazard ratio (HR) 0.96 (0.89–1.02); Q3—HR 0.91 (0.86–0.98); Q4—HR 0.87 (0.82–0.93) and rectal cancer Q2—HR 0.89 (0.76–1.05); Q3—HR 0.84 (0.82–0.97); Q4—HR 0.86 (0.74–0.98).
CONCLUSIONS:Most hospitals treating GI malignancies are low MIS utilizers. Our findings may reflect real-world MIS effectiveness for oncologic resection and could be useful for identifying hospitals with infrastructure and/or processes beneficial for multimodality cancer care.
Lymphatic spread of intrahepatic cholangiocarcinoma (iCCA) is common and negatively impacts survival. However, the precise role of lymph node dissection (LND) in oncologic outcomes for patients with ...intrahepatic cholangiocarcinoma remains to be established.
Updated evidence on the preoperative diagnosis and prognostic value of lymph node metastasis is reviewed, as well as the potential benefit of LND in patients with iCCA.
The ability to accurately determine nodal status for iCCA with current imaging modalities is equivocal. LND has prognostic value for both survival and disease recurrence. However, execution rates of LND are highly varied in the literature, ranging from 26.9 to 100%. At least 6 lymph nodes should be examined from nodal stations of the hepatoduodenal ligament and hepatic artery as well as based on the location of the primary tumor. Neoadjuvant therapies may be beneficial if lymph node metastases at diagnosis are suspected. Surgeons performing a minimally invasive approach should focus on increasing LND rates and harvesting ≥ 6 lymph nodes. Lymph node negativity is required in patients with iCCA being considered for liver transplantation under investigational protocols.
Despite an upward trend in the LND rate, the reality is that only 10% of patients with iCCA receive an adequate LND. This review underscores the importance of routinely increasing the rate of adequate LND in these patients in order to achieve accurate staging, appropriately select patients for adjuvant therapy, and improve the prognosis of clinical outcomes. While prospective data is lacking, the therapeutic impact of LND remains unknown.
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