Person:

Hong, Theodore

Background: Neoadjuvant therapy may affect the prognostic impact of total lymph node harvests and lymph node positivity after surgery for rectal cancer. Methods: We performed a retrospective review of 390 consecutive patients with histologically confirmed rectal cancer. Postoperative follow-up evaluation and survival were confirmed via medical record review. The impacts of lymph node positivity and total lymph node harvest on survival and recurrence are reflected as proportional hazard ratios (HRs). Results: A total of 221 patients underwent neoadjuvant therapy, of whom 75 had positive nodes. Node-positive patients showed a significantly shorter survival time (HR, 2.89; P = .002) and time to local recurrence (HR, 6.36; P = .031) compared with patients without positive nodes. Survival and recurrence were not significantly different between patients with a total harvest of fewer than 12 nodes and patients with a higher lymph node harvest. Conclusions: After neoadjuvant treatment and total mesorectal excision, lymph node positivity is associated with significantly shorter survival and time to local recurrence in rectal cancer patients, whereas absolute total lymph node harvests likely have little impact on prognosis.

Objective: Patients who undergo an R0 resection of their pancreatic ductal adenocarcinoma (PDAC) have an improved survival compared with patients who undergo an R1 resection. It is unclear whether an R1 resection confers a survival benefit over locally advanced (LA) unresectable tumors. Our aim was to compare the survival of patients undergoing an R1 resection with those having LA tumors and to explore the prognostic significance of a 1-mm surgical margin. Methods: Clinicopathologic data from a pancreatic cancer database between January 1993 and July 2008 were reviewed. Locally advanced tumors had no evidence of metastatic disease at exploration. Results: A total of 1705 patients were evaluated for PDAC in the Department of Surgery. Of the 1084 (64%) patients who were surgically explored, 530 (49%) were considered unresectable (286 locally unresectable, 244 with distant metastasis). One hundred fifty-seven (28%) of the resected PDACs had an R1 resection. Patients undergoing an R1 resection had a slightly longer survival compared with those who had locally advanced unresectable cancers (14 vs 11 months; P < 0.001). Patients with R0 resections had a favorable survival compared with those with R1 resections (23 vs 14 months; P < 0.001), but survival after resections with 1-mm margin or less (R0-close) were similar to R1 resections: both groups had a significantly shorter median survival than patients with a margin of greater than 1 mm (R0-wide) (16 vs 14 vs 35 months, respectively; P < 0.001). Conclusions: Patients undergoing an R1 resection still have an improved survival compared with patients with locally advanced unresectable pancreatic adenocarcinoma. R0 resections have an improved survival compared with R1 resections, but this survival benefit is lost when the tumor is within 1 mm of the resection margin.

Background: The benefit of surgical resection in patients with incurable gastric adenocarcinoma is controversial. Methods: A total of 289 patients who presented with advanced or metastatic gastric cancer from 1995 to 2010 were retrospectively reviewed. Results: Ten patients (3.5 %) required emergent surgery at presentation and were excluded from further analyses. Patients who underwent nonemergent surgery at presentation (n = 110, 38.1 %) received either gastric resection (group A, n = 46, 42 %) or surgery without resection (group B, n = 64, 58 %). Procedures in group A included distal gastrectomy (n = 25, 54 %), total gastrectomy (n = 17, 37 %), and proximal/esophagogastrectomy (n = 4, 9 %). Procedures in group B included laparoscopy (n = 17, 27 %), open exploration (n = 25, 39 %), gastrostomy and/or jejunostomy tube (n = 12, 19 %), and gastrojejunostomy (n = 10, 16 %). Group A required a stay in the intensive care unit or additional invasive procedure significantly more often than group B (15 vs. 2 %, p = 0.009). Four patients in group A (8.7 %) and three patients in group B (4.7 %) died within 30 days of surgery (p = 0.45). When the 110 patients who underwent nonemergent surgery (groups A and B) were compared to nonoperatively managed patients (group C, n = 169, 58 %), median overall survival did not significantly differ (8.6 vs. 9.2 vs. 7.7 months; p > 0.05). Three patients in group B (4.7 %) and three in group C (1.8 %) ultimately required an operation for their primary tumor. Conclusions: Patients with gastric adenocarcinoma who present with advanced or metastatic disease not amenable to curative resection infrequently require emergent surgery. Noncurative resection is associated with significant perioperative morbidity and mortality as well as limited overall survival, and should therefore be performed judiciously.

Purpose

To evaluate the feasibility of a respiratory-gated proton beam therapy for liver tumors.

Materials and Methods

Fifteen patients were enrolled on a prospective IRB-approved protocol. Eligibility criteria included Childs-Pugh A/B cirrhosis, unresectablebiopsy-proven hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), or metastatic disease (solid tumors only), 1-3 lesions, and tumor size of ≤6 cm. Patients received 15 fractions to a total dose of 45-75 GyE using respiratory-gated proton beam therapy. Gating was performed with an external respiratory position monitoring (RPM) based system.

Results

Of the15 patients enrolled on this clinical trial, 11 had HCC, 3 had ICC, and 1had metastasis from another primary. Ten patients had a single lesion, 3 patients had 2 lesions, and 2 patients 3 lesions. Toxicities were: Gr 3 bilirubinemia- 2, Gr 3 gastrointestinal bleed- 1, and Gr 5 stomach perforation-1. One patient had a marginal recurrence, 3 had hepatic recurrences elsewhere in the liver, and 2 had extrahepatic recurrence. With a median follow-up for survivors of 69 months, 1-yr, 2-yr, 3-yr OS is 53%, 40%, and 33% respectively. PFS is 40%,33% and 27% at 1, 2, and 3 years, respectively.

Conclusion

Respiratory-gated proton beam therapy for liver tumors is feasible. Phase II studies for primary liver tumors and metastatic tumorsare underway.

Gated radiation therapy is a promising method for improving the dose conformality of treatments to moving targets and reducing the total volume of irradiated tissue. Target motion is of particular concern in proton beam radiotherapy, due to the finite range of proton dose deposition in tissue. Gating allows one to reduce the extent of variation, due to respiration, of the radiological depth to target during treatment delivery. However, respiratory surrogates typically used for gating do not always accurately reflect the position of the internal target. For instance, a phase delay often exists between the internal motion and the motion of the surrogate. Another phenomenon, baseline drifting refers to a gradual change in the exhale position over time, which generally affects the external and internal markers differently. This study examines the influence of these two physiological phenomena on gated radiotherapy using an external surrogate.

During cancer therapy, tumor heterogeneity can drive the evolution of multiple tumor subclones harboring unique resistance mechanisms in an individual patient1-3. Prior case reports and small case series have suggested that liquid biopsy (specifically, cell-free DNA (cfDNA)) may better capture the heterogeneity of acquired resistance4-8. However, the effectiveness of cfDNA versus standard single-lesion tumor biopsies has not been directly compared in larger scale prospective cohorts of patients following progression on targeted therapy. Here, in a prospective cohort of 42 patients with molecularly-defined gastrointestinal cancers and acquired resistance to targeted therapy, direct comparison of post-progression cfDNA versus tumor biopsy revealed that cfDNA more frequently identified clinically-relevant resistance alterations and multiple resistance mechanisms, detecting resistance alterations not found in the matched tumor biopsy in 78% of cases. Whole-exome sequencing of serial cfDNA, tumor biopsies, and rapid autopsy specimens elucidated substantial geographic and evolutionary differences across lesions. Our data suggest that acquired resistance is frequently characterized by profound tumor heterogeneity, and that the emergence of multiple resistance alterations in an individual patient may represent the “rule” rather than the “exception.” These findings have profound therapeutic implications and highlight the potential advantages of cfDNA over tissue biopsy in the setting of acquired resistance.