National assessment of margin status as a quality indicator after pancreatic cancer surgery.

BACKGROUND: Surgical margin involvement is an important outcome after pancreatic cancer surgery; however, variation in pathologic review practices may limit its use as a quality indicator. Our objectives were to assess variation in hospital performance and the reliability of margin involvement after pancreatic cancer surgery. METHODS: From the National Cancer Data Base, patients who underwent pancreatic resection for stage I to III adenocarcinoma were identified. Risk-adjusted surgical margin involvement was evaluated using hierarchical regression methods, and variation in hospital performance and reliability was determined. RESULTS: From 1,002 hospitals, 14,889 patients underwent pancreatic resection for adenocarcinoma, and 3,573 (24.0 %) had an involved surgical margin (R1 22.8 %; R2 1.2 %). The strongest predictors associated with margin involvement were T stage [T3: odds ratio (OR) 2.08, 95 % confidence interval (CI) 1.68-2.59; T4: OR 7.26, 95 % CI 5.50-9.60; vs. T1] and tumor size (2-3.9 cm: OR 1.66, 95 % CI 1.39-1.98, ≥ 4 cm: OR 2.28, 95 % CI 1.90-2.74; vs. <2 cm). Factors associated with a decreased likelihood of margin involvement were the use of neoadjuvant therapy and hospital type (academic and National Cancer Institute-designated comprehensive cancer centers vs. community). At the hospital level, the mean risk-adjusted surgical margin involvement rate was 25.9 % and ranged 10.1 to 50.5 %. Twenty-one (2.1 %) hospitals had lower-than-expected and 17 (1.7 %) had higher-than-expected margin involvement. A minimum acceptable reliability of 0.4 was met after 13 cases and was achieved by 249 hospitals that performed 79 % of pancreatic resections assessed. CONCLUSIONS: Despite differences in pathologic evaluation practices, hospitals can be feasibly and reliably provided comparative data on surgical margin status after resection for pancreatic cancer.

Supportive care considerations during concurrent chemoradiotherapy for pancreatic adenocarcinoma: lessons learned from clinical experience.

Concurrent chemotherapy and radiotherapy (chemoradiotherapy) for the management of pancreatic adenocarcinoma in either adjuvant or locally regional advanced settings produces predictable acute toxicities that are proportional in severity to the intensity and type of systemic therapy and to the parameters of radiotherapy. In addition, relevant to the adjuvant setting, surgery for pancreatic cancer often produces physiologic alterations that may impact a patient's ability to tolerate chemoradiotherapy. Failures to anticipate, monitor, and proactively manage the effects of surgery and toxicities of chemoradiotherapy can result in the need for unplanned treatment interruptions and/or inability to complete all planned therapy. In this review, complications of pancreatic cancer itself and of pancreatic resection as well as toxicities of chemoradiotherapy are delineated, and approaches to their management before, during, and after chemoradiotherapy are presented. Planning for the treatment of side effects before the anticancer therapy begins facilitates therapy administration and improves patient tolerance.

Forphenicinol enhances the antitumor effects of cyclophosphamide in a model of squamous cell carcinoma.

We examined the interaction between forphenicinol (FPL) and cyclophosphamide (CPA) or ionizing radiation (IR) on the growth of murine squamous cell carcinoma tumors SCCVII. Primary tumors were established in C3H mice by injecting SCCVII tumor cells subcutaneously into the right hind limb. FPL (100 mg/kg for 8 days) and/or CPA (25 mg/kg twice) were administered by intraperitoneal injection. Tumors were irradiated to a total dose of 40 Gy (eight 5-Gy fractions). SCCVII tumor growth was inhibited by FPL (P=0.054), IR (P=0.003) and CPA (P<0.001) compared with control. The combination of FPL and CPA inhibited tumor growth additively compared with either treatment alone in both small- and large-volume tumors. FPL did not significantly enhance the antitumor effects of IR, however, when CPA+FPL were combined with IR, significant tumor growth inhibition was observed compared with FPL alone (P<0.001), CPA alone (P=0.002) and IR alone (P=0.002). Due to its low toxicity profile, FPL may be combined with CPA, IR and other cytotoxic therapies to potentially enhance the therapeutic ratio.

Combined gene therapy and ionizing radiation is a novel approach to treat human esophageal adenocarcinoma.

BACKGROUND: The ability to infect tumor cells limits the antitumor effects of gene therapy. The addition of radiotherapy to treatment with Ad.Egr.TNF.11D, a replication-deficient adenovirus containing a radiation-inducible promoter, early growth response-1, and the tumor necrosis factor-alpha (TNFalpha) complementary DNA may enhance the therapeutic ratio. METHODS: Seg-1 human esophageal adenocarcinoma cells were treated with Ad.Egr.TNF.11D with or without radiation. TNFalpha levels were quantified with enzyme-linked immunosorbent assay. Athymic nude mice bearing Seg-1 tumors were randomized to buffer, ionizing radiation, Ad.Egr.TNF.11D, and combination therapy. Tumor growth delay was used to compare treatment regimens. TNFalpha levels were measured in tumor homogenates and plasma. RESULTS: Seg-1 cells treated with Ad.Egr.TNF.11D and ionizing radiation demonstrated increased TNFalpha levels at 72 hours compared with cells exposed to vector alone (124 +/- 0 pg/mL vs. 31.11 +/- 22 pg/mL; P =.008). In vivo, Ad.Egr.TNF.11D-treated tumors expressed low TNFalpha levels (151.5 +/- 107.11 pg/mg protein) compared with tumors receiving combined treatment (793.92 +/- 489.13 pg/mg protein; P =.067). Increased TNFalpha levels were associated with increased tumor growth delay after combined treatment (P <.05). CONCLUSIONS: Radiotherapy enables focal stimulation of TNFalpha expression in Ad.Egr.TNF.11D-infected cells and thus improves local tumor control.