Category Archives: Oncology

ONCOTYPE IQ for DCIS: A 12-year update on the ECOG-ACRIN E5194 study

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One discussion last week included Dr. Wood’s ONCOTYPE IQ for DICS, Trial E5194.

Reference: Solin LJ, et al. Surgical excision without radiation for ductal carcinoma in situ of the breast: 12-year results from the ECOG-ACRIN E5194 study. Journal of Clinical Oncology. 2015 Nov 20;33(33):3938-3944. doi: 10.1200/JCO.2015.60.8588

ClinicalTrials.gov NCT00002934.

Summary: The Eastern Cooperative Oncology Group–American College of Radiology Imaging Network (ECOG-ACRIN; formerly the Eastern Cooperative Oncology Group) Cancer Research Group E5194 study (a nonrandomized clinical trial) prospectively enrolled patients for whom surgical excision alone (without radiation) was thought to be a reasonable treatment option on the basis of low-risk clinical and pathologic characteristics. This report provides updated results from the ECOG-ACRIN E5194 study, including 10- and 12-year outcomes.

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The ACOSOG Z0011 Randomized Control Trial

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One discussion last week included the ACOSOG Z0011 RCT.

Reference: Giuliano AE, et al. Effect of axillary dissection vs no axillary dissection on 10-year overall survival among women with invasive breast cancer and sentinel node metastasis: the ACOSOG Z0011 (Alliance) randomized control trial. JAMA. 2017 Sep 12;318(10):918-926. doi: 10.1001/jama.2017.11470.

Summary: The results of the American College of Surgeons Oncology Group Z0011 (ACOSOG Z0011) trial were first reported in 2005 with a median follow-up of 6.3 years. Longer follow-up was necessary because the majority of the patients had estrogen receptor-positive tumors that may recur later in the disease course. In this follow-up study, the authors sought to determine whether the 10-year overall survival of patients with 2 or fewer sentinel lymph node metastases treated with breast-conserving therapy and sentinel lymph node dissection (SLND) alone without axillary lymph node dissection (ALND) is noninferior to that of women treated with axillary dissection.

Compared with ALND, SLND alone was found to be noninferior for overall survival. The 10-year overall survival rate was 86.3% in the SLND alone group and 83.6% in the ALND group. The unadjusted HR comparing overall survival between the SLND alone group and the ALND group was 0.85 (1-sided 95% CI, 0–1.16), which did not cross the prespecified noninferiority HR margin of 1.3. The HR for overall survival adjusting for adjuvant therapy (chemotherapy, endocrine therapy, radiation, or a combination of these 3) and age for the SLND alone group compared with the ALND group was 0.93 (1-sided 95% CI, 0–1.28) (Table 2).

10yr survival

CONCLUSION: In this randomized clinical trial including 856 women, after median follow-up of 9.3 years, overall survival for patients treated with sentinel lymph node dissection alone was not inferior to those treated with completion axillary lymph node dissection (86.3% vs 83.6%, respectively; noninferiority hazard ratio margin of 1.3). These findings do not support the use of axillary lymph node dissection when 2 or fewer metastases are found with sentinel lymph node sampling in women with cT1-2M0 breast cancer.

Lobectomy vs total thyroidectomy for intermediate-size papillary thyroid cancer

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One discussion last week included the extent of surgery for intermediate-size papillary thyroid cancer: lobectomy vs total thyroidectomy.

Reference: Adam MA, et al. Extent of surgery for papillary thyroid cancer is not associated with survival: an analysis of 61,775 patients. Annals of Surgery. 2014 Oct;260(4):601-605. doi:10.1097/SLA.0000000000000925.

Summary: Guidelines recommend total thyroidectomy for PTC tumors >1 cm, based on older data demonstrating an overall survival advantage for total thyroidectomy over lobectomy.

Adult patients with PTC tumors 1.0-4.0 cm undergoing thyroidectomy in the National Cancer Database between 1998-2006 were included, totaling 61,775 patients. Median follow-up was 82 months (range, 60-179 months).

Lobectomy (n=6849)

Total thyroidectomy (n=54,926)
Nodal disease

7%

27%
Extrathyroidal disease

5%

16%
Multifocual disease

29%

44%

After multivariable adjustment, overall survival was similar in patients undergoing total thyroidectomy versus lobectomy for tumors 1.0-4.0 cm and when stratified by tumor size: 1.0-2.0 cm and 2.1-4.0 cm. Older age, male sex, black race, lower income, tumor size, and presence of nodal or distant metastases were independently associated with compromised survival (P < 0.0001).

Adam et al (2014) conclude that although current guidelines suggest total thyroidectomy for PTC tumors >1 cm, they did not observe a survival advantage associated with total thyroidectomy compared with lobectomy. These findings call into question whether tumor size should be an absolute indication for total thyroidectomy.

Early vs late drain removal after pancreatectomy

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One discussion this week included early vs late drain removal in pancreatectomy.

References: Beane JD, et al. Variation of drain management after pancreatoduodenectomy: early versus delayed removal. Annals of Surgery. 2017 Oct. doi: 10.1097/SLA.0000000000002570

Deminski J, et al. Early removal of intraperitoneal drainage after pancreatoduodenectomy in patients without postoperative fistula at POD3: results of a randomized clinical trial. Journal of Visceral Surgery. 2019 Jan 31. pii: S1878-7886(18)30084-5. doi: 10.1016/j.jviscsurg.2018.06.006

Summary:  Early drain removal after pancreatoduodenectomy, when guided by postoperative day (POD) 1 drain fluid amylase (DFA-1), is associated with reduced rates of clinically relevant postoperative pancreatic fistula (CR-POPF).

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What is the composition of seroma fluid?

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One discussion this week included the composition of post-surgical seroma fluid.

Reference: Valeta-Magara A, et al. Pro-oncogenic cytokines and growth factors are differently expressed in the post-surgical wound fluid from malignant compared to benign breast lesions. SpringerPlus. 2015 Sep 5;4:483. doi:10.1186/s40064-015-1260-8.

Summary: Post-operative accumulation of seroma in the surgical cavity following breast cancer surgery varies in incidence from 2.5 to 51 % of patients. Analysis of seroma has shown that it is an inflammatory exudate, classically seen in the first phase of wound repair. Given that seroma is derived from the wound-healing response of tumor-adjacent stroma, Valeta-Magara et al (2015) explored “whether seroma derived from the excision of benign tumors differs from that of malignant tumors, as malignant and benign tumors may activate or influence the adjacent stroma and infiltrating immune cells differently.”

Post-surgical seroma fluids from 59 patients who had undergone either lumpectomy or mastectomy breast surgery were collected at week 1 or 2 post-surgery by percutaneous aspiration.

It was found that surgical cavity seroma from breast cancer patients has ahigher expression of certain tumorpromoting cytokines, including GRO, ENA-78/CXCL5 and TIMP-2, and lower expression of tumor-inhibiting cytokines IGFBP-1, IL-16, IFN-γ, IL-3 and FGF-9, when compared to seroma from non-cancer patients (p.2). Patients with high body mass index also had higher levels of leptin regardless of malignancy.

In conclusion, breast post-surgical tumor cavity contains factors that are pro-inflammatory regardless of malignant or benign disease, but in malignant disease there is significant enrichment of additional pro-oncogenic chemokines, cytokines and growth factors, and reduction in tumor-inhibiting factors. These results are consistent with tumor conditioning of surrounding normal stromal tissue and creation of a pro-oncogenic environment that persists long after surgical removal of the tumor.

The authors also note that a differential expression of the eight factors between benign and malignant seroma fluid offers research hypotheses to be explored further to determine their role in breast tumor progression, local recurrence and metastasis.

 

Perioperative fluid management: restrictive vs liberal regimens

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One discussion this week included restrictive vs liberal perioperative fluid management on the development of perioperative acute kidney injury.

References: Brandstrup B, et al. Effects of intravenous fluid restriction on postoperative complications: comparison of two perioperative fluid regimens: a randomized assessor-blinded multicenter trial. Annals of Surgery. 2003 Nov;238(5):641-648.

Myles PS, et al. Restrictive versus liberal fluid therapy for major abdominal surgery. NEJM. 2018 Jun 14;378:2263-2274. doi:10.1056/NEJMoa1801601

Summary: Traditional intravenous-fluid regimens administered during abdominal surgery deliver up to 7 liters of fluid on the day of surgery. Some small trials have shown that a more restrictive fluid regimen led to fewer complications and a shorter hospital stay. However, the evidence for fluid restriction during and immediately after abdominal surgery is inconclusive. Fluid restriction could increase the risk of hypotension and decrease perfusion in the kidney and other vital organs, leading to organ dysfunction, but excessive intravenous-fluid infusion may increase the risk of pulmonary complications, acute kidney injury, sepsis, and poor wound healing (Myles 2018).

Each of the RCTs below compare restrictive vs liberal fluid management, with conflicting conclusions.

BRANDSTRUB ET AL (2003)

This multicenter RCT involved 172 patients allocated to either a restricted or a standard intraoperative and postoperative intravenous fluid regimen. The restricted regimen aimed at maintaining preoperative body weight; the standard regimen resembled everyday practice. The primary outcome measures were complications; the secondary measures were death and adverse effects.

Results: The restricted intravenous fluid regimen significantly reduced postoperative complications both by intention-to-treat (33% versus 51%, P = 0.013) and per-protocol (30% versus 56%, P = 0.003) analyses. The numbers of both cardiopulmonary (7% versus 24%, P = 0.007) and tissue-healing complications (16% versus 31%, P = 0.04) were significantly reduced. No patients died in the restricted group compared with 4 deaths in the standard group (0% versus 4.7%, P = 0.12). No harmful adverse effects were observed.

Conclusion: The restricted perioperative intravenous fluid regimen aiming at unchanged body weight reduces complications after elective colorectal resection.

MYLES ET AL (2018)

This international trial randomly assigned 3000 patients who had an increased risk of complications while undergoing major abdominal surgery to receive a restrictive or liberal intravenous-fluid regimen during and up to 24 hours after surgery. The primary outcome was disability-free survival at 1 year. Key secondary outcomes were acute kidney injury at 30 days, renal-replacement therapy at 90 days, and a composite of septic complications, surgical-site infection, or death.

Results: Up to 24 hours after surgery, 1490 patients in the restrictive fluid group had a median intravenous-fluid intake of 3.7 liters, as compared with 6.1 liters in 1493 patients in the liberal fluid group. The rate of disability-free survival at 1 year was 81.9% in the restrictive fluid group and 82.3% in the liberal fluid group. The rate of AKI was 8.6% in the restrictive fluid group and 5.0% in the liberal fluid group. The rate of septic complications or death was 21.8% in the restrictive fluid group and 19.8% in the liberal fluid group; rates of surgical-site infection (16.5% vs. 13.6%) and renal-replacement therapy (0.9% vs. 0.3%) were higher in the restrictive fluid group, but the between-group difference was not significant after adjustment for multiple testing.

Conclusion: Among patients at increased risk for complications during major abdominal surgery, a restrictive fluid regimen was not associated with a higher rate of disability-free survival than a liberal fluid regimen and was associated with a higher rate of acute kidney injury.

Additional Reading: Romagnoli S, Ricci Z, Ronco C. Perioperative acute kidney injury: prevention, early recognition, and supportive measures. Nephron. 2018;140(2):105-110.

Salmasi V, et al. Relationship between intraoperative hypotension, defined by either reduction from baseline or absolute thresholds, and acute kidney and myocardial injury after noncardiac surgery: a retrospective cohort analysis. Anesthesiology. 2017;126:47-65. doi:10.1097/ALN.0000000000001432

OpenAnesthesia. Encyclopedia: Fluid Management. OpenAnesthesia. 2019. International Anesthesia Research Society. Retrieved from: http://www.openanesthesia.org/fluid-management/

EAST guidelines on the use of antibiotics in thoracostomy

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One discussion this week involved the use of antibiotics in thoracostomy.

Reference: Moore FO et al. Presumptive antibiotic use in tube thoracostomy for traumatic hemopneumothorax: An Eastern Association for the Surgery of Trauma practice management guideline. 2012. Retrieved from: https://www.east.org/education/practice-management-guidelines/tube-thoracostomy-presumptive-antibiotics-in

Summary:  A systematic review was done by 10 acute care surgeons and one statistician to update the 1998 guidelines for EAST. Routine presumptive antibiotic use to reduce the incidence of empyema and pneumonia in tube thoracostomy (TT) for traumatic hemopneumothorax is controversial. Moore et al (2012) conclude that there is insufficient published evidence to support any recommendation either for or against this practice. The authors further state that “until a large and likely multicenter, randomized, controlled trial can be performed, the routine practice of presumptive antibiotics in TT for chest trauma will remain controversial.”

Additionally, the authors are unable to recommend an optimal duration of antibiotic prophylaxis when antibiotics are administered for traumatic hemopneumothorax because there are insufficient published data to support the routine use of antibiotics.

Additional Reading: Department of Surgical Education, Orlando Regional Medical Center. Chest Tube Management. 2016 Sept 8. Retrieved from http://www.surgicalcriticalcare.net/Guidelines/Chest%20tube%20management%202016.pdf