Breast Reconstruction after Mastectomy

A number of studies have found that obesity significantly increases the risk of both flap and donor complications. A meta-analysis also demonstrated that muscle-sparing abdominal flaps resulted in a lower pooled incidence of flap loss and fat necrosis.

While radiation is associated with higher wound healing complications with reconstruction, the rate of complications is similar whether reconstruction precedes or follows radiation.

Complication rates of immediate autologous reconstruction are similar between those taking neoadjuvant chemotherapy and those who do not.

There are no significant differences in the rate of chest wall recurrence after mastectomy whether a skin-sparing procedure with immediate reconstruction is performed or not.

Kelley BP, Ahmed R, Kidewll KM, Kozlow JH, Chung KC, Momoh AO. A systematic review of morbidity associated with autologous breast reconstruction before and after exposure to radiotherapy: are current practices ideal? Ann Surg Oncol. 2014;21:1732-1738.

Lee KT and Mun GH. Effects of obesity on postoperative complications after breast reconstruction using free muscle-sparing transverse rectus abdominis myocutaneous, deep inferior epigastric perforator, and superficial inferior epigastric artery flap: A systematic review and meta-analysis. Ann Plast Surg. Epub ahead of print December 19, 2014; doi: 10.1097/SAP.0000000000000400.

Renal Disease and Hyperparathyroidism

Patients with hyperparathyroidism may develop kidney stones or nephrocalcinosis (deposition of calcium salts in the renal parenchyma). Over time, the renal effects may result in a decline in renal function. In some patients, the diagnosis of hyperparathyroidism is a direct result of a work-up in those initially presenting with calcium-containing stones. Read more at :https://arrangoizmd.com/2022/07/22/kidney-disease-and-hyperparathyroidism/

Treatment of Triple Negative Breast Cancer after Lumpectomy

The ideal margin width after mastectomy has been debated, but the definition of a negative margin for invasive cancer as used in the National Surgical Adjuvant Breast and Bowel Project (NSABP) trials and recommended in the recent SSO Consensus Panel was no invasive tumor at the inked margin. Other randomized trials did not specify margin status or used grossly negative.

A recent consensus conference sponsored by the SSO, ASTRO, and CAP reviewed the literature and concluded that no tumor on ink is an adequate margin for breast-conserving surgery and radiation.

Shave margins appear to be the most efficient way to examine margin status and determine need for reoperation.

The width of margins for ductal carcinoma in situ (DCIS) is more hotly debated.

A patient treated with BCS and a pathology report showing a T2N0(i+) breast malignancy that is triple negative should be evaluated in a multidisciplinary approach, so a medical oncologist and a radiation oncologist are important in the evaluation of this patient. Even if the patient chose to have mastectomy, a referral to a medical oncologist is indicated. Isolated tumor cells are not a reason to perform ALND.

ER(-) patients should not have Oncotype testing. Patients with node-negative, ER-positive cancer are the most likely to benefit from multigene expression-based prognostic tests. In contrast, adjuvant chemotherapy remains a standard recommendation for patients with T2N0 cancers that are ER-negative, PR-negative, and HER2-negative or are HER2-positive.

Several multigene prediction assays are commercially available (Oncotype Dx; Mammaprint, and PAM50), but only Oncotype Dx has level 1B evidence to support its use in predicting benefit of adjuvant chemotherapy. This genomic profile was tested using tumor tissue from patients treated on a randomized clinical trial comparing tamoxifen to tamoxifen plus chemotherapy. The other genomic assays provide good prognostic information but were not well validated. However, clinical trials are underway to validate each of these tests in randomized patient samples. The decision to order a multigene assay test is usually left to the medical oncologist to determine whether or not the test is indicated. If a patient is not willing to accept a recommendation of adjuvant chemotherapy, the information from the test will not be useful.

At times a surgeon can order the multigene assay so that the information is available to the oncologist at the time of the visit, but it is important that the surgeon and medical oncologist communicate as to which patients should have this test performed so that the information is useful to the patient and the multidisciplinary team.

Chagpar AB, Killelea BK, Tsangaris TN, et al. A randomized, controlled trial of cavity shave margins in breast cancer. N Engl J Med. 2015;373:503-510.

Gangi A, Chung A, Mirocha J, Liou DZ, Leong T, Giuliano AE. Breast-conserving therapy for triple-negative breast cancer. JAMA Surg. 2014;149:252-258.

Giuliano AE, Hawes D, Ballman KV, et al. Association of occult metastases in sentinel lymph nodes and bone marrow with survival among women with early-stage invasive breast cancer. JAMA. 2011;306:385-393.

Meattini I, Desideri I, Saieva C, et al. Impact of sentinel node tumor burden on outcome of invasive breast cancer patients. Eur J Surg Oncol. 2014;40:1195-1202.

Moran MS, Schnitt SJ, Giuliano AE, et al. Society of Surgical Oncology-American Society for Radiation Oncology consensus guideline on margins for breast-conserving surgery with whole-breast irradiation in Stages I and II invasive breast cancer. Ann Surg Oncol. 2014;21:704-716.

Lymphedema After Breast Surgery

A number of studies have found that lifting weights reduces the development of lymphedema.

It is also clear that air travel (whether long or short haul) does not increase the risk of lymphedema>

Sleeves are not indicated unless there is established lymphedema.

A Cochrane review found no increase in lymphedema associated with early shoulder-mobilization exercises (within 7 days of surgery), and in fact found that these were better than delayed exercises.

Weight loss, whether through reducing calories or fat intake, has been found to result in reduced lymphedema.

Studies have found that patients with a prior axillary dissection could undergo elective hand surgery (including carpal tunnel surgery) without an increase in lymphedema rates.

References:

Brown JC, Schmitz KH. Weight lifting and physical function among survivors of breast cancer: a post hoc analysis of a randomized controlled trial. J Clin Oncol. 2015;33:2184-2189.

Kilbreath SL, Ward LC, Lane K, et al. Effect of air travel on lymphedema risk in women with history of breast cancer. Breast Cancer Res Treat. 2010;120:649-654.

Stuiver MM, ten Tusscher MR, Agasi-Idenburg CS, Lucas C, Aaronson NK, Bossuyt PM. Conservative interventions for preventing clinically detectable upper limb lymphedema in patients who are at risk of developing lymphedema after breast cancer therapy. Cochrane Database Syst Rev. 2015;2:CD009765.

Randomized Controlled Study Comparing Efficacy and Toxicity of Weekly vs. 3-Weekly Induction Chemotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma

Background: Head and Neck Cancer is a major public health problem in India, majority of which are lifestyle related, male predominant requiring dedicated infrastructure and human resource. The 5-year survival is 59% for all stages combined and only 45% in patients with locally advanced inoperable head and neck cancer using current chemoradiation schedules. Chemotherapy agents administered in the induction or concurrent setting comprise of taxanes (Docetaxel, paclitaxel), platinum compounds (Cisplatin, carboplatin) and fluorouracil (TPF). For patients with advanced Head and neck squamous cell carcinoma (HNSCC), 3-weekly TPF regimen is the established standard induction chemotherapy (ICT) option based on overall survival benefit. However, TPF regimen is known to be associated with significant dose limiting toxicities which may impair tolerance and effectiveness of therapy. In this study we assessed the efficacy and toxicity of weekly vs. 3-weekly Docetaxel, Cisplatin, and Fluoro-uracil (TPF) induction chemotherapy in locally advanced Head and neck squamous cell carcinoma (LA-HNSCC).

Methods: This was an open labeled randomized two arm study with 41 patients in the 3-weekly TPF arm and 41 patients in the weekly arm. Patients were randomized using numbers from a randomization software, data recorded, and results were analyzed.

Results: The weekly group achieved far greater symptom relief than 3-weekly group (72 vs. 64%). The overall response rates were similar in both arms (ORR 75.6 and 73.1% in the weekly and 3-weekly groups, respectively). Renal toxicity was significantly lower in the weekly group as compared to 3 weekly arm post three cycles of chemotherapy (CrCl 91.49 ml/min vs. 76.67 ml/min, respectively). The weekly group had predominantly grade I and II neutropenia (19.5 and 17.1%, respectively) as compared to 3-weekly group where grade III and IV neutropenia (31 and 12%, respectively) was more prominent (p-0.003). Among non-hematological toxicities, mucositis, nausea/vomiting, and diarrhea in the weekly group were significantly lower when compared to 3-weekly group. Progression free survival was slightly higher in the weekly group (18 months) when compared to 3-weekly group (15 months) which was not statistically significant.

Conclusion: Weekly induction with TPF had lower toxicity and similar efficacy as compared to 3-weekly regimen in locally advanced HNSCC patients. Myelosuppression, which was the most serious and common complication of 3-weekly TPF regimens was notably low using the weekly regimen. Our results suggest that weekly TPF regimen may be a safer and effective alternative to 3-weekly TPF for treatment of LA-HNSCC. To our knowledge this is the first study reporting the efficacy of weekly TPF regimen in LA-HNSCC till date.

Induction chemotherapy with cisplatin and fluorouracil alone or in combination with docetaxel in locally advanced squamous-cell cancer of the head and neck: long-term results of the TAX 324 randomised phase 3 trial

Background

At a minimum follow-up of 2 years, the TAX 324 study showed a significant survival benefit of induction chemotherapy with docetaxel, cisplatin, and fluorouracil (TPF) versus cisplatin and fluorouracil (PF) in locally advanced head and neck cancer. We report the long-term results at 5 years’ minimum follow-up.

Methods

TAX 324 was a randomized, open-label phase 3 trial comparing three cycles of TPF induction chemotherapy (docetaxel 75 mg/m2, followed by intravenous cisplatin 100 mg/m2 and fluorouracil 1000 mg/m2 per day, administered as a continuous 24-h infusion for 4 days) with three cycles of PF (intravenous cisplatin 100 mg/m2, followed by fluorouracil 1000 mg/m2 per day as a continuous 24-hour infusion for 5 days) in patients with stage III or IV squamous-cell carcinoma of the head or neck. Both regimens were followed by seven weeks of chemoradiotherapy with concomitant weekly carboplatin. Randomization was done centrally with the use of a biased-coin minimization technique. At study entry, patients were stratified according to the site of the primary tumour, nodal status (N0 or N1 vs N2 or N3), and institution. For this long-term analysis, data as of Dec 1, 2008, were gathered retrospectively from patients’ medical records. Overall and progression-free survival were the primary endpoints. Tracheostomy and dependence on a gastric feeding tube were used as surrogate measures for treatment-related long-term toxicity. The intention-to-treat analysis included data from all 501 patients (255 TPF, 246 PF); data from the initial analysis in 2005 were used for 61 patients who were lost to follow-up. TAX 324 was registered at ClinicalTrials.gov, NCT00273546.

Findings

Median follow-up was 72·2 months (95% CI 68·8–75·5). Overall survival was significantly better after treatment with TPF versus PF (hazard ratio [HR] 0·74, 95% CI 0·58–0·94), with an estimated 5-year survival of 52% in patients treated with TPF and 42% in those receiving PF. Median survival was 70.6 months (95% CI 49·0–89·0) in the TPF group versus 34.8 months (22·6–48·0) in the PF group (p=0·014). Progression-free survival was also significantly better in patients treated with TPF (median 38.1 months, 95% CI 19·3–66·1, vs 13.2 months, 10·6–20·7; HR 0·75, 95% CI 0·60–0·94). They detected no significant difference in dependence on gastric feeding tubes and tracheostomies between treatment groups. In the TPF group, three (3%) of 91 patients remained feeding-tube dependent, compared with eight (11%) of 71 patients in the PF group. Six (7%) of 92 patients had tracheostomies in the TPF group, versus eight (11%) of 71 in the PF group.

Interpretation

Induction chemotherapy with TPF provides long-term survival benefit compared with PF in locally advanced head and neck cancer. Patients who are candidates for induction chemotherapy should be treated with TPF.

Cisplatin, Fluorouracil, and Docetaxel in Unresectable Head and Neck Cancer – TAX 323

The Head and Neck Cancer Group of the European Organization for Research and Treatment of Cancer (EORTC) conducted a phase 3 trial, called the EORTC 24971 / TAX 323 study

Background
Phase 2 studies suggest that the standard regimen of cisplatin and fluorouracil (PF) plus docetaxel (TPF) improves outcomes in squamous-cell carcinoma of the head and neck. They compared TPF with PF as induction chemotherapy in patients with locoregionally advanced, unresectable disease.

Methods
They randomly assigned eligible patients between the ages of 18 and 70 years who had stage III or stage IV disease and no distant metastases to receive either TPF (docetaxel and cisplatin, day 1; fluorouracil by continuous infusion, days 1 to 5) or PF every 3 weeks for four cycles. Patients without progression of disease received radiotherapy within 4 to 7 weeks after completing chemotherapy. The primary end point was progression-free survival.

The TPF regimen consisted of docetaxel at a dose of 75 mg per square meter, administered as a 1-hour infusion on day 1, fol- lowed by cisplatin at a dose of 75 mg per square meter, administered as a 1-hour infusion on day 1, and fluorouracil at a dose of 750 mg per square meter per day, administered by continuous infu- sion on days 1 to 5. The PF regimen consisted of cisplatin at a dose of 100 mg per square meter, administered as a 1-hour infusion on day 1, fol- lowed by fluorouracil at a dose of 1000 mg per square meter per day, administered by continu- ous infusion on days 1 to 5.

Results
A total of 358 patients underwent randomization, with 177 assigned to the TPF group and 181 to the PF group. At a median follow-up of 32.5 months, the median pro- gression-free survival was 11.0 months in the TPF group and 8.2 months in the PF group (hazard ratio for disease progression or death in the TPF group, 0.72; P=0.007). Treatment with TPF resulted in a reduction in the risk of death of 27% (P=0.02), with a median overall survival of 18.8 months, as compared with 14.5 months in the PF group. There were more grade 3 or 4 events of leukopenia and neutropenia in the TPF group and more grade 3 or 4 events of thrombocytopenia, nausea, vomiting, stomatitis, and hearing loss in the PF group. The rates of death from toxic effects were 2.3% in the TPF group and 5.5% in the PF group.

Conclusions
As compared with the standard regimen of cisplatin and fluorouracil, induction chemotherapy with the addition of docetaxel significantly improved progression- free and overall survival in patients with unresectable squamous-cell carcinoma of the head and neck. (ClinicalTrials.gov number, NCT00003888.)