Optimizing surgical strategy in locally advanced breast cancer: a comparative analysis between preoperative MRI and postoperative pathology after neoadjuvant chemotherapy.

PURPOSE: In the treatment of breast cancer, neo-adjuvant chemotherapy is often used as systemic treatment followed by tumor excision. In this context, planning the operation with regard to excision margins relies on tumor size measured by MRI. The actual tumor size can be determined through pathologic evaluation. The aim of this study is to investigate the correlation and agreement between pre-operative MRI and postoperative pathological evaluation. METHODS: One hundred and ninety-three breast cancer patients that underwent neo-adjuvant chemotherapy and subsequent breast surgery were retrospectively included between January 2013 and July 2016. Preoperative tumor diameters determined with MRI were compared with postoperative tumor diameters determined by pathological analysis. Spearman correlation and Bland-Altman agreement methods were used. Results were subjected to subgroup analysis based on histological subtype (ER, HER2, ductal, lobular). RESULTS: The correlation between tumor size at MRI and pathology was 0.63 for the whole group, 0.39 for subtype ER + /HER2-, 0.51 for ER + /HER2 + , 0.63 for ER-/HER2 +, and 0.85 for ER-/HER2-. The mean difference and limits of agreement (LoA) between tumor size measured MRI vs. pathological assessment was 4.6 mm (LoA -27.0-36.3 mm, n = 195). Mean differences and LoA for subtype ER + /HER2- was 7.6 mm (LoA -31.3-46.5 mm, n = 100), for ER + /HER2 + 0.9 mm (LoA -8.5-10.2 mm, n = 33), for ER-/HER2+ -1.2 mm (LoA -5.1-7.5 mm, n = 21), and for ER-/HER- -0.4 mm (LoA -8.6-7.7 mm, n = 41). CONCLUSION: HER2 + and ER-/HER2- tumor subtypes showed clear correlation and agreement between preoperative MRI and postoperative pathological assessment of tumor size. This suggests that MRI evaluation could be a suitable predictor to guide the surgical approach. Conversely, correlation and agreement for ER + /HER2- and lobular tumors was poor, evidenced by a difference in tumor size of up to 5 cm. Hence, we demonstrate that histological tumor subtype should be taken into account when planning breast conserving surgery after NAC.

Long-term quality of life and aesthetic outcomes after breast conserving surgery in patients with breast cancer.

INTRODUCTION: Breast surgery has become less invasive without compromising survival and aimed at improving quality of life (QoL) in terms of satisfaction with cosmesis. Despite that, short-term patient-perceived aesthetic results after breast-conserving surgery (BCS) can still be displeasing. Long-term analysis regarding contentment with cosmesis are lacking and could be different, considering that over time, patients' priorities might change and a different thought-out judgment could be given. The goal of this study is to describe long-term results in QoL after BCS and to identify possible predictors for disappointing aesthetic results. METHODS: In this retrospective cohort study, the long-term outcomes of QoL, patient-reported outcome measurements and aesthetic outcomes were investigated 4.5-10.8 years after BCS. In total, 104 patients received standardized questionnaires from the European Organisation of Research and Treatment of Cancer. The aesthetic results after BCS were evaluated subjectively through a diverse panel of healthcare observers. Objective assessment of the aesthetic results was done using the BCCT.core system of evaluating standardised breast photographs. Factors influencing aesthetic outcome were statistically analysed. RESULTS: QoL was high in around 75% of the patients. Correlation between QoL and aesthetic outcomes was found according to Spearman's correlation (r = 0.262, p = 0.007). Significant factors negatively influencing patient reported aesthetic outcomes were sentinel node procedure (p = 0.016), axillary lymph node dissection (p = 0.004), chemotherapy (p = 0.001), and hormonal therapy (p = 0.001). CONCLUSION: The majority of the patients have acceptable QoL after BCS during long-term follow-up. Unacceptable aesthetic outcomes after BCS are associated with lower QoL and are influenced by sentinel node procedure, axillary lymph node dissection, chemotherapy, and hormonal therapy.

Ultrasound-guided breast-conserving surgery for early-stage palpable and nonpalpable invasive breast cancer: decreased excision volume at unchanged tumor-free resection margin.

Ultrasound guidance (USG) during breast-conserving surgery improves tumor-free surgical resection margins. The objective of this study was to evaluate whether USG reduces resection volumes without compromising margin status. 134 patients with palpable or nonpalpable T1-2N0-1 invasive breast cancer were treated with USG and compared with a historical reference control group (CON) consisting of palpation-guided (PAG) or wire-guided localization (WIG) breast-conserving surgery. Primary outcomes were excess resection volume and clear margin status, and secondary outcome was re-excision rate. 66 patients underwent USG. In the CON group (n = 68), PAG was performed in 24 (35 %) and WIG in 44 (64 %) patients. Median excision volume [39 (IQR 20-66) vs 56 (38-94) cm(3); p = 0.001] and median calculated resection ratio [1.7 (1.0-2.9) vs 2.8 (1.4-4.6) (p = 0.005)] were significantly smaller in the USG than in the CON group. Median minimal distance to the resection margin [4 mm (IQR 2-5 mm) vs 2 mm (1-4 mm), p = 0.004] was significantly larger. Clear resection margins were achieved in 58 of the USG patients (88 %) and in 58 of the CON patients (86 %) (p = 0.91); this was true in patients with palpable as well as nonpalpable lesions. Reexcision was needed in 6.1 and 7.2 % respectively. Relative risk for re-excision in the USG group was 0.82 (95 % CI 0.23-2.93). In patients with palpable and nonpalpable breast cancers, USG allows for lower excision volume and reduced resection of healthy breast tissue, without increased re-excision rate.

The health-related quality of life of long-term survivors of melanoma treated with isolated limb perfusion.

AIMS: To evaluate the generic and condition-specific health-related quality of life (HRQL) of long-term survivors of extremity melanoma treated with isolated limb perfusion (ILP). METHODS: Between 1978 and 2001, 292 patients with melanoma of the limbs underwent ILP in our institution. Of these patients, 59 were alive and disease-free for at least six months prior to study entry. Fifty-one of these 59 patients completed a mailed questionnaire assessing generic HRQL (SF-36), condition-specific HRQL (limb function, cosmetic results, fear of recurrence), and problems regarding work and insurance. An age- and gender-matched, normative sample of the Dutch general population was available for comparison of SF-36 scores. RESULTS: Mean age of patients was 57 years, 90% female, with a median time since ILP of 14 years (range 3-25 years). The SF-36 scores of the patient group were equal to or better than that of the general population, significantly for bodily pain, general health perceptions, and the physical and mental health component scores. Nevertheless, the patients reported a number of specific problems: complaints of limb function were reported by 49-55%, cosmetic problems by 31-38% and fear of local disease recurrence and distant metastases by 77 and 63% of the patients, respectively. Less than 10% of patients reported problems in obtaining a mortgage or life insurance. CONCLUSIONS: The HRQL of long-term survivors of melanoma treated with ILP appears comparable to, and sometimes better than that of healthy peers within the general population. Nevertheless, this survivor group reports a number of specific problems that impact on daily life. Although these findings need to be confirmed with larger, prospective studies, they suggest that rehabilitation should focus on improving limb functionality, and addressing chronic fear of disease recurrence.

Repeat isolated limb perfusion with TNFalpha and melphalan for recurrent limb melanoma after failure of previous perfusion.

AIM: To assess the effectiveness of isolated limb perfusion (ILP) with tumour necrosis factor-alpha (TNFalpha) and melphalan for recurrent or persistent melanoma lesions after previous ILP. METHODS: Between 1978 and 2001, 21 patients (mean age 65, range 29-83 years) underwent repeat ILP for recurrent or persistent melanoma after a previous ILP. First ILPs had been performed with melphalan alone in 13 patients and with addition of TNFalpha in eight, for a median of nine lesions (interquartile (IQ) range 2-23 lesions). Repeat ILP was performed with TNFalpha and melphalan in all 21 patients for a median of nine lesions (IQ range 5-25 lesions). Median follow-up after repeat ILP was 18 months (IQ range 6-36 months). RESULTS: Thirteen patients attained a complete response (CR) after repeat ILP compared to 11 of 17 with measurable lesions after the first ILP. Nine patients relapsed after CR. Median limb recurrence-free survival was 13 months. Fourteen patients had mild acute regional toxicity after repeat ILP compared to 18 after the first ILP (n.s.). One patient underwent amputation for critical limb ischemia 10 months following repeat ILP. The limb salvage rate was 95%. Overall median survival was 62 months after CR compared to 13 months for those without CR (P=0.05). CONCLUSION: Repeat ILP with TNFalpha and melphalan is feasible after previous ILP with mild regional toxicity. The CR rate is relatively high and comparable to the first procedure with good limb recurrence-free survival and high limb salvage rate.

Palliative isolated limb perfusion for advanced limb disease in stage IV melanoma patients.

INTRODUCTION: Two to three percent of the patients with extremity melanoma develop in-transit metastases in the course of their disease. When local treatments fail, isolated limb perfusion (ILP) is a reasonable option, but is generally only applied to patients without evidence of distant metastases. We assessed the value of ILP in stage IV melanoma patients with symptomatic unresectable limb melanoma at our institutions. PATIENTS AND METHODS: A computerized database, containing all patient, tumor, ILP, and follow-up data of 505 ILPs performed in 451 patients between 1978 and 2001, allowed the selection of eight (1.8%) stage IV patients who underwent a palliative ILP for unresectable melanoma lesions on the limbs. All patients had high tumor burden limb disease, according to the combined Fraker and Rossi criteria. RESULTS: The overall tumor response rate was 88%, with 13% complete and 75% partial response rates. One patient did not respond to ILP. Three partial responding patients attained a complete remission (CR) after excision of the remaining limb lesions. The median duration of hospital stay was 12 days and acute regional toxicity was mild with slight erythema and edema in six and no signs of reaction in two patients. The median limb recurrence-free interval after CR was 6 months and the median duration from the time of distant metastases to death was 15 months. Overall ILP leads to the desired palliative effect in six patients (75%). CONCLUSION: ILP should be considered as a palliative treatment in selected stage IV melanoma patients with symptomatic advanced limb disease.

Major amputation for intractable extremity melanoma after failure of isolated limb perfusion.

AIM: The aim of this study was to analyse indications and results of amputation for intractable extremity melanoma after failure of isolated limb perfusion (ILP). METHODS: Between 1978 and 2001, 451 patients with loco-regional advanced extremity melanoma underwent 505 ILPs. Amputation of the affected extremity had to be carried out for intractable recurrent disease in 11 of these patients. RESULTS: The indications for amputation were uncontrollable pain (n=2), extensive loco-regional tumour progression (n=4), loss of ankle function due to local tumour growth (n=1), and ulcerating and fungating lesions, not responding to other treatments (n=4). Four patients developed stump recurrence after amputation. Ten patients died of melanoma metastases after a median of 11 months (range 2-110 months). Two patients survived more than 5 years after amputation. CONCLUSIONS: Major amputation is rarely indicated for intractable extremity melanoma but long-term survival can be achieved in selected patients.

Prognostic factors for survival after isolated limb perfusion for malignant melanoma.

AIMS: Risk factors were determined for mortality within 1 year after isolated limb perfusion (ILP). METHODS: All of 439 patients who underwent ILP for melanoma of the extremities were studied. Ninety percent of the patients had MD Anderson stage IIB or III disease at the time of ILP. ILP was performed with melphalan with or without TNFalpha under mild hyperthermic (38-40 degrees C) or normothermic (37-38 degrees C) conditions in 80% of the cases. RESULTS: Sixty-nine patients died within this period, 64 of metastatic melanoma. The indication for ILP was an unresectable primary (n=3), a local recurrence (n=24) or adjuvant to excision of primary lesions (n=17) in patients with stage IIIB regional lymph node metastases. These patients or patients with stage IIIAB melanoma with satellites and/or in-transit metastases with regional lymph node metastases had a relative risk of 4.6 (95% CI 2.0-6.6) and 3.6 (95% CI 2.1-10) of dying within 1 year from ILP, respectively (p<0.001). In patients with stage IV disease (distant metastases), the relative risk was 22 (95% CI 3.8-127, p=0.001). CONCLUSION: Patients with advanced limb melanoma have an increased risk of death within 1 year after ILP when regional lymph node or distant metastases are present.

[Regional isolated perfusion: also applicable in elderly patients]. / Regionale isolatieperfusie: ook bij bejaarde patiënten goed toepasbaar.

In 3 patients over 75 years of age with a malignancy, limb salvage was achieved through the application of isolated limb perfusion with melphalan with or without tumour necrosis factor alpha: an 82-year-old woman with extensive locoregional melanoma metastases on her lower leg, a 78-year-old woman with a large, ulcerating recurrence of melanoma on her lower leg and an 83-year-old woman with recurrent sarcoma of the lower arm. There were no complications and the women recovered well. Isolated limb perfusion can be effectively and safely used in older patients with irresectable tumours of the extremities, offering them limb salvage for the remainder of their lives.

Safety and efficacy of isolated limb perfusion in elderly melanoma patients.

BACKGROUND: Older patients are assumed to have a higher risk of complications from isolated limb perfusion (ILP). A study was performed evaluating the safety and efficacy of ILP in patients older than 75 years with advanced melanoma of the limbs. METHODS: A total of 218 therapeutic ILPs with melphalan with or without tumor necrosis factor alpha were performed in 202 patients with advanced measurable melanoma and were analyzed retrospectively. Fifty-three patients (28%) were 75 years or older. RESULTS: Complete response rates were 56% for those older than 75 years and 58% for the younger group (P =.79). Locoregional relapse occurred in 56% of the older group versus 51% in the younger group (P =.61). Limb toxicity, systemic toxicity, local complications, and long-term morbidity were similar in both age groups. Perioperative mortality was low, with one procedure-related death in the older group. Older patients stayed in the hospital for a median of 23 days (younger patients, 19 days; P <.01). CONCLUSIONS: ILP results in similar response rates in the elderly with recurrent melanoma, without increased toxicity, complications, or long-term morbidity compared with younger patients. Older age in itself is not a contraindication for ILP.

Isolated limb perfusion with melphalan for femoral metastases of breast cancer: case report.

BACKGROUND AND OBJECTIVES: Complications of bone destruction occur in 10-29% of breast cancer patients with skeletal metastases. Palliative treatment consists of systemic chemotherapy, hormonal treatment, radiotherapy, and/or surgery in the case of (impending) fracture. A case is presented where isolated limb perfusion was applied for this indication. METHODS: A 43-year-old woman with extensive femoral metastases of breast cancer with impending fracture was treated with isolated limb perfusion (ILP) with melphalan. Radiotherapy had resulted only in pain reduction, and intramedullary fixation was opted against because stable fixation was considered not feasible due to the location of the metastases. ILP with high-dose melphalan (10-20 times the amount that can be administered systemically) under normothermic (37-38 degrees C) conditions, resulted in partial remission and reossification. RESULTS: One year after ILP, until her death 2 years later, due to progressive metastases at other sites, the patient was able to bear weight again on her left leg. CONCLUSIONS: In selected patients with symptomatic large bone metastases from breast cancer, and no other treatment options, ILP with melphalan may be used for successful palliation.

Adult height and age at menarche in childhood cancer survivors.

The aim of this study was to assess the long-term effects of cancer treatments on adult height and age at menarche in survivors of various types of childhood cancer. 285 childhood cancer survivors (161 men and 124 women), at least 18 years old and having been off treatment for at least 5 years, were examined. The effects of cranial (CrRT) and craniospinal irradiation (CrSpRT), other treatments and age at diagnosis on adult height and age at menarche were investigated. Patients who did not receive CrRT or CrSpRT, reached normal adult heights. However, a significant reduction in adult height was observed in men and women treated with CrRT or CrSpRT, especially if the treatment was given at the age of 8 years or younger. In girls, CrRT resulted in a significantly earlier menarche, compared with the Dutch population. Chemotherapy, radiation dose and age at menarche did not affect adult height. The relative risk (RR) of attaining an adult height below the 3rd percentile (20% 49/244) of the study population) was 6 times increased (RR=6.4; 95% confidence interval (CI) 1.46-28.52) after CrSpRT, 4 times (RR=4.2; 95% CI 1.81-9.63) after Crth and 5 times (RR=51; 95% CI 2.23-11.59) when irradiation was administered at the age of 8 years or younger. CrRT and CrSpRT and age at treatment are the main determinants of short stature in male and female childhood cancer survivors.