Management of the axilla in breast cancer patients: critical review, regional modified Delphi consensus and implementation in the Tuscan breast network.

PURPOSE: Data from recently trials have provided practice-changing recommendations in management of the axilla in early breast cancer (eBC). However, further controversies have been raised, resulting in heterogeneous diffusion of these recommendations. Our purpose was to obtain a better homogeneity. MATERIAL AND METHODS: In 2021, the Tuscan Breast Network (TBN) established a consensus with the aim to update recommendations in this area. We performed a literature review on axillary management in eBC patients which led to an expert Delphi consensus aiming to explore the gray areas, build consensus and propose evidence-based suggestions for an appropriate management. Thereafter, we investigate their implementation in clinical practice. RESULTS: (1) DCIS patients should have SLN biopsy only in case of mastectomy or in conservative surgery if tumor is in a location that would preclude future nodal sampling or in case of a mass; (2) ALND may be omitted for 1-2 positive SLN patients undergoing BCS in T1-2 tumors with 1-2 SLN positive, eligible for whole-breast irradiation and adjuvant systemic therapies; (3) consider the option of RNI in patients with 1-3 positive lymph nodes and one or more high-risk characteristics; (4) the population identified in 2) should NOT undergo lymph node irradiation as an alternative to axillary surgery and (5) patients with clinically (pre-operatively) positive axilla, or undergoing primary systemic therapy, or outside the criteria reported in 2) must receive additional ALND and/or RT as per local policy. CONCLUSION: This consensus provided a practical tool to stimulate local and national breast surgical and radiotherapy protocols.

Assessing psychological needs in female cancer patients: a tailored model.

BACKGROUND AND AIM OF THE WORK: Psychosocial needs in cancer patients seem to be underestimated and undertreated. The present research was designed to explore under-considered psychosocial needs (e.g., stressful life events, perceived social support, sense of mastery and depressive/anxious symptoms) of a female cancer group. The aim of the study was to test an assessment psycho-oncological model for female cancer patients. An assessment model of psychosocial needs and Stressful Life Events was operationalized and tests its predictive power. METHODS: We used Discriminant Analysis to test predictive power of the model and of the single variables included in it. 236 oncological patients (mean age 55.50 ± 13.09) were matched with 232 healthy control groups in the study. The following instruments were chosen: the Florence Psychiatric Interview, Hospital Anxiety Depression Scale, Multidimensional Scale of Perceived Social Support, Beck Depression Inventory I, and Sense of Mastery. RESULTS: The model satisfied the assumption criteria and was significant (Ʌ= .680, X2 = 109.73, p< .001). CONCLUSIONS: Stressful events, depression and anxiety were adequate markers of the assessment psycho-oncological model proposed for female cancer patients. The present study provides contributions in a clinical perspective: the results support the relevance of considering an assessment psychosocial model to use in female oncology for an accurate estimation of the women's needs. Women affected by female cancer with an history of Stressful Early and Recent life events and high level of anxiety and depression could positively benefit from a psychotherapy treatment.

Identification of a Gene Panel for Endometrioid Endometrial Cancer: a Possible Prognostic Value?

The incidence of endometrial cancer (EC) is increasing in developed countries. The most frequent is the endometrioid subtype with usually good prognosis; nevertheless, some cases escape this paradigm and may have recurrence. A recent study from The Cancer Genome Atlas suggested to implement the EC analysis by molecular profile for improving diagnosis, prognosis, and therapeutic treatment. The present preliminary study was performed on 15 G3 endometrioid endometrial cancers (G3 EEC) for the identification of somatic mutations in a panel of specific exons in selected genes as ARID1A, CTNNB1, KRAS, PIK3CA, POLE, PTEN, and TP53. The combined procedure, based on the Sanger sequencing and PCR-high-resolution melting analysis, allowed the identification of variations of the selected gene panel in most of patients (93%) of our cohort. The overall evaluation of mutational load exhibited that the most frequent mutated genes were PTEN (93%), followed by PIK3CA (47%) suggesting a deep involvement of PI3K pathway alteration in G3 EEC. Mutations in TP53 (27%), ARID1A (27%), POLE (13%), and at the lower level in KRAS and CTNNB1 (7%) were also observed (exclusively in FIGO III stage patients). The evaluation of the mutations of our proposed panel (ARID1A, CTNNB1, KRAS, PIK3CA, POLE, PTEN, TP53) is suitable to improve the characterization of G3 EEC and could suggest targetable pathways for development of personalized treatments.

Use of Electronic Administrative Databases to Measure Quality Indicators of Breast Cancer Care: Experience of Five Regional Oncology Networks in Italy.

PURPOSE: Assuring quality of care, while maintaining sustainability, in complex conditions such as breast cancer (BC) is an important challenge for health systems. Here, we describe a methodology to define a set of quality indicators, assess their computability from administrative data, and apply them to a large cohort of BC cases. MATERIALS AND METHODS: Clinical professionals from the Italian Regional Oncology Networks identified 46 clinically relevant indicators of BC care; 22 were potentially computable using administrative data. Incident cases of BC diagnosed in 2016 in five Italian regions were identified using administrative databases from regional repositories. Each indicator was calculated through record linkage of anonymized individual data. RESULTS: A total of 15,342 incident BC cases were identified. Nine indicators were actually computable from administrative data (two structure and seven process indicators). Although most indicators were consistent with guidelines, for one indicator (blood tumor markers in the year after surgery, 44.2% to 64.5%; benchmark ≤ 20%), deviation was evident throughout the five regions, highlighting systematic overlooking of clinical recommendations. Two indicators (radiotherapy within 4 months after surgery if no adjuvant chemotherapy; 42% to 83.8%; benchmark ≥ 90%; and mammography 6 to 18 months after surgery, 55.1% to 72.6%; benchmark ≥ 90%) showed great regional variability and were lower than expected, possibly as result of an underestimation in indicator calculation by administrative data. CONCLUSION: Despite highlighting some limitations in the use of administrative data to measure health care performance, this study shows that evaluating the quality of BC care at a population level is possible and potentially useful for guiding quality improvement interventions.

Trabectedin in combination with pegylated liposomal doxorubicin in patients with ovarian tumors.

The majority of patients with ovarian cancer will experience relapse and thus require second-line therapy. While platinum-based therapies are the primary treatments for refractory disease other options are required, particularly for those with partially platinum-sensitive disease as their response rates are lower. Agents that can resensitize relapsed ovarian cancers to platinum, including trabectedin, are therefore of increasing interest. Trabectedin is a multitarget agent that has a complex, novel mechanism of action and has exhibited promising results in platinum-sensitive ovarian cancer when in combination with pegylated liposomal doxorubicin (PLD). The present study conducted retrospective analysis involving 11 cases (median age 60 years; range 45-75 years) of recurrent ovarian tumors and partial platinum sensitivity undergoing treatment with trabectedin + PLD. The cohort consisted of 7 serous carcinomas, 1 endometrial carcinoma, 2 undifferentiated carcinomas, and 1 mucinous carcinoma. Of the 11 patients, 4 exhibited a complete response, 3 achieved stable disease, and 4 had progression of disease. Mean overall survival was 32.42 months and median progression-free survival was 5.9 months. Trabectedin in combination with PLD was well tolerated in terms of gastrointestinal and hematological toxicity; Grade 3 cutaneous toxicity and grade 3 neutropenia were each observed in 18.2% of patients. There were no grade 4 events. Thus, the present study supports the use of trabectedin + PLD in patients with relapsed ovarian cancer and partial platinum sensitivity, with predictable and manageable toxicity.

Stable disease in a patient with metastatic leiomyosarcoma treated with trabectedin.

Leiomyosarcomas represent the most common variant of uterine sarcomas, and are also considered to be the least chemosensitive. To date, adriamycin and ifosfamide are believed to be the most effective drugs for its treatment, in addition to docetaxel and gemcitabine. Recently, the introduction of trabectedin has provided clinicians with another treatment option, and the drug may have some benefits for patients as it may allow for long-term treatment. We present the case of a patient who previously failed multiple cycles of chemotherapy and who was subsequently treated with 30 cycles of trabectedin as third-line therapy for multiple metastases of uterine leiomyosarcoma. During the treatment period, the dosage and dose interval of trabectedin were optimized because of the appearance of grade 4 hematological and gastrointestinal toxicity. Dose adjustments led to acceptable tolerability. Trabectedin was associated with a very good partial response, especially at the pulmonary and pancreatic levels, and stable disease was achieved at all metastatic sites. The patient is currently continuing treatment with trabectedin and has clinically stable disease after 2 years of therapy. This case report provides further evidence that trabectedin is a valid and well-tolerated therapeutic option that can be used in the long term in uterine leiomyosarcoma.

Participation and risk of high grade cytological lesions among immigrants and Italian-born women in an organized cervical cancer screening program in Central Italy.

Few studies analyzed the risk for high-grade squamous intraepithelial lesions or worse (HSIL+) among immigrants and natives attending organized cervical cancer (CC) screening programs (SP). We evaluated participation and diagnosis of HSIL+ by country of birth with logistic models. Overall 540,779 invitation letters were delivered to target women of Florence SP in three screening rounds (years 2000-2002, 2003-2005, 2006-2008). The probability of attending screening was lower for immigrants than natives, but the difference decreased from 35% (1st round) to 20% (2nd-3rd round) for women born in high migration pressure (HMP) countries. The risk of HSIL+ was double than natives for HMP-born women from countries with high prevalence of human papillomavirus, even adjusting for age and previous history of Pap test. This is an important public health problem due to an increasing proportion over time of immigrant women with a lower attendance and greater risk for CC.

Indicators of the standard of care for melanoma: Tuscany data.

Formal indicators for the evaluation of the quality of melanoma care are needed. We identified 13 process indicators, which encompassed early diagnosis, pathology reporting and surgical treatment. We evaluated the adherence to these indicators using a population-based series on incident skin melanomas (only primary melanomas) for the year 2004 (687 cases) and for the first semester of 2008 (539 cases). We compared the indicators for these 2 years. The melanoma incidence increased between 2004 and 2008. There were statistically significant increases in the percentage of thin (≤1 mm) melanomas (from 50.7 to 61.3%) and in the number of pathology reports that mentioned ulceration (from 61.4 to 84.6%) and margin status (from 76.8 to 84.3%). The percentage of patients staged by sentinel lymph node biopsy was stable (63%) and was higher for patients younger than 75 years of age (74%). The number of nodes almost invariably exceeded the proposed site-specific cutoff reference and, in 2008, the number of nodes removed was always reported for lymphadenectomy. From 2004 to 2008, surgical and pathological waiting times increased. Collection and analysis of these indicators would enable continuous evaluation of the quality of melanoma care in Tuscany and provide sources for a comparative study between Italy and elsewhere.

Feasibility of evaluating quality cancer care using registry data and electronic health records: a population-based study.

OBJECTIVE: To evaluate the quality of patients care, a set of indicators of the standards of cancer care were defined. PARTICIPANTS: We developed a set of indicators to assess the implementation in daily practice of recommendation produced by a regional network (Istituto Toscano Tumori). This set was tested in a retrospective study in the resident population of the Tuscany Region; the regional health system is organized on 12 local health authorities which refer to three macro areas (Area Vasta). The study included incident colorectal, lung and breast cancer cases listed in 2004 for the Tuscan Cancer Registry, a population-based registry which collected tumor cases diagnosed in all residents in Tuscany. Electronic data from registry database were used to determine the compliance with each indicator for patients in 2004. To validate the results, an ad hoc clinical survey including the same geographical area for the year 2006 was performed. INTERVENTION: None. MAIN OUTCOME MEASURES: The proportion of patients who fulfilled each of the indicators. RESULTS: Our study showed the feasibility of the evaluation of the quality of cancer care using cancer registry population-based data and major computerized information systems. The estimation of the selected indicators confirmed a good homogeneity among areas, and globally revealed a good intraregional performance. CONCLUSIONS: Further work is needed to develop specific quality measures, particularly about structural data and to continually revise indicators of quality of care. Data from a cancer registry, however, can be useful to evaluate quality of cancer care.

DNA ploidy is stronger than lymph node metastasis as prognostic factor in cervical carcinoma: 10-year results of a prospective study.

INTRODUCTION: To improve the outcome of patients with cervical cancer, a more accurate prognostic assessment is essential. The aim of this study was to evaluate the role of tumor DNA ploidy as an independent prognostic factor in cervical carcinoma. Furthermore, we investigated whether the presence of lymph node metastasis may have a different clinical impact according to ploidy status. METHODS: In a long-term prospective study, DNA ploidy was evaluated by flow cytometry from fresh tumor samples from 136 patients with cervical cancer who underwent surgery. Ploidy, lymph node metastasis, and other classical parameters were analyzed in relation to the length of disease-specific survival. Treatment modalities did not differ between patients with diploid tumors and patients with aneuploid tumors. RESULTS: DNA aneuploidy was found in 52 patients (38.2%). Patients with DNA-aneuploid tumors had a significantly reduced disease-specific survival (P = 0.003). Overall, the 10-year survival probability was 54% for patients with DNA-aneuploid tumors and 80% for patients with DNA-diploid tumors. Among 64 patients with International Federation of Gynecologists and Obstetricians stage I disease, the 10-year survival rates were 38.7% for the patients with DNA-aneuploid tumors and 86.3% for those with DNA-diploid tumors (P = 0.003). Overall, diploid tumors with lymph node metastasis did significantly better than aneuploid tumors with lymph node metastasis (P = 0.05). Among the patients with International Federation of Gynecologists and Obstetricians stage I disease, there was a highly significant difference between patients with diploid node-positive tumors and patients with aneuploid node-positive tumors, with no deaths from the disease in the former group in contrast with the worst outcome in the latter group (P = 0.005). By multivariate analysis, pathologic tumor stage, lymph vascular invasion, and tumor ploidy were significant and independent parameters, whereas lymph node metastasis yielded no independent information. CONCLUSIONS: DNA ploidy was an independent prognostic factor in cervical carcinoma. Presence of lymph node metastasis may not always have the same impact on survival but may vary according to DNA ploidy of the primary tumor.