Neoadjuvant endocrine therapy with or without palbociclib in low-risk patients: a phase III randomized double-blind SAFIA trial.

BACKGROUND: The most prevalent subtype of breast cancer (BC) is luminal hormonal-positive breast cancer. The neoadjuvant chemotherapy regimens have side effects, emphasizing the need to identify new startegies. OBJECTIVE: Analyze the complete pathologic response (pCR) rate and overall response in a low-risk hormone-positive subset of patients receiving neoadjuvant hormone treatment (NAHT) with or without Palbociclib (a CDK4/CDK6 inhibitor) to boost NAHT effectiveness. MATERIALS AND METHODS: Based on the upfront 21-gene Oncotype DX or low-risk Breast Recurrence Score assay (RS™), the SAFIA trial is designed as a prospective multicenter international, double-blind neoadjuvant phase-III trial that selects operable with luminal BC patients that are HER2-negative for the induction hormonal therapy with Fulvestrant 500 mg ± Goserelin (F/G) followed by randomization of responding patients to palbociclib versus placebo. The pCR rate served as the study's main outcome, while the secondary endpoint was a clinical benefit. RESULTS: Of the 354 patients enrolled, 253 initially responded and were randomized to either F/G fulvestrant with palbociclib or placebo. Two hundred twenty-nine were eligible for the evaluation of the pathologic response. No statistically significant changes were observed in the pCR rates for the patients treated with the F/G therapy with placebo or palbociclib (7% versus 2%, respectively) per the Chevallier classification (Class1 + Class2) (p = 0.1464) and 3% versus 10% assessed per Sataloff Classification (TA, NA/NB) (p = 0.3108). Palbociclib did not increase the rate of complete pathological response. CONCLUSION: Neoadjuvant hormonal therapy is feasible in a selected population with a low RS score of < 31 CLINICAL TRIAL: NCT03447132.

Therapeutic results and prognostic factors of stage III NSCLC: a population-based study in Tunisia.

BACKGROUND: Prognostic factors are crucial to guide patient's selection through therapeutic decisions and outcome prediction. AIM: To investigate prognostic factors associated with improved survival in stage III non-small cell lung cancer. PATIENTS AND METHODS: We retrospectively reviewed clinical data of 88 stage III non-small cell lung cancer patients treated between 2010-2017. Multidisciplinary evaluation prior to therapy onset was mandatory. Univariate analyses and multivariate logistic regression were performed to identify factors associated with survival. RESULTS: Median follow-up was 28 months, 56% of patients experienced recurrence. Median overall survival (OS) was 19 months. On univariable analysis, improved OS correlated with younger age (p = 0.011), better performance score (ECOG PS < 2) (p < 0.01), absence of weight loss (p = 0.019) and smaller tumor size (≤ 7 cm) (p = 0.005). OS was improved in patients receiving therapy planned by multidisciplinary meeting compared with those who did not (p < 0.01), in those with resected tumors (p = 0.001), responding to therapy (neoadjuvant chemotherapy (p = 0.034) and concurrent chemoradiation (p = 0.001), as well as those with lower neutrophil-lymphocyte ratio (p = 0.026) and lower platelet-lymphocyte ratio (p = 0.003). Postoperative adjuvant therapy increased OS (64 vs 24, p = 0.025). Longer recurrence-free interval, locoregional failure and better perfomance status at recurrence were good prognostic factors for OS. Multivariate analysis showed that only upfront surgery followed by adjuvant therapy (hazard ratio (HR) = 0.61; 95% confidence interval (CI) 0.38-0.96; p = 0.034), adherence to multidisciplinary team decision (HR = 0.26; 95% CI 0.15-0.47; p < 0.01) and tumor size > 7 cm (HR = 2.31; 95% CI 1.29-4.13; p = 0.005) were independent prognostic factors affecting OS. CONCLUSIONS: Optimal therapeutic strategy and adherence to the decision provided by the multidisciplinary evaluation of patients played an important role in stage III non-small cell lung cancer outcome.

[Diagnostic and therapeutic management of operable bronchopulmonary carcinoid tumours]. / Prise en charge diagnostique et thérapeutique des tumeurs carcinoïdes broncho-pulmonaires opérables.

INTRODUCTION: Bronchial carcinoid tumours (CT), divided into typical carcinoid (TC) or atypical carcinoid (AC), are rare tumours whose therapeutic management remains unspecified. METHODS: Retrospective study collecting cases of bronchial CT operated at the thoracic surgery department of Abderrahmane-Mami hospital of Ariana and recruited from the pneumology departments of Northern Tunisia, during a 12-year period. RESULTS: Ninety patients were collected (74 cases of TC and 16 cases of AC). The mean age was 45 years and the sex ratio H/F=0.5. The chest X-ray was normal in 11 cases, as well as flexible bronchoscopy in seven cases. The tumour was classified: stage IA (10 cases), IIA (28 cases), IIB (31 cases), IIIA (15 cases) and IIIB (six cases). Surgery resulted in a complete resection in 78 patients, an extensive resection in six patients, and a conservative resection in six patients. Adjuvant chemotherapy was given in 10 patients. The survival was 84% at five years and 42% at 10 years. CONCLUSION: The prognosis of CT depends directly on the histological subtype. It is excellent for TC after complete resection, unlike ACs that are similar to well-differentiated bronchial carcinomas.

Objective Clinical and Radiological Response under Sunitinib in a Case of Thigh Hidradenocarcinoma.

A 56-year-old male was treated by local surgery in 1968 and 2005 for a left thigh lesion. A 2nd local relapse occurred in 2015 and was treated by complete macroscopic surgery with histology concluding to a hidradenocarcinoma. A 3rd locoregional relapse occurred in October 2018, with the presence of inflammatory ulcerated lesions. A 2nd histology and immunohistochemistry exam showed a proliferation positive for CK, CK5, and p63 suggesting the diagnosis of hidradenocarcinoma. The patient was treated by 3 lines of chemotherapy, 1st by Adriamycin, 2nd by carboplatin-paclitaxel, and then 3rd by oral capecitabine, leading to a stable clinical disease but without a clinical benefit. A locoregional plus metastatic lung progression was observed in March 2019, with the presence of lung nodules and retroperitoneal lymph nodes, multiple skin left thigh and left inguinal ulcerated lesions. The patient received then in 4th line in April 2019 oral sunitinib at 50 mg daily, with 4 weeks therapy/2 weeks pause. Side effects were represented by mucositis, anorexia, weight loss, and fatigue. We observed since the 1st week of therapy a fast response, with a decrease of the ulcerated lesions, a skin loss, and deep hemorrhagic areas. CT-scan showed after 2 weeks of sunitinib an objective response on both locoregional and metastatic lesions.

Annual hazard rate of relapse of stage II and III colorectal cancer after primary therapy

Purpose. To report the annual hazard of relapse in stages II and III colorectal cancer (CRC) Tunisian patients treated with curative intent. We also aim to evaluate impact of oxaliplatine according to anatomo-clinical features. Methods. We collected data about clinico-pathological parameters of 331 CRCs. We analyzed annual hazard of recurrence (locoregional and/or distant) of the overall population and several subgroups: colon cancer vs rectal cancer and stage II vs stage III. We also analyzed impact of adjuvant oxaliplatine on recurrence within these subgroups. Results. Relapse rate was 38.1%, with a mean time to relapse of 27.6 months. We noted 23.8% local recurrence, 69.8% distant recurrence, and 6.4% both. We observed higher local relapse rate in rectal cancer (26.8 vs 3.2%) vs colon cancer (p = 0.004). Stage III had a higher metastatic relapse rate vs stage II (31.6 vs 20.8%, p = 0.043). Annual hazard of recurrence for the overall population showed two peaks: [1-2] year-interval by 10.1% and [3-4] year-interval by 11.3%. Stage III showed significantly higher and earlier recurrence hazard peak compared to stage II (16.3 vs 8.1% in [1-2] year-interval). Oxaliplatine significantly improved annual hazard of recurrence in each year-interval from year 1-4, in colon cancer and in stage III but without impact in rectal cancer and stage II. Conclusion. Extended follow-up to 4 years should be considered in Tunisian population. Impact of oxaliplatine showed same features to reported occidental series (AU)

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Annual hazard rate of relapse of stage II and III colorectal cancer after primary therapy.

PURPOSE: To report the annual hazard of relapse in stages II and III colorectal cancer (CRC) Tunisian patients treated with curative intent. We also aim to evaluate impact of oxaliplatine according to anatomo-clinical features. METHODS: We collected data about clinico-pathological parameters of 331 CRCs. We analyzed annual hazard of recurrence (locoregional and/or distant) of the overall population and several subgroups: colon cancer vs rectal cancer and stage II vs stage III. We also analyzed impact of adjuvant oxaliplatine on recurrence within these subgroups. RESULTS: Relapse rate was 38.1%, with a mean time to relapse of 27.6 months. We noted 23.8% local recurrence, 69.8% distant recurrence, and 6.4% both. We observed higher local relapse rate in rectal cancer (26.8 vs 3.2%) vs colon cancer (p = 0.004). Stage III had a higher metastatic relapse rate vs stage II (31.6 vs 20.8%, p = 0.043). Annual hazard of recurrence for the overall population showed two peaks: [1-2] year-interval by 10.1% and [3-4] year-interval by 11.3%. Stage III showed significantly higher and earlier recurrence hazard peak compared to stage II (16.3 vs 8.1% in [1-2] year-interval). Oxaliplatine significantly improved annual hazard of recurrence in each year-interval from year 1-4, in colon cancer and in stage III but without impact in rectal cancer and stage II. CONCLUSION: Extended follow-up to 4 years should be considered in Tunisian population. Impact of oxaliplatine showed same features to reported occidental series.

Relapse profile of early breast cancer according to immunohistochemical subtypes: guidance for patient's follow up?

PURPOSE: To analyze the profile of annual recurrence rate (ARR) of patients with early breast cancer (BC) in Tunisia. PATIENTS AND METHODS: We classified 293 patients with histologically confirmed early BC relapsing after 1 year of follow up into three subgroups: hormone receptor (HR)+ 'HR' [estrogen receptor (ER)+ or progesterone receptor (PR)+ and human epidermal growth factor receptor 2 (HER2)-], triple negative 'TN' (ER-, PR- and HER2 score 0/1 or fluorescence in situ hybridization (FISH)/chromogenic in situ hybridization negative) and HER2 overexpression 'HER2' (HER2+). ARR was restricted to follow-up contribution of each specified time interval. The HR group was the reference group for comparison. RESULTS: A higher proportion of patients who were up to 35 years old (18% versus 10%, p = 0.04), and patients with obesity (46% versus 26%, p = 0.045) was seen in the TN group. Median time to relapse (MTR) was shorter in TN and HER2 groups than in HR patients (20 and 29 months compared with 56 months, respectively, p < 0.001). In the HR group, the ARR was 22%, 16% and 10% at 3, 4 and 5 years respectively, becoming less than 3% at 7 years. In the TN group, 71% of patients relapsed during the first 2 years and the ARR declined rapidly to less than 1.5% after 4 years. In the HER2 group, the ARR peaked at 2 years (29%) and decreased significantly to 7% and 3% at 5 and 7 years respectively. Adjuvant trastuzumab delayed the MTR from 24 to 34 months (p = 0.022). CONCLUSION: The relapse risk in Tunisian patients is higher in young women and patients with HER2+ and TN tumors. A long and close follow up is recommended for patients with HR and HER2. Conversely, we suggest that follow up in patients with TN could be spaced after 4 years (ARR being <1.5% after this period).

Inflammatory breast cancer in Tunisia from 2005 to 2010: epidemiologic and anatomoclinical transitions from published data.

AIM: To report epidemiologic and anatomoclinical transitions of inflammatory breast cancer (IBC) in Tunisia. MATERIALS AND METHODS: Data including clinico-pathological data for208 cases of T4d or PEV 3 non-metastatic breast cancer diagnosed between 2005 and 2010 were collected from patient records. Chi2 and Z tests were used to compare variables with two Tunisian historical series and a series about Arab-American patients. RESULTS: Thirty three percent of our patients had their first child before 23 years of age and 56% had their menarche before 12 years, 75% never receiving oral contraception. Obesity was observed in 42% of women and IBC occurred during pregnancy in 13% of cases. Tumor grade was II-III in 90% of cases, HR was negative in 52%, HER2 was over expressed in 31% and invasion of more than 3 axillary nodes occurred in 18% of patients. We observed a pCR rate of 19% after neoadjuvant treatment (anthracyline-taxane used in 79%, trastuzumab in 27% ). Compared to historical Tunisian series (since 1996), IBC epidemiology remained stable in terms of median age, menopausal status and obesity. However we observed a significant decrease in median clinical tumor size and number of positive axillary lymph nodes. Comparison to IBC in Arab-Americans showed a significant difference in terms of median age, menopausal status, positivity of hormonal receptors and educational level. CONCLUSIONS: Our assessment of epidemiologic transition showed a reduction of clinco-pathological stage of IBC, keeping the same characteristics as compared to Tunisian historical series over a period of 14 years. Features seem to be different in Arab-American patients, probably related to migration, "occidentalization" of life style and improvement in socio-economic level.

[Uterine sarcoma in Tunisia: retrospective study about 14 cases]. / Les sarcomes utérins en Tunisie : étude rétrospective à propos de 14 cas.

OBJECTIVE: To report epidemiologic, anatomoclinical treatment and results about a Tunisian retrospective serie of 14 patients with uterine sarcoma (US). PATIENTS AND METHODS: A retrospective study of 14 cases of uterine sarcoma treated in the Radiotherapy Unit of Farhat Hached Hospital of Sousse between 1995 and 2008. Epidemiologic and anatomoclinical features were assessed. A complete work-up including abdominal ultrasonography and abdominopelvic CT scan were perfomed in 7 and 10 cases, respectively. RESULTS: The median age was 48.5 years (15 to 78) without previous medical history of irradiation or prolonged drug exposition. There were 3 cases of leimyosarcoma, 7 cases of mixed Mullerian tumor and 4 cases of endometrial stromal sarcoma. The diagnosis was made postoperatively in 6 patients and after curettage in 8 cases. According to the classification of the International Federation of Gynecology and Obstetrics (FIGO), 8 patients were in FIGO stage I, 3 in stage II and 3 in stage III. Hysterectomy was associated with annexectomy in 12 cases. Bilateral pelvic lymphadenectomy was performed in one patient. Eight of our 14 patients underwent postoperative pelvic radiotherapy, associated with adjuvant chemotherapy in 3 cases. The evolution was marked by the occurrence of local recurrence in 4 patients who did not have adjuvant therapy with lung metastases in one case and peritoneal carcinomatosis in another case. With a medium follow-up from 54 months, 7 patients are free from disease, 5 died of their disease (after a mean of 24 months) and 2 patients were lost to follow-up. DISCUSSION AND CONCLUSION: Uterine sarcomas are rare tumors with poor prognosis. Adjuvant therapy (radiotherapy and/or chemotherapy should be discussed due to the high risk of recurrence or metastases.

[Targeted therapies: towards a new toxicology?]. / Thérapies anticancéreuses ciblées: vers une nouvelle toxicologie?

Targeted therapies (TT) represent since 10 years, an interesting progress in oncology for many cancers in adjuvant, neoadjuvant or palliative situation. The development of this new class of drugs, with an original mechanism of action, their easy administration, mainly per os, and a particular toxicity profile different from "classical" chemotherapy (CT) leads them entering in the therapeutic arsenal of breast, digestive tract, lung and hematologic cancers, in association with CT. Medical oncologists took rapidly the train of TT, managing a new and original skin, digestive, cardiovascular, endocrine and pulmonary toxicity profile, that remains relatively less important than "classical" CT.

Treatment for metastatic nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a specific entity different from head and neck carcinoma. Incidence is higher in South-East Asia and North Africa. Prognosis, especially for locally advanced stages (IIB - IVB) and metastasis, remains poor: more than third of cases will present local and/or metastatic recurrence. Overall 5-year survival for all NPC stages ranges from 50% to 70%. The role of chemotherapy in metastasis is well established, and remains an important palliative treatment, although no randomized trial has been reported comparing the different chemotherapy regimens. As 1(st)-line treatment, platin-based regimens seems optimal; in 2(nd) line and after progression under platins, there is no consensus: monotherapy with drugs such as gemcitabine, capecitabine or taxanes has been the most widely tested, with acceptable results. Future trials should integrate targeted therapy, in the light of overexpression of EGFR1 and C-kit in NPC. The present study presents a review of the literature concerning the various studies of metastatic NPC.

[Radiotherapy and combined therapy in breast cancer: standards and innovations in the adjuvant setting]. / Radiothérapie et associations thérapeutiques dans le cancer du sein: actualités et innovations en situation adjuvante.

Due to the significant advances in the diagnosis and treatment of breast cancer seen in the last decades, increased survival rates and better outcomes of patients are being observed. The role of radiotherapy remains pivotal in the treatment of early breast cancer. In the adjuvant setting, whole breast irradiation remains the standard of care using a relatively well standardized radiation technique. The recent technology advances and 3D conformal radiotherapy allow for better volumes definition resulting to increased organ at risk--sparing and therefore treatment optimization. Sophisticated techniques and emerging options (such as accelerated partial breast irradiation) are not routinely used yet outside of a clinical trial. Moreover, new drugs and targeted therapies have recently been introduced to the clinical practice for treatment individualization according to the specific tumours' prognosis and/or prediction of the drugs' efficacy based on new biological tools. Regarding the synergistic effect of these molecules with ionizing radiation, rigorous prospective evaluation of combined therapy is important to ensure improved long-term benefit/risk ratio. In this review, the significant advances of radiotherapy and combined therapy in the new era of breast cancer management will be discussed.

[Sentinel node in breast cancer. Experience of the Salah-Azaïz Institute of Tunis]. / Le ganglion sentinelle dans le cancer du sein. Expérience de l'institut Salah-Azaïz de Tunis.

INTRODUCTION: Breast cancer screening increased the ratio of small tumours. These tumours have a low lymph node metastatic potential. Sentinel node detection allows detecting axillary lymph node invasion without the morbidity of complete axillary lymph node dissection. OBJECTIVES: In this study we report the results of the learning curve of sentinel node detection in the Institut Salah-Azaïz of Tunis. MATERIALS AND METHODS: It is a prospective study between January 2004 and December 2005 in which 115 patients were included with breast cancer less than 3 cm without antecedents of breast surgery. All these women had sentinel node dissection by a colorimetric method and 30% had a combined method (colorimetric and isotopic). RESULTS: The rate of detection was 97.3% (n = 112). An extemporaneous examination was performed in 91 patients. The rate of negative forgery of the extemporaneous examination was 4.3% and the sensitivity of 95.7%. There are no false positive with the extemporaneous exam. The sentinel lymph node was the only node invaded in 15 patients (44%). In 3 patients, the sentinel node was healthy whereas the axillary dissection was positive, so the false negative rate is about 2.6%. CONCLUSION: Sentinel node dissection is a reliable and feasible technique. It however requires a training of the surgeon, the pathologist and the nuclear doctor. It allows to reduce the morbidity of the treatment of the breast cancer by avoiding "useless" axillary dissection out in patients without node invasion. The increase in the number of the small cancers discovered during screening makes it possible to increase the number of patients who can profit from this technique.

[Primary breast lymphoma: a case report]. / Lymphome primitif du sein: à propos d'un cas infraclinique.

BACKGROUND: Non-hodgkinian's lymphoma (NHL) represents 0.04 to 0.53% of all breast cancers. The clinical aspects and therapeutic models of the disease are a subject of debate. AIM: The purpose of this paper is to report the clinical, imaging (sonographic, mammographic and MRI) and pathological features of breast lymphoma, a rare but aggressive tumor, based on a case report review. CASE REPORT: We report a case of primary non-hodgkinian's lymphoma of the breast in one patient aged of 52 years. The patient went to a systematic screening of breast cancer. Physical examen was normal. Mammography showed breast with transitional density, BIRADS type 2, micro-calcifications behind the.... but sometimes it had linear...., neither not distorsion were identified. Ultrasonography did not show a tumor. The disease was revealed by breast MRI. The additional value of MRI in diagnosis is validated in our patient. In fact, when cancer is occult, size evaluation is difficult at standard imaging (7 mm). The diagnosis of non-hodgkinian's lymphoma was confirmed on histological examination of tumor biopsies. It was a B-cell non-Hodgkins-type lymphoma. The clinical features have been reviewed and the tumor have been evaluated both on a morphologic and an immunohistochemical basis. With chemotherapy, the course was favourable. CONCLUSION: The breast is an uncommon site of development of malignant lymphomas. Secondary disease is more common than the primitive form. Primary breast lymphoma is a difficult diagnosis because it is very rare. The diagnosis is mainly histological. Chemotherapy is the principal therapeutic mean. Treatment combines radiotherapy and chemotherapy. Prognosis is generally bad.

High frequency of the V548A fs X572 XPC mutation in Tunisia: implication for molecular diagnosis.

Xeroderma pigmentosum (XP, OMIM 278700-278780) is a group of autosomal recessive diseases characterized by hypersensitivity to UV rays. There are seven complementation groups of XP (XPA to XPG) and XPV. Among them, the XP group C (XP-C) is the most prevalent type in Western Europe and in the United States. We report here on the clinical and genetic investigation of XP-C patients in 14 Tunisian families. As the XPC V548A fs X572 mutation has been identified in Algerian and Moroccan populations, Tunisian patients were first screened for this mutation by a direct sequencing of exon 9 of the XPC gene. All patients with a severe clinical form had this mutation, thus showing the homogeneity of the mutational spectrum of XPC in Tunisia. A potential founder effect was searched and confirmed by haplotype analysis. Taking into account the similarity of the genetic background, we propose a direct screening of this mutation as a rapid and cost-effective tool for the diagnosis of XP-C in North Africa.

[Primary adenoid cystic carcinoma in breast]. / Carcinome adénoïde kystique primitif du sein.

Adenoid cystic carcinoma (ACC) of the breast is a rare neoplasm. We report two observations occurring in female patients, 54 and 65 years old, who consulted for a mastodynia. Clinical examination showed limited painful breast nodules. On ultrasound and mammography they are well-limited bulky mass without microcalcifications. Diagnosis was based on final histopathological exam completed by immunohistochemistry or after slides review. The two patients were treated by mammectomy plus adjuvant radiotherapy and remain alive in remission with a follow-up of 29 and 36 months.

[Breast cancer in Tunisia: epidemiologic characteristics and trends in incidence]. / Cancer du sein en Tunisie: caracteristiques epidemiologiques et tendance evolutive de l'incidence.

The goal of this study is to analyze certain epidemiologic characteristics of breast cancer in Tunisia and to foresee the consequences that will arise from the trends in incidence of this cancer. Data obtained from the North-Tunisia Cancer Registry (NTCR) and from the Salah AZAIZ Institute (SAI) Registry is used to estimate the different incidence rates and to compare these rates with those of other countries. In 15 years the crude incidence rate for breast cancer in the North Tunisia almost doubled to reach 21.5 cases/100,000 women per year during 1994-1998. The high rate of this cancer among women younger than 35 years (11%) could be related to a relatively low incidence among post-menopausal women. The clinical profile of breast cancer remains quite alarming: 40.2% of cases have a tumor with a clinical diameter equal or greater than 5 cm. Birth cohort effect, also know as the generation effect, is expected to lead to an increase of cancer incidence in the future. The rather high number of young cases is a source of additional cost on social and financial level. The priority is now to solve the problem of late diagnosis it has aggravated the prognosis of this cancer in Tunisia.