Nasopharyngeal cancer in non-endemic areas: Impact of treatment intensity within a large retrospective multicentre cohort.

AIM: Recommendations for managing patients with nasopharyngeal carcinoma (NPC) in non-endemic areas are largely derived from studies conducted in endemic areas. We analysed the impact of treatment approaches on survival in non-endemic areas. METHODS: In an international, multicentre, retrospective study, we analyse consecutive patients with NPC diagnosed between 2004 and 2017 in 36 hospitals from 11 countries. Treatment was categorised as non-intensive (NIT), including radiotherapy alone or concomitant chemoradiotherapy (cCRT), and intensive (IT) including cCRT preceded by and/or followed by chemotherapy (CT). The impact of IT on overall survival (OS) and disease-free survival (DFS) was adjusted for all the available potential confounders. RESULTS: Overall, 1021 and 1113 patients were eligible for overall survival (OS) and disease-free survival (DFS) analyses, respectively; 501 and 554 with Epstein Barr-encoded RNA (EBER) status available. In the whole group, 5-year OS was 84% and DFS 65%. The use of NIT was associated with a risk of death or recurrence 1.37 times higher than patients receiving IT. Patients submitted to NIT and induction CT + concurrent concomitant chemo and three-dimensional Conformal Radiation Therapy (3DCRT) had a risk of death or recurrence 1.5 and 1.7 times higher than patients treated with induction CT + cCRT with intensity-modulated radiotherapy (IMRT), respectively. The IT had no impact on OS in neither patients with EBER+ nor in patients with EBER-; IT showed better DFS in EBER+ but not in patients with EBER-. CONCLUSIONS: In low-incidence areas, patients with NPC treated with induction CT followed by concurrent IMRT cCRT achieved the highest DFS rate. The benefit of IT on DFS was restricted to patients with EBER+, suggesting that additional therapy offers no advantages in EBER- cases.

Primary Squamous Cell Carcinoma of the Trachea: Two Cases Report.

Tracheal squamous cell carcinoma is the most common pathology in smokers while ACC is more prevalent among non-smokers. These tumors tend also to be diagnosed late on account of delayed specific symptoms as hemoptysis, dyspnea, cough, hoarseness, and stridor being the most common. Management of tracheal tumors is essentially multidisciplinary. It includes interventional endoscopy, surgery, radiotherapy, and/or end luminal brachytherapy. Extensive segmental resection of the trachea is the potentially curative treatment of choice for primary lesion. The sleeve trachea resection is one of the optimal surgical modalities. The other options are: partial tracheal wall resection and immediate tracheal reconstruction, total laryngectomy plus partial resection of trachea and primary reconstruction, laryngeo-tracheal resection, cervico-mediastinal exenteration, or carinal resection and reconstruction. Trachea anastomosis is suitable for small defects. The platysma myocutaneous flap combined with the facial flap of the sternohyoid muscle, sternocleidomastoid myoperiosteal flap and the pectoralis major musculocutaneous flap are applied to reconstruct the defects of cervical trachea. Post-operative radiation therapy, in many cases, is considered a fundamental part of treatment. Contraindications to surgery include: metastatic disease, invasion of adjacent organs, involvement of airway greater than could be safely resected (i.e. >50% of trachea), involvement of airway that would leave grossly positive margins after resection, spinal kyphosis, or poor medical condition of the patient. Patients in the current report tolerated therapy well with the use of modern RT techniques and dose delivery to 60 to 64 Gy to a large extent of the central airway. Additional data and meta-analysis are required to validate the efficacy of chemoradiation in comparison to primary RT alone for unresectable cases and subsequently identify improved systemic therapies. Further investigation into the potential role of additional therapies, such as adjuvant chemotherapy or immunotherapy, may be worth exploring. Our initial findings suggest the use of concurrent chemotherapy in addition to RT in patients with locally advanced tracheal SCC.

Phase II/III Randomized Controlled Trial of Concomitant Hyperfractionated Radiotherapy plus Cetuximab (Anti-EGFR Antibody) or Chemotherapy in Locally Advanced Head and Neck Cancer.

INTRODUCTION: Globally, there is marked variation in overall incidence and presentation of head and neck cancers, these cancers account for 11.5 per 100,000 population in G.C.C states. Concomitant chemotherapy and external beam radiotherapy (EBRT) is indicated in such cancers with aim of organ preservation, control and possible cure. Hyper fractionated radiotherapy with concomitant chemotherapy or cetuximab is a lesser explored option. In this study we wish to assess the tolerability and efficacy of cetuximab with altered fractionation and compare this with the chemotherapy (cisplatin). MATERIALS AND METHODS: This is a randomized controlled study from a single institute in Kuwait. Locally advanced head and neck cancer cases excluding cancer nasopharynx are enrolled for the study. Stage III or stage IV-A cases were enrolled with histopathology squamous cell carcinoma. Patients were randomized into 2 arms. Arm A: to receive platinum-based CT i.e. cisplatin in a dose of 100 mg/m2 3-weekly or 40 mg/m2 weekly during radiation; Arm B: received cetuximab with a loading dose 400 mg/m², one week before radiation followed by weekly dose of 250 mg/m² during radiation. Radiotherapy was delivered using intensity modulated radiotherapy (IMRT) or 3D-conformal radiotherapy (CRT). The primary objective was to evaluate whether the use of cetuximab with concurrent hyperfractionated radiation regimen will have loco regional control rates (LC) and Disease-free survival (DFS) that are comparable to concurrent cisplatin in patients with LAHNC. The secondary endpoints were to compare the impact of using concurrent cetuximab vs chemotherapy regimen on Overall Survival of patients (OS) and acute and late adverse events. RESULTS: From November 2012 to November 2017, 40 patients were randomized. The median age of was 51 years (range 27-72 years). Thirty-five patients are male and remaining was female. 14 patients have their primaries in larynx, 11 in oropharynx, 8 in oral cavity, and 5 has tumor in hypopharynx. Two patients had disease in nasal sinus or overlapping subsides. 50% has T4 lesions while 35% has T3 lesions, Nodal status was (N0-1) in 20 patients and (N2-3) in 20 patients. Overall staging showed a majority to have stage IV disease (63%). HPV was negative in 2 cases in Arm 1 and positive in 2 cases in Arm 2. 22 patients were randomly allocated in Arm A (platinum-based) while 18 were in Arm B (cetuximab). CR was achieved in 59% in arm A vs 50% in Arm B, while PR was 27.3% and 27.8% respectively. Disease progressed in 2 patients in Arm B only. Out of these 40 patients, 14 patients failed (6 and 8 in arm A and B respectively). Locoregional failure was documented in 6 (27.3%) vs 7 (38.9%) of arm A and B respectively, which was statistically not significant possibly related with lower number of cases. 2 years DFS was 56.5% vs 77.3% in cisplatin vs cetuximab arm (denoting nonsignificant increase of relapse rate in cisplatin arm). However, 2 years OS was 80.7% vs 57.3% in cisplatin and cetuximab arm respectively (p value=0.04). CONCLUSION: Though cetuximab has lesser side effects but it is not indicated in treatment of LAHNC. Concurrent cisplatin is a trusted option for concomitant setting regardless of the HPV status and tumor location. However, in the context of cisplatin ineligible patients, cetuximab should be used only with hyper fractionation. This preliminary study could represent a good core of large international multicenter RCT.

Triple Negative Breast Cancer: 10-Year Survival Update of The Applied Treatment Strategy in Kuwait.

BACKGROUND: Triple negative breast cancer (TNBC) is recognized as a distinct clinical and biological entity of poor outcome for almost two decades, yet its treatment strategy still needs to be better specified. The study aim is to update the 10-year survival data of our TNBC patients and to find its association with different treatment modalities. PATIENTS AND METHODS: We updated the 10-year survival data of 359 women diagnosed with TNBC between 1999 and 2009 in the Kuwait Cancer Control Center (KCCC). The overall survival (OS), disease free survival (DFS), distant metastasis free survival (DMFS) and loco-regional recurrence free survival (LRFS) were estimated using Kaplan Meier method. Survival was correlated with different prognostic factors and treatment modalities. Statistical significance was calculated using the log-rank test and defined as p < 0.05. Cox regression is used for Multivariate analysis. RESULTS: TNBC represented 12% of breast cancer in Kuwait with a median age of 48 years. The stage distribution was as follow: stage I, II, III, IV in 15%, 43%, 35% and 7% of patients respectively. Regarding surgery, 33% had Conservative surgery; 67% had mastectomy; 82% had axillary clearance. Chemotherapy was neoadjuvant in 25%, adjuvant in 56% and palliative in 5% of patients. Two-thirds of patients (67%) received adjuvant radiotherapy. After a median follow-up of 108 months, the 10-year OS, DFS, DMFS and LRFS were 66%, 59%, 72% and 77% respectively. The 10-year OS was 92%, 80%, 49% and 0% for Stage I, II, III and IV respectively (p =< 0.0001). OS was significantly worse with the presence of lymphovascular invasion (LVI) with p = 0.003. OS was not significantly affected by age, grade or treatment modality. In multivariate analysis, the clinical stage and LVI were still significant (P<0.0001 and 0.04 respectively). CONCLUSION: In the absence of biological biomarkers, clinical stage and LVI seem to be the only significant prognostic factors for survival of TNBC patients in our study population. Timing of chemotherapy as well as the extent of surgery do not seem to affect the TNBC patients' outcome.

Metastatic renal cell carcinoma with undetectable renal mass presenting as lymphadenopathy.

Renal cell carcinoma has the ability to metastasize to any organ; about 16 % of affected patients present initially with metastasis. However, it is rare for this tumor to present with metastasis from an unidentified primary. The current use of immunohistochemistry and molecular genetics has enabled clinicians to reach a precise diagnosis. It has been hypothesized that the treatment protocol for metastatic renal cell carcinoma can be applied to cases with undetectable primary. In this paper, a novel case of metastatic renal cell carcinoma presenting with lymphadenopathy with no evidence of a primary renal lesion is reported from Kuwait cancer center.

Phyllodes tumors of the breast: Analysis of 35 cases from a single institution.

BACKGROUND: Phyllodes tumors are rare fibroepithelial breast tumors with diverse biological behavior. Our study aim is to review the clinico-pathological features, prognostic factors and treatment outcome for patients presenting with phyllodes tumors of the breast to the Kuwait Cancer Control Center (KCCC). PATIENTS AND METHODS: We retrospectively reviewed the clinical and pathological data of 35 women of histologically proved phyllodes tumors of the breast retrieved between January 1994 and December 2012. RESULTS: The median age was 40years (21-63years). The median pathological tumor size was 6.8cm (3-25cm). Histologically, one patient (3%) presented with benign, 13 (37%) with borderline and 21 (60%) with malignant phyllodes. Twenty-eight patients (80%) were premenopausal. Twenty (57%) were ultimately treated with mastectomy (3 borderline, and 17 malignant) and 15 (43%) with conservative surgery (1 benign, 10 borderline and 4 malignant). Axillary staging was carried out in 9 patients (1 borderline and 8 malignant), none of them had nodal metastasis. Four patients with malignant phyllodes received postoperative radiotherapy. After a median follow-up period of 52months (range 5-211months), 5 developed local recurrence (1 benign, 2 borderline and 2 malignant). One patient with malignant phyllodes developed distant lung metastasis. The overall 5-year relapse free survival (RFS) was 74% (68% for borderline and 84% for malignant phyllodes). According to the treatment modality, the 5-year RFS was 69% for conservative surgery compared to 87% for mastectomy. It was 100% for irradiated patients versus 71% for non irradiated patients. CONCLUSION: Phyllodes tumors are rare tumors that occur in relatively young women, when compared with the classical adenocarcinoma of the breast. They have a tendency to reach large sizes with absence of nodal metastasis. Although surgery is the mainstay of management, postoperative radiotherapy also appears to decrease the local recurrence rates in certain presentations.

Significance of Magnetic Resonance Imaging-Assessed Tumor Response for Locally Advanced Rectal Cancer Treated With Preoperative Long-Course Chemoradiation.

PURPOSE: To study the predictive and prognostic value of magnetic resonance imaging (MRI)-assessed tumor response after long-course neoadjuvant therapy for locally advanced rectal cancer. METHODS: This study included 79 patients who had T3 or T4 and/or N+ rectal cancer treated with long-course neoadjuvant chemoradiation. MRI-assessed tumor regression grade (mrTRG) was assessed in 64 patients. MRIs were reviewed by the study radiologist. Surgical and pathologic reports for those who underwent surgery were reviewed. Disease-free survival (DFS) was estimated. Progression during therapy, local relapse, metastasis, and death resulting from the tumor were classified as events. Statistical significance was calculated. RESULTS: In 11 patients, the tumor completely disappeared on MRI; that is, it had an mrTRG of 1. All but one patient, who chose deferred surgery, had a complete pathologic response (pCR), with a positive predictive value of nearly 100%. Of the 20 patients who had an mrTRG of 2 on MRI, six had a pCR. mrTRG 3, mrTRG 4, and mrTRG 5 were detected in 24, six, and three patients, respectively, of whom only one patient had a pCR. The 2-year DFS was 77%. The mrTRG was significant for DFS. The 2-year DFS was 88% for patients with a good response versus 66% for those with a poor response (P = .046). CONCLUSION: MRI-assessed complete tumor response was strongly correlated with pCR and, therefore, can be used as a surrogate marker to predict absence of viable tumor cells. Our results can be used to implement use of mrTRGs in larger prospective correlative studies as a tool to select patients for whom deferred surgery may be appropriate. Also, those with a poor response may be offered further treatment options before definitive surgery.

Clinicopathological features and prognosis of triple negative breast cancer in Kuwait: A comparative/perspective analysis.

AIM: The aim of this study was to determine the incidence of TNBC in Kuwait, to analyze the clinicopathologic features and prognosis of this type of breast cancer, and compare it with reports from other regions of the world. BACKGROUND: Triple negative breast cancer (TNBC) is defined as a subtype that is negative for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2). There is a growing evidence of the heterogeneity of such entity on the molecular level that may cause discrete outcomes. METHODS: We analyzed the clinicopathologic features of 363 TNBC cases which were diagnosed in Kuwait from July 1999 to June 2009. The disease-free survival (DFS) and overall survival (OS) were analyzed by Kaplan-Meier method. Comparison was done with reports from USA, Europe, Middle and Far East. RESULTS: Among 2986 patients diagnosed with breast cancer in Kuwait, 363 patients (12.2%) were TNBC. The median age was 48 years, 57.2% had lymph nodes (LN) metastasis, 56.9% were of grade III tumor and 41.9% had stage II disease. 81% developed recurrences and 75% of deaths occurred by 2.5 years after treatment. There is marked variation of clinicopathologic features according to country of patients' cohort. CONCLUSION: The incidence of TNBC in our study is similar to other studies. TNBC patients showed an early major recurrence surge peaking at approximately year 2.5. Regional variation of clinicopathologic features indicates a need for molecular studies to define underlying molecular features and its impact on survival.