Recurrent thyroglossal duct cysts: a 23-year experience and a new method for management

OBJECTIVES: We present an experience in the management of primary and recurrent thyroglossal duct cysts (TGDCs) and describe a novel method for recurrent TGDC removal. METHODS: We performed a retrospective review of TGDC surgery at Children's Hospital in Seattle from 1980 to 2003. The surgical techniques for primary and recurrent TGDCs and the factors associated with TGDC recurrence were evaluated and analyzed. RESULTS: During the study period, 231 patients underwent 296 TGDC surgeries. Thirty-four of the 231 patients (15%) underwent a total of 88 procedures for recurrent TGDCs. Successful procedures used for secondary TGDC management included central neck dissection with directed base of tongue (BOT) excision in 6 of 9 patients (67%), secondary Sistrunk operation with limited BOT resection in 12 of 27 patients (44%), revision Sistrunk operation with BOT dissection in 7 of 11 patients (64%), and suture-guided transhyoid pharyngotomy in 8 of 8 patients (100%). Ten of the 231 patients (4%) had initial TGDC incision and drainage and then underwent a total of 21 procedures, excluding the incision and drainage. The factors associated with TGDC recurrence were inaccurate initial diagnosis (17 of 34 or 50%), infection (5 of 34 or 15%), unusual TGDC presentation (5 of 34 or 15%), and lack of BOT musculature removal (7 of 34 or 20%). The level of surgeon training affected the surgical outcome. CONCLUSIONS: Successful TGDC treatment requires consideration of factors associated with recurrence. Recurrent TGDCs can be treated by several methods, including suture-guided transhyoid pharyngotomy.     

Outcome of thyroglossal duct cyst excision is independent of presenting age or symptomatology

BACKGROUND: Thyroglossal duct cysts (TGDCs) are the most common form of congenital neck cyst, accounting for up to 70% of such lesions. There has been no consensus on which factors predict outcome of thyroglossal duct cyst excision. The objective of the current study is to evaluate the relevance of symptomatology and age at presentation with outcome of TGDCs. METHODS: Retrospective review of patients with TGDC at a tertiary care children's hospital. Data collected included patient's age, gender, clinical presentation, presence or absence of preoperative infection, imaging modality, type of procedure performed, size and location of the lesion, postoperative infection, complications, and recurrence of disease. RESULTS: Twenty-nine patients were identified (59% female, 41% male). Age of presentation was bimodal and ranged from 18 months to 14 years. The most common presenting symptom was the presence of an asymptomatic midline neck mass (76%). A history of preoperative TGDC infection was present in 22% of patients /=5 years of age. Recurrence rate after the Sistrunk procedure was 3.4%. CONCLUSIONS: The finding of a midline neck mass is the most common presentation of TGDCs in toddlers, whereas infection is the most common presenting symptoms in school-aged children. The incidence of preoperative infection was 41% in our series, much higher than previously reported. Independent of presenting age and symptomatology, recurrence of TGDC remains low when the Sistrunk procedure is employed.     

超声对特殊部位甲状舌管囊肿的诊断价值

目的探讨超声对于特殊部位甲状舌管囊肿的诊断价值。方法回顾性分析超声图像资料,总结特殊部位甲状舌管囊肿的超声表现并判断超声对病变诊断的准确性。结果 5例位于舌根部,1例位于声门下,超声显示率100%,超声定位准确率100%。超声表现:肿块大小1.1 cm×1.1 cm×1.2 cm～2.4 cm×2.2 cm×1.9 cm;均为类圆形;6例(100%)均为薄壁;4例(67%)内呈无回声,2例(33%)呈均匀低回声;5例(83%)为单房、无分隔,1例(17%)为多房、有细小分隔;后方回声均增强;所有肿块内部及周边均未见血流信号。结论舌根部和喉内甲状舌管囊肿易导致儿童气道梗阻,超声对舌根部和喉内甲状舌管囊肿定位准确,有助于明确病变范围。     

Endoscopic management of intralingual thyroglossal duct cysts: Case series and systematic review

ObjectiveTo discuss our institutional experience with endoscopic management of intralingual thyroglossal duct cyst (TGDC) and review cases in the published literature in a systematic review.MethodsPediatric patients with intralingual TGDC treated with endoscopic surgery at our institution from 2009-2019 were identified. Metrics from our case series were then compared to those in the literature in a systematic review to assess pooled outcomes of endoscopic or transoral management. Patient demographics, age of presentation, presenting symptomatology, size of cyst on imaging, type of surgery, and post-operative outcomes were assessed.ResultsWe identified 5 institutional cases of intralingual TGDC and 48 cases of intralingual TGDC described in the literature. The average age of presentation was 20.36 months. 69.8% (N=37) of patients presented with at least one respiratory symptom, 22.6% (N=12) presented with dysphagia, 9.4% (N=5) presented with an identified mass in the oropharynx, and 15.1% (N=8) had the cyst discovered as an incidental finding. Three patients required revision surgeries due to prior incomplete TGDC excisions and one patient experienced a recurrence >6 months after primary excision requiring a second procedure. Our data pooled with published case series in systematic review confirms that endoscopic or transoral management are excellent options for definitive management of intralingual TGDC.ConclusionsIntralingual TDGC is a potentially life-threatening variant of TGDC. Our results pooled with published series in a systematic review suggest that endoscopic or transoral management of intralingual TGDC are excellent minimally invasive treatments with a low risk of recurrence. Postoperative surveillance up to one year is recommended.     

A prospective study of PET-FDG imaging for the assessment of head and neck squamous cell carcinoma

The main aim of the study was to evaluate the use of positron emission tomography using fluoro-deoxyglucose (PET-FDG) imaging for the detection of squamous cell carcinoma of the head and neck. Fifty-four consecutive patients with malignancies involving the head and neck were studied prospectively. Thirty-one patients presented with primary disease and 23 were suspected of recurrent or residual disease. All patients underwent full clinical staging, PET-FDG scans and anatomical imaging, 37 underwent computed tomography (CT), 13 magnetic resonance (MR) and four had both CT and MR. Clinical assessment, CT/MR, PET-FDG and histological examination were all evaluated independently of each other. All 31 primary head and neck malignant tumours were detected by PET-FDG. Based on 16 patients who underwent neck dissections, the sensitivity and specificity of PET-FDG for detecting nodal disease was 67% and 100% respectively, compared with clinical assessment of 58% and 75% and CT/MR of 67% and 25%. In all 12 patients, PET-FDG correctly identified the presence or absence of recurrent or residual disease. PET-FDG staged 13 post-treatment necks with an accuracy of 100%, as compared to CT/MR which was accurate in 7 of 13 and clinical assessment which was accurate in eight. Three sites of abnormal tracer uptake unrelated to malignancy were recorded as incidental findings (mandibular osteomyelitis, 1; post glossectomy site, 2). PET-FDG was more accurate than CT/MR for identifying primary and recurrent tumours as well as metastatic lesions in the neck. If these diagnostic properties of PET-FDG are confirmed in further prospective studies, it could prove a valuable adjunct for the management of head and neck cancer.     

“Extended” Sistrunk procedure in the treatment of recurrent thyroglossal duct cysts: A 10-year experience

Objective

We report a 10-year experience of children with recurrent thyroglossal duct cysts (TGDCs) who have been treated using the “extended” Sistrunk procedure.

Methods

We performed a retrospective review of TGDC surgery from 2004 to 2013. Sistrunk operation was the procedure of choice in all patients. Seven children had TGDC recurrence. All of them underwent “extended” Sistrunk procedure. Follow up ranged from 6 months to 8 years.

Results

There were no gender differences, all recurrences presented within 12 months follow-up in the same location of the primary cyst. Five out of 7 (71%) patients have been treated for preoperative and 2/7 (29%) for postoperative infection at the time of primary surgery. Pathological examination of the surgical specimens showed a single tract in 2 children (29%) and multiple tracts in 5 (71%). We did not observe postoperative complications or further recurrences.

Conclusion

Our experience suggest that recurrent TGDCs are equally common in both sexes, develop in the same location of the primary cyst and recur more commonly after perioperative infections. The “extended” Sistrunk procedure is highly effective and safe in treating recurrent TGDCs also if multiple duct tracts are detected.     

Interpretation of suspect head and neck fixations seen on PET/CT in lung cancer

ObjectivesSmoking is the major risk factor for lung and head and neck cancer. The purpose of the present study was to determine the clinical impact of serendipitously revealed head and neck fixation on PET/CT in patients undergoing investigation for lung cancer.Material and methodsThe reports from PET/CT studies for patients with lung cancer from September 2005 and April 2012 were retrospectively reviewed. Head and neck incidentaloma was interpreted as suggestive of second primary malignancy. These incidental findings were compared with the final diagnosis obtained from clinical and histological investigation.ResultsFive hundred and ninety-two patients were investigated on PET/CT for lung cancer in the study period. PET/CT-positive head and neck lesions suggestive of second primary malignancy were found in 65 (11%) patients. Nasoendoscopy was performed in 23 patients and biopsy in 10. In 4 patients (17.4% of those explored), a second primary malignant lesion was proved on histology: 2 squamous cell carcinomas (larynx and oral cavity), 1 undifferentiated carcinoma (parotid), and 1 osteosarcoma (mandible). At a median 13 months’ follow-up, 3 of the 4 patients with a second primary had died from disease-related causes and 1 was free of recurrence. Metastases from lung adenocarcinoma were found in 2 patients (0.34%).ConclusionsPET/CT detected incidental head and neck malignant tumors in at least 0.68% of lung cancer patients, but in 6.4% of those with suspect head and neck fixation.     

Examination of care processes and treatment optimization for head and neck cancer patients in a community setting “hub and hub” model

ObjectiveTo examine referral pattern, the timing of diagnostic/staging processes, and treatment initiation for new head and neck cancer patients in a community setting.MethodsPatients with a newly diagnosed previously untreated diagnosis of head neck cancer managed at Asplundh Cancer Pavilion/Abington Memorial Hospital from October 2018 to March 2020. Source of referral and preceding workup were examined as well as intervals between initial head and neck consult and various timepoints of treatment initiation.ResultsOne hundred and five patients were included in the study. The primary referral sources were external general otolaryngology (56.3%). Oral surgery and dermatology obtained tissue biopsy approximately 80% of the time before referral. The average time from the ordering of initial staging positron emission tomography/computed tomography to finalized results was 14 days (range: 10–25 days). Patients referred from dermatology and oral surgery were more likely to require single modality care, namely definitive surgical management. Time to treatment initiation average was 37 days (range: 29–41 days). Patients with longer treatment times noted significantly higher times to both radiation and medical oncology consults (48.42 vs. 18.13 days; P < 0.001).ConclusionsNo notable differences in treatment initiation times were identified based on referral source or extent of workup performed before head/neck surgery consult. It appears the largest opportunities for improvement in terms of reducing overall treatment length exist in the optimization of radiation initiation time.     

Thyroglossal duct cysts: presentation and management in children versus adults

OBJECTIVES: To determine if the clinical presentation of thyroglossal duct cysts (TGDC) varies between children and adults and whether this knowledge helps optimize the surgical management. METHODS: We retrospectively identified all patients with TGDC managed in our department between 1992 and 2002. We reviewed the patients' charts and recorded their gender, age at diagnosis, clinical presentation, radiologic imaging, surgical management, post-operative complications, and recurrence rate and compared the variables between the children and adults. RESULTS: Twenty-one children and 41 adults were treated for TGDC. Of the children, 57% were male and 43% were female, whereas 49% of the adults were male and 51% were female (P = 0.53). The average age was 6 +/- 5 years in children and 45 +/- 16 years in adults, which demonstrates a bimodal distribution. Forty-three percent of children and 42% of adults presented with an infected neck mass (P > 0.99). Among our patients, 96% of the adults and 100% of the children underwent a Sistrunk operation. Four children developed a wound infection that resolved with antibiotics. One adult developed a haematoma and another developed a wound seroma. There was one recurrence among adults and one among children, both of whom were treated with a second Sistrunk procedure. CONCLUSIONS: There appears to be a bimodal distribution for age at presentation of TGDC. Since the differential diagnosis among adults is broader, the opportunity for misdiagnosis is greater. However, once the correct diagnosis is made, the surgical management and post-operative outcome between adults and children is the same.     

Endoscope-assisted intra-oral resection of the external thyroglossal duct cyst

Objective

Surgical removal of a thyroglossal duct cyst (TGDC) and its tract is usually accomplished through an external neck incision, including the removal of the middle part of hyoid bone and a block of tissues extending to the foramen cecum. However, this procedure inevitably results in neck scarring. We implemented a modified approach to TGDC removal in a 28-year-old woman through the floor of the mouth using an endoscope system.

Case report

Here, we describe the detailed procedure of the endoscope-assisted intra-oral resection for TGDC. The total operative time was 130 minutes. The patient complained of swelling and pain in the floor of the mouth for 2 days, but did not require any intervention. Follow-up imaging studies confirmed no recurrence (18 months) without any sequelae, and the patient was satisfied with her surgical outcome.

Conclusion

The intra-oral approach through the floor of the mouth is a technically feasible alternative surgical option that allows for complete removal of a TGDC without the neck scar.     

Primary solitary extramedullary plasmacytoma of the tongue

Extramedullary plasmacytomas are rare malignancies. Most cases (80%) are seen in the head and neck region, where they represent 1% of all head and neck malignancies. We report a case of an extramedullary plasmacytoma of the tongue that was treated successfully with three-dimensional conformal radiotherapy. The patient was a 50-year-old woman who was admitted to our hospital with bilateral pain and ulceration on the sides of her tongue. Findings on magnetic resonance imaging and positron-emission tomography did not demonstrate any mass within the tongue or any lymphatic or distant metastasis. A tissue biopsy identified a plasma cell neoplasm. The patient was treated with a total dose of 50 Gy delivered in 2-Gy daily fractions. After 54 months of post-treatment follow-up, she exhibited no sign of systemic myeloma or local recurrence. This case is presented not only for the rarity of the tumor type, but also for its unusual location.     

Incidental findings on MRI scans of patients presenting with audiovestibular symptoms

Background

The evaluation of patients presenting with audiovestibular symptoms usually includes MRI of the internal auditory meatus, the cerebellopontine angle and the brain. A significant percentage of these scans will present unexpected, incidental findings, which could have important clinical significance.

Objective

To determine the frequency and clinical significance of incidental findings on MRI scans of patients with audiovestibular symptoms.

Materials and methods

A retrospective analysis of 200 serial MRI scans.

Results

Gender distribution: equal. Age range: 17-82 years. One-hundred and four scans (52%) were normal and 1 scan (0.5%) demonstrated a unilateral vestibular schwannoma. Ninety-five scans (47.5%) demonstrated incidental findings. Sixty-six of these (33%) were considered of ishaemic origin and did not require further action. Five (2.5%) scans demonstrated significant findings which warranted appropriate referral; Two Gliomas (1%), 2 cases of extensive White Matter Lesions (1%), 1 lipoma (0.5%). The remaining scans demonstrated various other findings.

Conclusion

Investigation of patients with audiovestibular symptoms with MRI scans revealed incidental findings in a significant percentage (47.5%). The majority of these findings were benign warranting no further action and only 2.5% required further referral. It is the responsibility of the referring Otolaryngologist to be aware of these findings, to be able to assess their significance, to inform the patient and if needed to refer for further evaluation.     

Squamous cell carcinoma metastatic to the neck from an unknown head and neck primary site

Squamous cell carcinoma metastatic to the neck from an unknown head and neck primary site is relatively uncommon and presents a challenging diagnostic and therapeutic dilemma. Diagnostic evaluation includes fine-needle aspiration of the neck mass, chest roentgenography, computed tomography, and/or magnetic resonance imaging of the head and neck, followed by panendoscopy and biopsies. The primary tumor will be detected in approximately 40% of patients; approximately 80% of cancers are located in the base of the tongue or tonsillar fossa. Management options include treatment of the neck alone or both sides of the neck and the potential head and neck primary sites. The latter approach is associated with better long-term control above the clavicles. The 5-year survival rate is approximately 50% after treatment and is influenced by the extent of neck disease. In this article, we review the pertinent literature.     

Safety of the “incidental” neck dissection or exploration during free tissue transfer after head and neck irradiation

ImportancePatients with either local recurrence of head and neck cancer or osteoradionecrosis after prior radiation treatment often require free tissue transfer for optimal reconstruction. In this setting, neck exploration for vessels is necessary, and an “incidental” neck dissection is often accomplished despite clinically negative cervical lymph nodes. While neck surgery in the post-radiated setting is technically challenging, the safety of post-radiated elective neck dissection or neck exploration for vessels is not well-studied, especially for patients undergoing non-laryngectomy salvage resections.ObjectiveTo define intraoperative and postoperative surgical complications for patients undergoing elective neck dissection or exploration with free tissue transfer reconstruction in the post-radiated setting, with attention to complications from neck surgery.DesignRetrospective cohort study. Patient charts from May 2005 to April 2020 were reviewed.SettingTertiary care referral center.ParticipantsPatients underwent free tissue transfer after prior head and neck irradiation for non-laryngeal local cancer recurrence or second primary, osteoradionecrosis, or for sole reconstructive purposes. Patients with clinically positive neck disease were excluded.Main outcomes and measuresIntraoperative and postoperative complications including unplanned vessel or nerve injury, hematoma, chyle leak, wound dehiscence, wound infection, fistula formation, flap failure, and perioperative medical complications. Neck exploration and neck dissection patient outcomes were compared by Fisher exact test.ResultsSeventy-two patients (56 men and 16 women) of average age sixty-one (range 34–89) were identified with average follow-up 25.7 months. Most patients (78%) underwent salvage neck dissection, and the rest underwent neck exploration for vessels only. There were five intraoperative neck complications: three vessel injuries and two nerve injuries. There were twenty-six postoperative surgical complications among eighteen patients. There was no difference in surgical complications whether patients underwent neck dissection or exploration only. Two partial and two complete flap failures occurred. There were nine perioperative medical complications among six patients.Conclusions and relevanceElective neck dissection or exploration among patients undergoing free tissue transfer in the post-radiated setting carries a risk of both intraoperative and postoperative surgical complications. The present study defines risk of complications and helps to inform patient discussions for risk of complications in the post-radiated setting.     

Long-Term Clinical Course of Benign Fibro-Osseous Lesions in the Paranasal Sinuses

ObjectivesFibro-osseous lesions of the paranasal sinuses can present various clinical manifestations. This study aimed to report the long-term clinical course of benign fibro-osseous lesions (BFOLs) in the paranasal sinuses, including clinical and radiologic features.MethodsRadiologically confirmed BFOLs between 1994 and 2016, with the exclusion of osteoma cases, were retrospectively reviewed. We compared demographic characteristics between the surgery and observation groups. The reasons for the imaging study, radiographic features, histopathology, and clinical course based on serial image scans were analyzed.ResultsIn total, 183 subjects were selected from a thorough review of head and neck radiologic tests (n=606,068) at a tertiary referral hospital over 22 years. Patients’ mean age was 28.6±18.1 years, and 56.3% were males. A diagnostic imaging workup was performed in 55.7% of patients due to facial asymmetry, headache, skull mass, or other symptoms related to BFOLs. In other patients (37.7%), BFOLs were found incidentally on computed tomography or magnetic resonance imaging. The most common diagnosis was fibrous dysplasia, followed by ossifying fibroma, based on both radiologic exams and histopathologic results. In total, 42.6% of the patients underwent surgery because of subjective symptoms or esthetic concerns. The patients who underwent surgery were younger (P<0.001) and had a longer follow-up duration (P<0.001) than those who underwent observation. Patients who experienced lesion growth (11.5%) were younger (P<0.001) and had more lesion sites (P=0.018) than those who did not, regardless of surgical treatment. Five patients underwent optic nerve decompression, and one patient experienced malignant transformation.ConclusionBFOL in the paranasal sinuses is a rare disease, and most cases were observed without specific treatment. Surgical treatment should be considered in symptomatic patients with aggressive clinical features. Regular observation and management are needed, particularly in younger patients in their teens.     

Comparison between 18F-FDG PET and conventional imaging techniques (CT SCAN and MRI) in the diagnosis of head and neck tumor suspicion of recurrence

BackgroundThis study aimed to assess the results obtained with the positron emission tomography (PET) and conventional anatomic imaging methods (CT scan and MRI) in the diagnosis of suspicion of tumor recurrence in head and neck cancers.MethodsThirty patients with suspicion of tumor recurrence due to head and neck cancers were reviewed retrospectively. Consequently, 34 PET studies were performed. The images were obtained in the PET Institute of Madrid. They were interpreted by visual and semiquantitative analysis. The results were confirmed with clinical followup, response to treatment or with histological studies in some cases.ResultsSensitivity and specificity of the PET were 95.6% and 81.8% respectively, while it was 65% and 80% for the CT scan/MRI.ConclusionsWe can conclude that PET provides better results than conventional imaging techniques in the detection of head and neck cancer recurrence.     

Thyroglossal duct cyst excision with hyoid bone preservation

The objective of this study is to assess complete removal of the thyroglossal duct cyst (TGDC) and its tract(s) to the base of the tongue with sparing of the hyoid bone. This is a prospective cohort study. Tertiary hospital (Zagazig university hospital). This prospective study was carried out on 21 patients who had been diagnosed preoperatively as TGDC or fistula. All patients were managed by dissection and removal of the TGDC and its tract(s) to the base of the tongue with sparing of the hyoid bone. The study was conducted on 12 males (57.14 %) and 9 females (42.85 %) with mean age 6.8 years (4–20 years). After histopathological examination; 16 patients (9 male and 7 female) were proved to have TGDC and 5 patients (3 male and 2 female) were proved to have dermoid cyst. The hyoid bone could be preserved in all cases except in two cases for whom the middle third of the hyoid bone was removed with the specimen. Multiple tracts were found in three cases and could be identified and dissected successfully with sparing of the hyoid bone. Identification, dissection, and complete excision of the TGDC with its attaching tract(s) could be performed without hyoid bone resection with no recurrence and minimal minor complication. The impacts of this hyoid bone preservation versus removal on the pattern of swallowing and retroglossal space need to be studied.     

Doxycycline: A sclerosant agent to treat a case of recurrent thyroglossal duct cyst

Thyroglossal duct cyst (TGDC) is one of the most common congenital anterior midline neck masses in children. Sistrunk operation is considered as the cornerstone in TGDC removal. Nevertheless, 5% to 7 % of patients have been reported to show a recurrence even after adequate resection. This necessitates at times multiple resections with potential complications. One interesting emerging technique is sclerotherapy of TGDC remnants post resection. We present here a case of a child who had a successfully treated recurrent TGDC using sclerotherapy with doxycycline.     

头颈部淋巴管畸形的CT诊断价值

目的 探讨儿童头颈部淋巴管畸形(lymphatic malformation, LM)的CT表现及诊断价值。方法 回顾性分析2016—2021年收治的57例经手术及病理证实的头颈部LM患者的CT资料。结果 2岁以内41例,病灶位于左侧26例,右侧26例,双侧5例;位于颈部、咽旁26例,头面部8例,跨越头面、颈或纵隔23例。临床表现无痛性肿块53例,面容改变25例,喉喘鸣、呼吸困难或吞咽困难7例,上述临床表现可单独或者同时出现。单房型25例,多房型32例;瘤内合并出血者30例;55例CT诊断LM,阳性率96.5%(55/57)。CT可表现单房或多房,呈圆形、不规则形及分叶状低密度或等密度影,沿着组织间隙呈现爬行性生长,边界清楚或不清,部分患者可见分隔影,增强后囊内容物不强化,纤维状分隔及囊壁呈点状、条状、条索状及网格状强化。合并感染或出血时CT值升高,部分患者可见液-液平面。结论 CT检查能清晰显示头颈部LM的位置、大小和累及范围,且具有一定的特征性表现,对LM的诊断和制定治疗方案具有重要价值。     

Chemoradiotherapy for advanced head and neck cancer — Analysis of a prospective, randomized trial

Objective: To study the efficacy of neo-adjuvant chemotherapy followed by radiotherapy in advanced head and neck cancer.Study design: Randomised, prospective study.Setting: Tertiary academic referral center.Patients: One hundred and eighty patients of advanced head and neck squamous cell carcinoma.Intervention: Patients were randomized into two arms. The study arm (CT-RT arm) received 3 cycles of anterior chemotherapy with Inj. Cisplatin 100 mg/m² on D₁ and Inj 5F.U. 700 mg/m² on D₁-D₄ at an interval of 21 days, followed by external radiation. The control arm (RT arm) received external radiotherapy only. The dose of Radiotherapy was 64 to 68 Gy in conventional fractionation.Results: Patients of CT-RT showed better tumour control locally than patients who received only RT. Toxicities were commoner in CT-RT arm but they were manageable. 5 year survival is higher in the CT-RT arm (21% vs 16%; p value> 0.05).Conclusion: Anterior chemotherapy with Cisplatin and 5F.U. is associated with good clinical response which is translated into increased survival along with acceptable toxicities.