Advanced Oral Cancer Patients Research Articles

Early Referral to Palliative Care for Advanced Oral Cancer Patients: A Quality Improvement Initiative in Oncology Center at All India Institute of Medical Sciences.

Objectives:Oral cancers have high epidemiologic burden in India, and most oral cancer patients at the All India Institute of Medical Sciences present in advanced stages. Their symptomatic needs are often not adequately addressed and the referrals to palliative medicine clinic are for severe pain or terminal stages. Using quality improvement methods, we aimed to provide early referral to palliative care for advanced oral cancer patients.Materials and Methods:Duration (number of days) between registration at the head-and-neck cancer clinic and referral to palliative medicine clinic at baseline and postinterventions. Interventions: Understanding current perceptions of oncologists for referral to palliative medicine clinic, educating them through departmental meetings, fostering clinician and patient-family awareness through pamphlets, defining process and screening guidelines for referral, including symptom burden charts in head-and-neck cancer clinic notes, soliciting regular feedback from oncologists at review meetings.Results:The number of days for the referral to the palliative medicine clinic decreased from an average of 48 days to 13 days in 6 months.Conclusion:A multicomponent intervention included oncologists and patients and families, education, workflow modification, standardized assessment, documentation, and clinician feedback, and succeeded in improving the timeliness of palliative care referrals of advanced oral cancer patients.

A Quality Improvement Project to Provide Early Referral to Palliative Care Clinic for Advanced Oral Cancer Patients (TH341A)

•Identify palliative care needs, referral timings and reasons for delay in referral to palliative care clinic for advanced oral cancer patients.•Develop, test and sustain interventions to provide early referral to palliative care clinic for advanced oral cancer patients. Recent literature affirms the benefits of early palliative care in advanced cancer patients. The prevalence of oral cancer is high in India and often patients present at advanced stages at the time of diagnosis. Bleak scope of curative treatment and high symptomatic burden detracts from the quality of life of these patients. The aim of this study was to provide early referral to a palliative care clinic for advanced oral cancer patients. This initiative was carried out at Dr B. R. Ambedkar, Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, India in collaboration with quality improvement leaders at Stanford University. A multidisciplinary team consisting of oncologists, surgeons, nurses, administrative staff, palliative care physicians and overseas quality improvement mentors was formed. Using A3 methodology, we applied improvement tools to understand the current situation. A cause and effect analysis revealed absence of referral guidelines and misalignment of what was deemed appropriate early referral as the major factors contributing to the practice of late referral. Our interventions were developing a standard, agreed upon, protocol for providing palliative care referral and consultation, creating awareness through pamphlets, educating oncologists and surgeons through weekly departmental meetings and documenting symptom burden in the medical record. The interventions were sustained by soliciting feedback from oncologists and surgeons during periodic departmental meetings, educating new oncologists and surgeons about referral protocols during their orientation program i.e. once in three months and by auditing patient referral data. Number of days from identification of advanced oral cancer to referral to palliative care clinic decreased from an average of 48 days at baseline to 13 days post-interventions. Early referrals to palliative care clinic are possible using a multidisciplinary team approach focusing on aligning expectations between oncologists, surgeons and palliative care professionals, modifying process maps and standardizing and documenting assessment.

Anlotinib is effective in patients with advanced oral cancer?

Oral cancer patients with recurrence or distant metastasis often present poor prognosis. Majority of advanced oral cancer patients suffer from treat-related adverse events and drug resistance. For those patients, the survival time and quality of life are urgent to be improved. Anlotinib, as a multi-targets tyrosine kinase inhibitor (TKI), has been demonstrated to be effective in many refractory tumors by inhibiting tumor angiogenesis and partial functions of tumor cells. In this paper, we performed CCK-8 assay, wound healing assay and transwell assay to explore the effect of anlotinib on human tongue squamous carcinoma Tca8113 cell line. Preliminary data indicated that anlotinib significantly inhibited Tca8113 cells proliferation, migration and invasion in vitro. Together, we proposed a hypothesis that anlotinib might be effective in prolonging survival time of patients with advanced oral cancer.

Caffeic Acid Phenethyl Ester Is a Potential Therapeutic Agent for Oral Cancer

Head and neck cancers, which affect 650,000 people and cause 350,000 deaths per year, is the sixth leading cancer by cancer incidence and eighth by cancer-related death worldwide. Oral cancer is the most common type of head and neck cancer. More than 90% of oral cancers are oral and oropharyngeal squamous cell carcinoma (OSCC). The overall five-year survival rate of OSCC patients is approximately 63%, which is due to the low response rate to current therapeutic drugs. In this review we discuss the possibility of using caffeic acid phenethyl ester (CAPE) as an alternative treatment for oral cancer. CAPE is a strong antioxidant extracted from honeybee hive propolis. Recent studies indicate that CAPE treatment can effectively suppress the proliferation, survival, and metastasis of oral cancer cells. CAPE treatment inhibits Akt signaling, cell cycle regulatory proteins, NF-κB function, as well as activity of matrix metalloproteinase (MMPs), epidermal growth factor receptor (EGFR), and Cyclooxygenase-2 (COX-2). Therefore, CAPE treatment induces cell cycle arrest and apoptosis in oral cancer cells. According to the evidence that aberrations in the EGFR/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling, NF-κB function, COX-2 activity, and MMPs activity are frequently found in oral cancers, and that the phosphorylation of Akt, EGFR, and COX-2 correlates to oral cancer patient survival and clinical progression, we believe that CAPE treatment will be useful for treatment of advanced oral cancer patients.

Jugular vein reconstruction by longitudinal constriction suture venoplasty and microvascular anastomosis

Objective To seek a new method for reconstructing bilateral intemrnal jugular vein invaded by metastasis lymph node in advanced oral cancer patients. Methods A combination of microvascular anastomosis and longitudinal constriction suture venoplasty was performed to reconstruct internal jugular vein. We resected the part of the bilateral internal jugular vein of advanced oral cancer patients invaded by metastasis lymph node and used the external carotid vein to reconstruct the internal jugular vein. A part of the vessel wall of the internal jugular vein could also be resected to reconstruct the vein. Longitudinal constriction suture venoplasty could slowly narrow the lumen diameter of the internal jugular vein. Thus, difference in anastomosis diameter should be avoided because it generates eddy currents and subsequently causes blood clots. A total of five advanced cases of oral squamous cell carcinoma were involved in this study. We performed bilateral radical neck dissection on all patients to reconstruct the internal jugular vein and observed their postoperative conditions. Results Postopera-tive follow-up of 5 months to 19 months was performed on all patients. Doppler or CT angiography and related tests showed no internal jugular vein thrombosis. No patient with facial edema, throat swelling, cerebral edema, and high intracranial pressure or other serious complications caused by blocked venous blood was observed. The one-year survival rate of five patients was 60% (3/5). Conclusion Microvascular anastomosis combined with longitudinal constriction suture venoplasty is a new method for reconstructing internal jugular vein. This method was proved successful and clinically feasible.

Delay in seeking specialized care for oral cancers: experience from a tertiary cancer center.

Advanced oral cancers are a challenge for treatment, as they require complex procedures for excision and reconstruction. Despite being occurring at a visible site and can be detected easily, many patients present in advanced stages with large tumors. Timely intervention is important in improving survival and quality of life in these patients. The aim of the present study was to find out the causes of delay in seeking specialist care in advanced oral cancer patients. A prospective questionnaire based study was done on 201 consecutive advanced oral squamous cancer patients who underwent surgery at our hospital. All patients had either cancer of gingivobuccal complex (GBC) or tongue and had tumors of size more than 4 cm (T3/T4) and were treatment naοve at presentation. Even though most patients observed abnormal lesions in their mouth, majority delayed the decision to visit a physician early. A significant percentage of patients (50%) also reported a delayed diagnosis by the primary care physician before being referred to a tertiary care center for definitive treatment. The average total duration from symptoms to treatment was 7 months. The main reasons of this delay in receiving treatment were due to patients themselves (primary delay) or due to time taken by the primary physician to diagnose the condition (secondary delay). Oral self-examination can be helpful in detecting oral cancers early.

Thermochemoradiotherapy using superselective intra-arterial infusionfor N3 cervical lymph node metastases of tongue cancer

A case of squamous cell carcinoma of the tongue with advanced N3 cervical lymph node metastases in an 80-year-old female is reported. The patient was treated with a combination of radiotherapy (2 Gy/day, total 60 Gy), superselective intra-arterial chemotherapy via a superficial temporal artery and a femoral artery (docetaxel, total 124 mg; cisplatin, total 135 mg), and four sessions of hyperthermia for cervical lymph node metastases. The tumor responded well to therapy, and 18-fluorodeoxyglucose uptake in both primary and neck lesions disappeared on positron emission tomography-computed tomography. The patient has shown no clinical or radiological evidence of local recurrence or distant metastases 6 years after the end of treatment. Advanced oral cancer patients with N3 cervical lymph node metastases are particularly difficult to treat and have a poor prognosis. This method of thermochemoradiotherapy seems a promising modality for patients with N3 cervical lymph node metastases of oral cancer.

Polymorphisms in GSTM1 and XPD genes predict clinical outcome in advanced oral cancer patients treated with postoperative radiotherapy

Polymorphisms in metabolic and DNA repair genes may alter protein function, consequently affecting patients' response to chemo/radiotherapy. We retrospectively assessed whether polymorphisms of glutathione-S-transferase genes GSTM1 (deletion), GSTT1 (deletion), GSTP1 (Ile105Val, rs1695), and DNA repair genes hOGG1 (Ser326Cys, rs1052133), XRCC1 (Arg194Trp, rs1799782, and Arg399Gln, rs25487), XPD (Asp312Asn, rs1799793, and Lys751Gln, rs13181) can predict clinical outcome in 187 oral squamous cell carcinoma patients treated with postoperative radiotherapy. The Cox proportional hazards model was used to evaluate the role of polymorphic genotypes on relapse-free (RFS) and disease-specific (DSS) survival. Deletion polymorphism of GSTM1 gene was significantly associated with DSS. The rs1799793 variant allele showed significant protection in both DSS and RFS. Significant increase in RFS but not in DSS was observed with polymorphic rs13181. The combined analysis of GSTM1 and XPD polymorphisms revealed favorable effect on survival. GSTM1 and XPD variant alleles, independently as well as in combination may serve as important predictors of clinical outcome in radiotherapy-treated OSCC patients.

P6. Improved survival among advanced oral cancer patients taking metformin for diabetes mellitus control

P6. Improved survival among advanced oral cancer patients taking metformin for diabetes mellitus control

P20 Survival predictors of locally advanced oral cancer patients receiving radiotherapy or plus chemotherapy – multivariate analysis including quality of life

P20 Survival predictors of locally advanced oral cancer patients receiving radiotherapy or plus chemotherapy – multivariate analysis including quality of life

O.334 Perforator flaps in head and neck reconstruction

Autogenous vascularized bone grafts in combination with microsurgical techniques have revolutionized mandibular reconstruction in oral cancer surgery. The vascularized bone graft carries its own blood supply, resists infection, and heals rapidly even in the irradiated bed. However, its use in advanced oral cancer patients is controversial due to the gloomy prognosis of these patients. Effective alloplastic materials such as titanium plate or tray for mandibular reconstruction is a reasonable alternative. These can easily be shaped and have sufficient structural rigidity to maintain the mandibular fragments in proper orientation. Likewise, it is a fast and reliable procedure which can obtain good oral function. However, its potential late exposure due to breakdown of overlying skin, especially after radiotherapy, is well documented. This paper discusses our experience to rescue the oral function after alloplastic material failure using the vascularized fibula osteocutaneous flap, in irradiated patients. All fibula osteocutaneous flaps survived. Symmetry and contour of the reconstructed mandible were judged to be good, and patients were able to eat without saliva drooling. Donor-site morbidity was also low. From this clinical study, we believe that in advanced oral cancer, the titanium plate or tray is a useful adjunct for immediate mandibular reconstruction after surgical resection. The vascularized bone graft should be reserved for patients with alloplastic material failure. This rationale can avoid subjecting the patient to an unnecessary extensive mandibular reconstructive procedure.

Patterns of Nodal Metastasis in Locally Advanced Oral Cancer Patients: Review of 268 Cases

Statement of the Problem: Neck dissection is an integral part of surgical treatment of oral cavity carcinoma. Knowledge of patterns of nodal spread of tumor from various subsites in oral cavity is mandatory to avoid morbidity of radical neck dissections. Most of the existing literature about neck nodal metastasis pertains to head and neck cancer as a whole group. This study describes the neck nodal metastasis pattern of tumors from different subsites in oral cavity along with the factors affecting the regional relapse. Materials and Methods: A retrospective analysis of 268 patients with squamous cell carcinoma of oral cavity treated between 1999 and 2003 was performed. Patients were treated with upfront surgery (primary tumor resection and neck dissection) with or without adjuvant radiotherapy. Supraomohyoid and modified radical neck dissection were performed in clinically N0 and N patients respectively. Patterns of nodal metastasis to neck (levels I to V) and regional nodal relapse were evaluated. Method of Data Analysis: The collected database was analyzed using SPSS-10.Apart from descriptive analysis, factors associated with relapse were determined. All calculations were performed at the confidence interval of 95%. Significance was calculated using the ‘t test’. Results: A total of 322 neck dissections were performed for tumors located in buccal (27%), alveolobuccal (23%), alveolus (17%), tongue (17%), retromolar trigone (8%), lip (6%) and floor of mouth (2%). Mean tumor size was 3.1 cms. Pathological nodal involvement was present in 40.6% of the patients (of them 50% had more than one node positive). Most common involvements were at levels I, II and III. Level IV and V accounted for 3.8% only. For buccal, alveolus, lip and retromolar trigone tumors, 97% of the nodal metastasis was confined to levels I, II & III. Levels III, IV and V involvement was comparatively higher for tumors in tongue and alveolobuccal area. Skip metastasis was present in only 4.5% of the node positive patients. Extranodal spread was present in 18%. A total of 16 patients (6%) had regional nodal relapse. Mean number of positive nodes in patients with regional relapse was 3.06 (p 0.0001). Other factors associated with regional relapse were presence of pathological nodal metastasis and extranodal spread. Conclusion: Patterns of neck nodal metastasis from oral cavity carcinoma is different from other areas of head and neck with most of the spread being to levels I & II and rarely to levels IV & V. Skip metastasis is uncommon. Presence of nodal metastasis and extranodal spread are significant risk factors for regional relapse. In view of low incidence of level IV & V involvement and skip metastasis, more conservative neck dissections are justified in the management of advanced oral cancer.

The rationale of mandible reconstruction in advanced oral cancer: alloplastic material versus autogenous vascularized bone graft

Autogenous vascularized bone grafts in combination with microsurgical techniques have revolutionized mandibular reconstruction in oral cancer surgery. The vascularized bone graft carries its own blood supply, resists infection, and heals rapidly even in the irradiated bed. However, its use in advanced oral cancer patients is controversial due to the gloomy prognosis of these patients. Effective alloplastic materials such as titanium plate or tray for mandibular reconstruction is a reasonable alternative. These can easily be shaped and have sufficient structural rigidity to maintain the mandibular fragments in proper orientation. Likewise, it is a fast and reliable procedure which can obtain good oral function. However, its potential late exposure due to breakdown of overlying skin, especially after radiotherapy, is well documented. This paper discusses our experience to rescue the oral function after alloplastic material failure using the vascularized fibula osteocutaneous flap, in irradiated patients. All fibula osteocutaneous flaps survived. Symmetry and contour of the reconstructed mandible were judged to be good, and patients were able to eat without saliva drooling. Donor-site morbidity was also low. From this clinical study, we believe that in advanced oral cancer, the titanium plate or tray is a useful adjunct for immediate mandibular reconstruction after surgical resection. The vascularized bone graft should be reserved for patients with alloplastic material failure. This rationale can avoid subjecting the patient to an unnecessary extensive mandibular reconstructive procedure.

Bipaddled, retrograde radial extended forearm flap with microarterial anastomosis for reconstruction in oral cancer

The design of a bipaddled, retrograde, radial artery forearm flap is described. Its utility in providing lining and cover for advanced oral cancer patients in five clinical cases is discussed and evaluated.