Survival patterns in patients with carcinoma base of tongue treated with external beam irradiation and salvage surgery

Objective

The current study was designed to assess the treatment results and survival in the patients with carcinoma of base of tongue that were treated with primary radiotherapy, radiotherapy with chemotherapy and salvage surgery when indicated.

Design

A prospective study was carried out in 78 cases of carcinoma of the base of tongue between 1995 and 1999.

Methods

The majority of cases belonged to stage IV 60/78 (76.92%) as per AJCC staging. Radiotherapy in the dose of 60 Gy was given primarily to the patients with stage III tongue base cancer. Patients with early stage IV cancer were given split course radiotherapy followed by assessment for surgery. For the patients with advanced stage IV disease with poor general condition, palliative radiotherapy of 24 Gy with or without palliative chemotherapy was given. 15 patients were subjected to salvage surgery in the form of radical neck dissection alone (8 cases), extended total laryngectomy with neck dissection (3 cases), extended total laryngectomy (2 cases) and extended supraglottic laryngectomy with RND in 2 cases.

Results

Two and 5 years Kaplan — Meier actuarial survival rates were 45% and 10% respectively with local control rates equivalent to survival rates. All surviving patients maintained good function and quality-of-life with few tolerable side effects.

Conclusions

External beam radiotherapy with salvage surgery results in satisfactory local and regional control in stage III and IV carcinoma base of tongue.     

<Emphasis Type="Italic">M6P/IGF2R</Emphasis>loss of heterozygosity in head and neck cancer associated with poor patient prognosis

Background

The mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) encodes for a multifunctional receptor involved in lysosomal enzyme trafficking, fetal organogenesis, cytotoxic T cell-induced apoptosis and tumor suppression. The purpose of this investigation was to determine if the M6P/IGF2R tumor suppressor gene is mutated in human head and neck cancer, and if allelic loss is associated with poor patient prognosis.

Methods

M6P/IGF2R loss of heterozygosity in locally advanced squamous cell carcinoma of the head and neck was assessed with six different gene-specific nucleotide polymorphisms. The patients studied were enrolled in a phase 3 trial of twice daily radiotherapy with or without concurrent chemotherapy; median follow-up for surviving patients is 76 months.

Results

M6P/IGF2R was polymorphic in 64% (56/87) of patients, and 54% (30/56) of the tumors in these informative patients had loss of heterozygosity. M6P/IGF2R loss of heterozygosity was associated with a significantly reduced 5 year relapse-free survival (23% vs. 69%, p = 0.02), locoregional control (34% vs. 75%, p = 0.03) and cause specific survival (29% vs. 75%, p = 0.02) in the patients treated with radiotherapy alone. Concomitant chemotherapy resulted in a better outcome when compared to radiotherapy alone only in those patients whose tumors had M6P/IGF2R loss of heterozygosity.

Conclusions

This study provides the first evidence that M6P/IGF2R loss of heterozygosity predicts for poor therapeutic outcome in patients treated with radiotherapy alone. Our findings also indicate that head and neck cancer patients with M6P/IGF2R allelic loss benefit most from concurrent chemotherapy.

     

Increased risk of stroke in young head and neck cancer patients treated with radiotherapy or chemotherapy

Background

Chemo-radiotherapy-induced carotid stenosis and cerebrovascular events in head and neck cancer patients can cause severe disability and death. We aimed to estimate the risk of stroke in such patients over a six-year follow-up period.

Patients and methods

The study cohort consisted of head and neck cancer patients (n = 10,172). Cox proportional hazard model was used to compare the stroke-free survival rate between the patients treated with radiotherapy or chemotherapy, surgery alone, and surgery with adjuvant therapy after adjusting for possible confounding factors.

Results

At the end of follow-up, 384 patients had strokes: 126 (4.3%) from the surgery alone group, 167 (3.8%) from the radiotherapy or chemotherapy group, and 91 (3.2%) from the surgery with adjuvant therapy (P = 0.222). Head and neck cancer patients aged less than 55 years treated with radiotherapy or chemotherapy conferred a 1.8-fold higher risk for stroke (95% CI, 1.22–2.56; P = 0.003) after adjusting for patient characteristics, co-morbidities, geographic region, urbanization level, and socio-economic status. There was no statistical difference in stroke risk between different treatment modalities in head and neck cancer patients aged 55 years and more.

Conclusions

Young head and neck cancer patients treated with radiotherapy or chemotherapy have higher risks for stroke. Different treatment strategies should be considered in such patients.     

Quimioterapia de inducción seguida de radioquimioterapia como alternativa a la laringuectomía en el tratamiento del cáncer de cabeza y cuello localmente avanzado

Objective

To evaluate survival in patients with loco-regional advanced head and neck cancer treated with induction chemotherapy and to assess possible larynx preservation in good responders.

Materials and methods

Between December 1997 and June 2000, patients (n=46) diagnosed as having advanced head and neck carcinoma were treated with induction chemotherapy (CT). This was followed by radiotherapy (RT) + CT if there had been complete response (CR) or partial response (RP) >80%; or followed by total laryngectomy and adjuvant RT if CR or PR was <80%.

Results

Of the 46 patients studied, 57 (80%) had CR, 10% had PR and 10% had no response or disease progression (DP). Median survival was 33%, followup was of 50 months during which the overall survival was 36%, disease-free survival (DFS) was 60% and loco-regional control was 51%.

Conclusion

RT-CT resulted in high rates of disease resolution and speech preservation in patients who, traditionally, had poor clinical and functional outcomes.     

Aktuelle Aspekte der radioonkologischen Behandlung lokal fortgeschrittener Kopf-Hals-Tumoren

Background

Concomitant chemo-irradiation is one of the main components in the treatment of locally advanced head and neck cancer. Over the last decade the development of intensity modulated radiotherapy (IMRT) has been rapidly implemented in the treatment of patients with head and neck cancer.

Objectives

Treatment recommendations for locally advanced head and neck cancer are given based on the results of radio-oncological meta-analyses. Strategies for organ and function preservation as well as human papillomavirus (HPV) positive tumors are discussed. Recent technological progress in radiation oncology will be briefly explained.

Materials and methods

The study included research and analysis of the literature and published results of clinical trials and meta-analyses.

Results and conclusion

The concomitant platinum-based chemo-irradiation is the state of the art treatment for locally advanced head and neck cancer. If there are contraindications for concomitant chemo-irradiation the fractionation schedule (hyperfractionation) should be changed. Induction chemotherapy (iCT) is seen at the moment as experimental and should only be used in controlled trials. Concerning HPV positive tumors there is still no evidence to support changes in the standard treatment regimen.     

Competing causes of death in patients with locoregionally advanced head and neck cancer treated with concomitant boost radiation plus concurrent weekly cisplatin

Background

This study analyzes the morbidity and the contribution of different causes of death to the outcome of patients with locally advanced head and- neck cancer after weekly cisplatin plus concomitant boost accelerated radiation treated in our center.

Materials and methods

Ninety-four patients with locally advanced head and neck carcinoma were included in this phase II trial consisting of concomitant boost radiation plus concurrent weekly cisplatin. The 43 patients treated in our centered with long-term follow-up were analyzed. Patients received radiotherapy with a concomitant boost scheme (1.8 Gy on days 1–40 and 1.5 Gy boost on days 25–40 with a total dose of 72 Gy) and concurrent cisplatin, 40 mg/m² weekly, for the first 4 weeks.

Results

Most patients (93 %) received both radiation and complete chemotherapy according to protocol. Severe late toxicity presented were subcutaneous (5 %), larynx (2 %) and esophagous (5 %). Grade I–II late toxicity included mainly xerostomy (30 %), skin (16 %) and mucosal (16 %) toxicity. With a median follow-up of 95 months (9–135), the median overall survival and progression-free survival were 26 and 19 months, respectively (95 % CI 1–52; and 95 % CI 0–45); 60 % of the patients died because of head and neck cancer and 12 % of a second neoplasm, while 27 % of non-cancer patients died.

Conclusions

Patients with locoregionally advanced head and neck cancer treated with concomitant boost accelerated radiation plus chemotherapy show significant risks of mortality from causes other than disease progression.     

The role of radiotherapy in the management of progressive glioblastoma

Question

Can re-irradiation (by using conventional radiotherapy, fractionated radiosurgery, or single fraction radiosurgery) be used in patients with progressive glioblastoma multiforme after the first adjuvant combined multimodality treatment with radiation and chemotherapy?

Target population

These recommendations apply to adult patients with progressive glioblastoma after first line combined multimodality treatment with chemotherapy and radiation.

Recommendations

Level III

When the target tumor is amenable for additional radiation, re-irradiation is recommended as it provides improved local tumor control, as measured by best imaging response. Such re-irradiation can take the form of conventional fractionation radiotherapy, fractionated radiosurgery, or single fraction radiosurgery.

Level III

Re-irradiation is recommended in order to maintain or improve a patient’s neurological status and quality of life prior to any further tumor progression.     

Temporal lobe necrosis: a dwindling entity in a patient with nasopharyngeal cancer after radiation therapy

Purpose

The pectoralis major myocutaneous flap (PMMF) is a commonly used flap in reconstructive head and neck surgery, but in literature, the flap is also associated with a high incidence of complications in addition to its large bulk. The purpose of the study is the evaluation of the reliability and indication of this flap in reconstructive head and neck surgery.

Patients and methods

The records of all patients treated with a PMMF between 1998 and 2009 were systematically reviewed. Data of recipient localization, main indication, and postoperative complications were analyzed.

Results

The male to female ratio was 17:3, with a mean age of 60 years (45-85). Indications in 7 patients were recurrence of a squamous cell carcinoma, in one case an osteoradionecrosis and in 12 cases an untreated squamous cell carcinoma. In 6 male patients (30%), a complication appeared leading to another surgery.

Conclusion

The PMMF is a flap for huge defects in head and neck reconstructive surgery, in particular when a bulky flap is needed in order to cover the carotid artery or reconstructive surgery, but the complication rate should not be underestimated in particular after radiotherapy.     

Chronological shifts and changing causes of death after radiotherapy for early-stage oral cancer

Background

Following recent improvements in the curability of oral cancer, chronological shifts and changes in the causes of death after treatment have been observed. We conducted a review of the post-treatment causes of death following radiotherapy for oral cancers.

Materials and methods

The medical records of 966 patients with early-stage (stage I and II) oral cancer treated at our institute between 1980 and 2001 were reviewed, and the chronological shifts and changes in the causes of death after radiotherapy were assessed.

Results

Of the 966 patients enrolled in this study, 365 have died to date. Two hundred and eleven patients died of their primary malignancy; 193 of these deaths occurred within 5 years of treatment for the primary oral cancer. The second most frequent cause of death was second primary cancer (n = 90). Twenty-three patients with head and neck cancers and 18 patients with esophageal cancers died within 10 years of radiotherapy, and six patients with lung cancers died after more than 10 years.

Conclusion

Within the first 5 years following treatment, the major cause of death was the primary oral cancer. After 5–10 years, a second primary cancer, such as head and neck cancer or esophageal cancer, became the leading cause of death. Over a 10-year period, the proportion of deaths from a second primary cancer in the lung was significant. We have demonstrated that there are chronological shifts and changes in the causes of death following treatment for early-stage oral cancer.     

Antiemetic effects of granisetron and dexamethasone combination therapy during cisplatin-containing chemotherapy for head and neck cancer: dexamethasone dosage verification trial

Background

Chemotherapy-induced nausea and vomiting (CINV) remains a significant problem for patients and is associated with a substantial deterioration in quality of life; appropriate use of antiemetic drugs is crucial in maintaining the quality of life in patients undergoing chemotherapy.

Methods

This randomized, crossover trial evaluated the antiemetic efficacy and safety of 8 mg per day (low-dose) and 16 mg per day (standard-dose) dexamethasone, in combination with the 5-HT₃ receptor antagonist granisetron, in 36 patients receiving cisplatin (CDDP)-containing chemotherapy for head and neck cancer. Following chemotherapy, the antinausea/vomiting inhibition rate for each dexamethasone dose was measured.

Results

During the 24-h period following administration of chemotherapy (acute phase), the antinausea/vomiting inhibition rates (no nausea and no episodes of vomiting) for 8 mg and 16 mg dexamethasone were comparably high (58.3% and 63.8%, respectively; P = 0.8092). Similar results were seen on days 2–5 following chemotherapy. Efficacy during the acute phase, based on the number of instances of vomiting and degree of nausea, was also comparably high for the two dexamethasone doses (overall efficacy rates were 94.4% and 88.8%, respectively, for 8 mg and 16 mg dexamethasone; P = 0.7637). Both doses maintained an 80% or higher response rate until day 3, and neither dose produced severe side effects.

Conclusion

The results suggest that granisetron and dexamethasone combination therapy is useful in controlling acute and delayed nausea and vomiting induced by CDDP-containing chemotherapy for head and neck cancer. Furthermore, 8 mg and 16 mg dexamethasone have equivalent antiemetic efficacy.     

Management of unresectable head and neck cancers — a retrospective analysis at a rural medical college of India

Objective

To study the natural course of disease in patients of advanced squamous cell carcinoma of head and neck (SCCHN) admitted in a rural tertiary hospital and to formulate an acceptable protocol of management and their prognosis.

Study design

A 5-year retrospective analysis of patients of advanced SCCHN attended in the department of Radiotherapy and admitted at department of ENT at B. S. Medical College, Bankura, West Bengal were analyzed for the present study.

Setting

B. S. Medical College, Bankura at West Bengal, which is a rural medical college and act as tertiary referral, center for three district of West Bengal namely Midnapur, Purulia, Bankura, part of Burdwan and adjoining area of Jharkhand state.

Patients

We investigated 100 patients in our hospital who presented with advanced and in-operable stage of SCCHN.

Eligibility criteria

Biopsy proved cases of SCCHN in stage III, stage IVA and stage IVB which is surgically unresectable and without any past history of radiotherapy and chemotherapy were included in this study.

Key demographic features

Eighty-nine men and 11 female with advanced SCCHN were included in this study. Their median age was 48 years (36–78 years) with a median weight of 44 kg and median Karnofsky score 70.

Interventions

Different types of palliative surgical intervention like Ryles’ tube insertion (16%), feeding jejunostomy (11%), tracheostomy (60%) and arterial ligation (2%) was done to relieve the symptoms. Forty-three patients received chemoradiation and 22 patients received only radiotherapy. Best supportive care was provided to 35 patients.

Outcome

Twenty-nine percent of patients had partial response in terms of disease control and none had complete response.

Conclusion

Symptomatic relief of respiratory obstruction, dysphagia and pain constitute the mainstay of treatment in the present study. A short course of radiotherapy is found to be effective in control of symptoms and helps to improve the quality-of-life. Complete response to therapy in advanced head and neck squamous cell carcinoma with a poor nutritional status is very difficult to achieve.     

High-risk endometrial cancer may be benefit from adjuvant radiotherapy plus chemotherapy

Objective:To present patterns of practice and outcomes in the adjuvant treatment of intermediate-and high-risk endometrial cancer.Methods:Retrospective data on 224 women with intermediate-risk and high-risk endometrial cancer from 1999 to 2006 were reviewed.All patients underwent surgical staging.Patterns of adjuvant treatment,consisting of pelvic radiotherapy,chemotherapy,and radiotherapy plus chemotherapy,were assessed.The 3and 5-year disease-specific survival(DSS) rates were calculated using the Kaplan-Meier method.Results:The difference in 5-year DSS rate was statistically significant between adjuvant group and non-adjuvant group(80.65% vs.63.80%,P=0.040).In 110 high-risk patients who underwent adjuvant treatment,both 5-year DSS rate and recurrent rate were significantly different in combined radiotherapy and chemotherapy group compared with radiotherapy alone and chemotherapy alone groups(DSS rate,P=0.049;recurrent rate,P=0.047).In 83 intermediate-risk women who underwent adjuvant treatment,there was no significant difference in 5-year DSS rate and recurrence rate among the combined radiotherapy and chemotherapy,radiotherapy alone and chemotherapy alone groups(DSS rate,P=0.776;recurrent rate,P=0.937).Conclusions:Adjuvant radiotherapy plus chemotherapy is associated with a higher 5-year DSS rate and lower recurrence rate compared with radiotherapy alone and chemotherapy alone in high-risk endometrial cancer patients.Patients with intermediate-risk endometrial cancer may be not likely to benefit from adjuvant combined radiotherapy and chemotherapy.     

Verbesserte Behandlungschancen durch molekulares Targeting in der Radioonkologie

Context

Intensity-modulated and biologically guided high precision radiotherapy determine today’s modern radio-oncology. Relatively unexploited, however, is the administration of targeted molecular drugs for radiosensitization of malignant solid tumors.

Objective

The current status of these novel treatment strategies given simultaneously to radiotherapy will be discussed with respect to preclinical and clinical data.

Material and methods

Research and analysis of the literature and clinical trials.

Results

Through better understanding of tumor biology, potential target molecules for pharmacological inhibitors and antibodies were identified of which a selected number have been evaluated in preclinical and clinical studies. Locoregional tumor control and overall survival were increased, for example after radiotherapy by antibody-mediated inhibition of the epidermal growth factor receptor (EGFR) in radiotherapy patients suffering from head and neck cancer. Selected antibodies are, in contrast to pharmacological inhibitors, approved for certain tumor entities in combination with radiotherapy or radiochemotherapy.     

p53 in head and neck cancer: Functional consequences and environmental implications of TP53 mutations

Background

Chemoradiotherapy for head and neck cancer (SCCHN) is challenging in elderly, multi-morbid patients. Radioimmunotherapy (RIT) with cetuximab provides an option to enhance efficacy of radiotherapy without increased toxicity. We present a single-centre experience of RIT these patients.

Methods

Toxicity and outcome was retrospectively analysed in patients treated with radiotherapy and cetuximab between 2006 and 2009. Treatment response was analysed at first follow-up, outcome was estimated using Kaplan-Meier analyses.

Results

73 patients with primary/recurrent SCCHN were treated (re-irradiation: 22 patients). CTC grade 3 allergic reactions occurred in 4 patients, grade 3 acneiforme skin reactions leading to discontinuation of cetuximab in 3 patients. Overall response rate was 59,4%, median locoregional and overall progression-free survival (PFS) was 18 and 15 months, overall survival (OS) 18 months.

Conclusion

RIT is a feasible treatment option for elderly and multi-morbid patients with promising therapeutic activity. Long-term disease control can also be achieved in patients receiving RIT for re-irradiation.     

Multicenter phase II trial of preoperative chemoradiotherapy with S-1 for locally advanced oral squamous cell carcinoma

Purpose

We evaluated whether preoperative chemotherapy with S-1 and concurrent radiotherapy is feasible and efficacious in the treatment of advanced oral squamous cell carcinoma.

Methods

Participants comprised 39 patients with oral carcinoma (stage III, n = 15; stage IVA, n = 24). All patients received a total radiation dose of 40 Gy, in once-daily 2-Gy fractions, and received S-1 at 65 mg/m²/day for 5 consecutive days, over 4 consecutive weeks with concurrent radiotherapy.

Results

Hematological toxicity was mild and reversible. The most common non-hematological toxicity was grade 3 mucositis, but this was transient and tolerable. Radical surgery was performed for 37 patients, with the remaining 2 patients declining the surgery. Postoperatively, local failure developed in 1 patient, and neck failure in 2 patients. Distant metastases were identified in 4 patients. At a median follow-up of 38.0 months (range 23–88 months), locoregional control, disease-specific survival, and overall survival rates at 3 years were 91.5, 83.8, and 83.8 %, respectively.

Conclusion

Concurrent administration of S-1 and radiotherapy combined with surgery offers a well-tolerated method of successfully treating advanced oral squamous cell carcinoma. The locoregional control rate remains high even at 3 years of follow-up, and no serious adverse effects have been encountered.     

Nutrient-based dietary patterns of head and neck squamous cell cancer: a factor analysis in Uruguay

Objective

The aim of this study was to investigate the association between nutrient-based dietary patterns and squamous cell cancers of the head and neck.

Methods

We used a case–control study which included 548 cases and 548 controls. From these participants, we derived 23 nutrients and they were then submitted to a factorability analysis in order to conduct a principal component factor analysis.

Results

We were able to identify four nutrient-derived patterns. The first pattern (meat-based pattern) was positively associated with squamous cell cancer of the head and neck (OR 2.85, 95 % CI 1.81–4.15), whereas the third pattern (fruit-based) was strongly protective (OR 0.43, 95 % CI 0.27–0.63). The other nutrient patterns were also significantly associated with head and neck squamous cell carcinoma with minor ORs.

Conclusion

Both patterns suggest that red meat and fruits are major factors in the etiology of head and neck squamous cell cancer, replicating previous studies in the field.     

Spinal metastasis in head and neck cancer

Background

The incidence of head and neck cancer is relatively low in developed countries and highest in South East Asia. Notwithstanding advances in surgery and radiotherapy over the past several decades, the 5-year survival rate for head and neck cancer has stagnated and remains at 50?C55%. This is due, in large part, to both regional and distant disease spread, including spinal metastasis. Spinal metastasis from head and neck cancer is rare, has a poor prognosis and can significantly impede end-stage quality of life; normally only palliative care is given. This study aims to conduct a systematic review of the evidence available on management of spinal metastasis from head and neck cancer and to use such evidence to draw up guiding principles in the management of the distant spread.

Methods

Systematic review of the electronic literature was conducted regarding the management of spinal metastasis of head and neck malignancies.

Results

Due to the exceptional rarity of head and neck cancers metastasizing to the spine, there is a paucity of good randomized controlled trials into the management of spinal metastasis. This review produced only 12 case studies/reports and 2 small retrospective cohort studies that lacked appropriate controls.

Conclusion

Management should aim to improve end-stage quality of life and maintain neurological function. This review has found that radiotherapy +/? medical adjuvant is considered the principle treatment of spinal metastasis of head and neck cancers. There is an absence of a definitive treatment protocol for head and neck cancer spinal metastasis. Our failure to find and cite high-quality scientific evidence only serves to stress the need for good quality research in this area.     

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.     

A matched-pair comparison of intensity-modulated radiation therapy with cetuximab versus intensity-modulated radiation therapy with platinum-based chemotherapy for locally advanced head neck cancer

Purpose

We retrospectively compared the efficacy of intensity-modulated radiotherapy (IMRT) and cetuximab (IMRT/cetuximab) versus IMRT and platinum-based chemotherapy (IMRT/platinum) for locally advanced head neck squamous cell carcinoma (LAHNSCC).

Methods

Thirty-one IMRT/cetuximab patients were matched 1:2 with 62 IMRT/platinum patients according to primary site and clinical stage. The primary endpoint was locoregional recurrence (LRR), and secondary endpoints included distant metastasis (DM), cause-specific survival (CSS), and overall survival (OS).

Results

Because of inherent selection bias, the IMRT/cetuximab cohort was significantly older and with a higher Charlson Comorbidity Index. IMRT/cetuximab and IMRT/platinum did not have significantly different LRR and DM (33 vs. 23 % at 2 years, P = 0.22; 17 vs. 11 % at 2 years, P = 0.40; respectively). IMRT/cetuximab had significantly worse CSS and OS (67 vs. 84 %, P = 0.04; 58 vs. 83 %, P = 0.001; respectively). However, for the subset of elderly patients ≥65 years old, there is no difference between the two cohorts for all endpoints (all P = NS).

Conclusion

IMRT/platinum should remain the preferred choice of chemoradiotherapy for LAHNSCC, but IMRT/cetuximab may be a reasonable alternative for elderly patients.