Interstitial photodynamic therapy as salvage treatment for recurrent head and neck cancer

Interstitial photodynamic therapy (IPDT) is a technique for applying photodynamic therapy (PDT) to internal tumours using light delivered via fibres inserted percutaneously. This phase I-II study assessed the safety and efficacy of IPDT for patients with persistent or recurrent head and neck cancer unsuitable for further treatment with surgery, radiotherapy or chemotherapy, recruited for 'last hope' salvage treatment. Patients were sensitised with 0.15 mg kg(-1) mTHPC (meso-tetrahydroxyphenyl chlorin) 4 days prior to light delivery from fibres inserted directly into the target tumour (20 J per site at 652 nm) under image guidance. In all, 45 patients were treated. Nine achieved a complete response. Five are alive and free of disease 10-60 months later. Symptomatic relief (mainly for bleeding, pain or tumour debulking) was achieved in a further 24. The median survival (Kaplan-Meier) was 16 months for the 33 responders, but only 2 months for the 12 nonresponders. The only serious complication was a carotid blow out 2 weeks after PDT. No loss of function was detected in nerves encased by treated tumours. Interstitial photodynamic therapy provides worthwhile palliation with few complications and occasional long-term survivors for otherwise untreatable advanced head and neck cancers. It is a treatment option worth adding to those available to integrated head and neck oncology teams.     

Patients with head and neck cancer prefer individualized cognitive behavioural therapy

Cognitive behaviour therapy (CBT) is a widely practiced and approved form of psychotherapy for many psychosocial difficulties. As the efficacy of CBT is recognized, its demand has increased and today exceeds the availability of qualified practitioners. Therefore, the effectiveness of delivering CBT using less labour-intensive modes than individualised therapy has been explored. These include group therapy, bibliotherapy and computer assisted therapy. Given the UK Government's impetus towards patient choice and involvement in the planning of healthcare, it was thought essential to ascertain the preferred delivery mode of patients with head and neck cancer for a CBT based intervention. Therefore, a small retrospective cohort (n= 28) of patients following treatment for head and neck cancer were sent postal questionnaires to ascertain their preferences on mode of CBT delivery. Simultaneously, the views of accredited cognitive behaviour therapists (n= 14) were determined on the optimal mode of CBT delivery to these patients. Findings indicated that patients preferred the more individualized mode of CBT delivery, namely one-to-one therapy, followed closely by bibliotherapy, with group format being the least preferred option. Professionals concurred with patients, in that one-to-one interaction was considered an optimal mode of CBT delivery, but professionals considered it equal to group therapy.     

Global and health-related quality of life after intensity-modulated radiation therapy for head and neck cancer

This study aims to evaluate the current literature regarding the effects of conventional radiation therapy (CRT) versus intensity-modulated radiation therapy (IMRT) on global quality of life (QoL) among patients treated for head and neck cancer. A PubMed literature review was performed. Only articles comparing global QoL scores in head and neck cancer patients treated with CRT versus IMRT were included. Studies were scrutinized for methodology, level of evidence and limitations. Outcomes were evaluated for external validity, level of evidence and applicability. Between 2005 and 2012, 14 eligible studies (six prospective, two randomized controlled trials) were identified. Although all presented data comment on the advantages of IMRT, differences in study design made comparisons difficult. The vast majority of these were also limited by relatively small sample sizes and heterogeneity with respect to patient and treatment-related characteristics. Although more robust evidence is needed in the future, the published data reasonably support the benefits of IMRT as compared with CRT (either 2D or 3D) in improving QoL, beginning at approximately 3–6 months post-treatment, and possibly potentiating with time up to 2 and 3 years.     

Molecular therapy of head and neck cancer

Aberrant expression of growth factor receptor systems and dysregulation of the downstream cell signalling molecules have been reported in a wide range of epithelial tumours including head and neck cancer. In some cases, such alterations have been associated with a poor prognosis. In the past 25 years, several antigen specific monoclonal antibodies (mAbs, mouse, chimeric, humanized and human versions), and small molecule kinase inhibitors have been developed that are at different stages of preclinical and clinical developments. Some of these agents (e.g. Herceptin, Iressa, cetuximab, avastin) have already been approved for the treatment of epithelial tumours and may also have potential in the treatment of head and neck cancer patients. This review discusses, the development and potential of these antigen specific agents, in particular the human epidermal growth factor receptor (EGFR) inhibitors, either as a single agent or in combination with other EGFR inhibitors, biological agents (e.g. inhibitors of cycloogenase-2, angiogenesis, insulin like growth factor-I receptor and others), and conventional forms of therapy in the prevention and treatment of head and neck cancer. From preclinical and clinical studies with some of these compounds, it is evident that further detailed studies of biopsies from cancer patients are needed in order to identify markers that can be used not only in the selection of the specific population of cancer patients who would benefit from such antigen specific therapeutic strategies, but also those factors which are responsible for the poor response and the development of a phenotype resistance to such inhibitors. The results of such studies could in turn facilitate the widespread use of such agents in the treatment of a wide range of human cancers including head and neck cancer.     

Combination chemotherapy as induction therapy for advanced resectable head and neck cancer

Fifty-four previously untreated patients with locally advanced resectable squamous cell carcinoma of the head and neck (SCCHN) were enrolled into a prospective randomized controlled trial to evaluate whether induction chemotherapy improves the disease-free survival compared to the standard treatment (surgery + radiation). Thirty patients received chemotherapy, which consisted of cisplatin 20 mg/m² day 1–5, bleomycin 10 mg/m², continuous infusion from day 3–7, and methotrexate 40 mg/m² given on day 15 and day 22. The cycle was repeated on day 29 for two cycles. Twenty patients completed chemotherapy courses. Overall response rate was 77% (23 of 30). No survival improvement was observed. Kaplan-Meier analysis indicated survival (and 95% confidence interval) at 3 years was 57% (29%-84%) for the control group and 60% (34%-87%) for the chemotherapy group, and 57% (29%-84%) and 45% (12%-78%) at 4 years (P = 0.736). However, patients who had a complete response were significantly better in terms of long-term survivors (5 of 7 patients were still alive), in contrast to patients who had partial responses among whom only 4 of 16 were alive. Toxicities of this induction protocol are tolerable; one chemotherapy-related death occurred from profound thrombocytopenia. If efforts in determining a chemotherapy-sensitive patient were successfully established, along with a better sequence and the discovery of new and safter drugs, survival of SCCHN should be much improved.     

光动力治疗消化道和头颈部肿瘤的临床观察

目的　探讨光动力疗法治疗消化道和头颈部肿瘤的疗效和安全性。方法　选取消化道肿瘤９例、头颈部复发转移癌７例行光动力治疗,其中早期４例,晚期１２例。具体治疗：静脉输注血卟啉３～５ｍｇ／ｋｇ,４８～７２ｈ在肿瘤表面或瘤体内行激光照射（输出波长６３０ｎｍ,输出功率６００～８００ｍＷ,能量密度为２００～３００Ｊ／ｃｍ２）。根据治疗后肉眼及内镜观察、Ｂ超和ＣＴ检查肿瘤缩小及症状缓解情况评价疗效。结果　所有患者治疗后随访１０～３９个月。４例早期患者均获ＣＲ,随访期间无复发;１２例晚期患者,获ＳＲ７例,ＭＲ４例,ＮＲ１例。全组患者的总有效率为９３.７％。主要毒副反应为暴露部位皮肤肤色加深,无严重并发症。结论　光动力疗法对于早期病灶局限的恶性肿瘤可达到局部根治的作用,对于晚期病例也能缓解症状并改善生存质量。     

A nomogram to predict loco-regional control after re-irradiation for head and neck cancer

Background and purpose

Loco-regionally recurrent head and neck cancer (HNC) in the setting of prior radiotherapy carries significant morbidity and mortality. The role of re-irradiation (re-RT) remains unclear due to toxicity. We determined prognostic factors for loco-regional control (LRC) and formulated a nomogram to help clinicians select re-RT candidates.

Material and methods

From July 1996 to April 2011, 257 patients with recurrent HNC underwent fractionated re-RT. Median prior dose was 65 Gy and median time between RT was 32.4 months. One hundred fifteen patients (44%) had salvage surgery and 172 (67%) received concurrent chemotherapy. Median re-RT dose was 59.4 Gy and 201 (78%) patients received IMRT. Multivariate Cox proportional hazards were used to identify independent predictors of LRC and a nomogram for 2-year LRC was constructed.

Results

Median follow-up was 32.6 months. Two-year LRC and overall survival (OS) were 47% and 43%, respectively. Recurrent stage (P = 0.005), non-oral cavity subsite (P < 0.001), absent organ dysfunction (P < 0.001), salvage surgery (P < 0.001), and dose >50 Gy (P = 0.006) were independently associated with improved LRC. We generated a nomogram with concordance index of 0.68.

Conclusion

Re-RT can be curative, and our nomogram can help determine a priori which patients may benefit.     

Experiences with intra-arterial chemotherapy for head and neck cancer

During the 10-year period from 1966-1975, 250 patients with various head and neck cancers were treated by intra-arterial chemotherapy using single agents or various combinations. Only 15 patients showed response of I-C category according to Karnofsky's criteria, and 100 patients had I-B response. Another 100 patients showed I-A category of response and 35 patient had progressive disease out of which 5 patients exhibited excessive toxicity to drugs, eventually succumbing to it. A majority of patients in nonresponding (O-O) category and I-A category were earlier treated by radiotherapy, and intra-arterial chemotherapy was given for recurrent disease. The responses were relatively good whenever chemotherapy was given as a primary treatment before surgery and radiotherapy. Again response was additive when chemotherapy was given concurrently with radiotherapy.     

Concurrent chemotherapy and radiotherapy for head and neck cancer

Head and neck cancer is best managed in a multidisciplinary setting. Surgery, radiation therapy, chemotherapy and, more recently, biologic therapy are often employed in various combinations in an attempt to eradicate both clinically apparent and occult disease. The goals of treatment include maximizing tumor control while maintaining function and quality of life. Most patients present with locally advanced disease, and multimodality organ-conserving therapy is often employed for these patients based on the results of multiple Phase III clinical trials. This article focuses on the rationale and evidence supporting the use of concurrent chemotherapy and radiation therapy in the management of locally advanced head and neck cancers.     

Rehabilitation problems of head and neck cancer patients.

Head and neck cancer and its treatment result in varying degrees of disability affecting various organ systems. Ideal treatment of such patients requires a unit capable of managing problems in the areas of: Reconstructive surgery, maxillofacial prosthodontia, dentistry, deglutition disorders, and psychological, social, and vocational rehabilitation. Provision of such facilities in an integrated manner will give the patient the optimal chance for rehabilitation from the complex disabilities occurring in head and neck cancer.     

A population-based study of therapy and survival for patients with head and neck cancer treated in the community

BACKGROUND:

The objective of this study was to examine patterns of care and survival in a population‐based sample of patients with head and neck cancer (HNC) who were treated in the community or in hospitals that had residency training programs.

METHODS:

Data from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program were used to sample 1317 patients aged ≥20 years with invasive squamous HNC who were diagnosed during 2004 and who had vital status available through 2008.

RESULTS:

Treatment and survival were influenced by tumor site and disease stage. Patients who had stage I/II cancer of the oral cavity generally underwent surgery; patients with stage III oral cavity disease underwent surgery and received radiation; and patients with stage IV oral cavity disease underwent surgery and received chemoradiation. Patients with early stage cancer of the oropharynx either underwent surgery or received radiation and chemotherapy, and patients with late/unstaged oropharyngeal disease primarily received radiation and chemotherapy. Patients with early stage cancer of the larynx mainly received radiation alone, and patients with late stage laryngeal disease generally received chemoradiation. Cisplatin‐based regimens were used most frequently. Overall, taxanes were used in 32% of regimens, and cetuximab was used in <3% of regimens. Patients aged ≥50 years, those with a Charlson comorbidity score ≥1, those with stage IV disease, and those with cancer located in the oral cavity or larynx had poorer survival. Although facilities with residency training programs treated more black patients and more patients with late stage disease, when adjusted for other factors, survival rates were similar to those reported in facilities with no such programs.

CONCLUSIONS:

Therapy generally followed accepted standards for 2004. Findings in particular tumor sites and stages may reflect the variability that still exists for the treatment of HNC. The use of taxanes and cetuximab is expected to increase based on new evidence of benefit. Reducing treatment‐related toxicities and long‐term functional deficits will be critical and especially important with the increase in human papillomavirus‐related cancers. In addition, further attempts to improve survival for older patients are needed. Cancer 2012. © 2012 American Cancer Society.     

Advances in radiation therapy of head and neck cancer

Head and neck cancer is the fifth most common cancer in the USA. Although there have been major improvements in surgical and radiation techniques, the overall survival has not changed significantly in the last decade. The major changes occurring in recent years have been in the ability to preserve organs and to improve quality of life. The advances in radiation therapy include 3D conformal radiotherapy, intensity-modulated radiotherapy and, more recently, imaging-guided radiotherapy. In advanced head and neck cancer the addition of chemotherapy to radiation has concomitantly improved survival and facilitated higher rates of organ preservation. Clinical trials are needed to develop better strategies customized to subgroups defined by individual biological risk and imaging findings.     

Chemotherapeutic management of head and neck cancer

The use of chemotherapy in patients with head and neck cancer is increasing. In patients with recurrent head and neck cancer, a large number of chemotherapeutic drugs have shown antitumor activity. These drugs are discussed, and factors which influence response rate and survival are examined. New agents and treatment, including specific agents for combination chemotherapy, are presented.There has been a search for new treatment or procedures in patients with previously untreated and locally advanced cancer of the head and neck. The results, including studies of combined modality therapy and chemotherapy after surgery, are discussed.Chemotherapy in tumor of the salivary glands is briefly discussed, followed by an examination of intraarterial therapy.     

Local control in advanced head and neck cancer by combined modalities of treatment

From July 1979 to January 1983, 20 patients with locally advanced head and neck cancer were treated with a combination of chemotherapy and irradiation with or without surgery. A majority of the patients were in the age range of 45 to 54 years. Eighty-five percent of the patients were male. Seventy-five percent of the patients had oral cavity lesions, the tongue being the most common site. Eighty percent of the patients had T₄ lesion and 35% had N₃ disease in the neck. A majority of the patients had combination chemotherapy, including bleomycin, methotrexate, and cis-platinum (BMP). All patients received irradiation with megavoltage equipment and 55% of patients received a dose of 5,000 to 6,000 rads in 5–6 weeks time. The tumor was converted to be resectable in ten patients. Nine patients (45%) had the neck and primary tumor completely controlled, while six patients (30%) had partial control. Six of the ten patients who had resection had the tumor controlled at the primary site and neck. The median duration of follow-up is 12 months (range, 4–32 months). The median survival of the whole group of patients is 12.5 months. A brief review of the current literature is also done in this paper.     

Intensity-modulated radiotherapy for recurrent and second primary head and neck cancer in previously irradiated territory

Purpose

To evaluate re-irradiation using IMRT for recurrent and second primary head and neck cancer in previously irradiated territory.

Materials and methods

Between 1997 and 2008, 84 patients with recurrent and second primary head and neck cancer were treated with IMRT to a median dose of 69 Gy. Median time interval between initial radiotherapy and re-irradiation was 49.5 (5.2-298.3) months. Salvage surgery preceded re-irradiation in 19 patients; 17 patients received concurrent chemotherapy.

Results

Median follow-up of living patients was 19.8 (1.9-76.1) months. Five-year locoregional control and overall survival were 40% and 20%, respectively. Five-year disease-specific survival and disease-free survival were 29% and 15%, respectively. Stage T4 (p = 0.015), time interval between initial treatment and re-irradiation (p = 0.011) and hypopharyngeal cancer (p = 0.013) were independent prognostic factors for worse overall survival in multivariate analysis. Twenty-six and 11 patients developed Grade ?3 acute and late toxicity, respectively. No Grade 5 acute toxicity was encountered. There were 2 fatal vascular ruptures during follow-up.

Conclusions

High-dose IMRT for recurrent and second primary head and neck cancer in previously irradiated territory leads to ≈20% long-term survival in a non-selected patient population. Identification of patients who would benefit most of curative IMRT is warranted.     

Reirradiation for recurrent head and neck cancer

Recurrence of head and neck cancer in a previously irradiated volume presents a challenging problem and has poor prognosis. A minority of patients are eligible for the preferred therapy, surgical resection. Systemic therapy is offered to patients with unresectable disease but offers little, if any, chance of cure. Repeat irradiation with systemic therapy is a potentially curative option. One randomized trial and several cooperative group and institutional studies support its use. Long-term disease-free survival has been observed, albeit with the risk of significant, possibly life threatening, late complications. Intensity-modulated radiotherapy has been shown to reduce toxicity and improve disease control. Novel systemic therapies and radiotherapy techniques, including stereotactic body radiotherapy, are under active study.