Adaptive radiotherapy for head and neck cancers: Fact or fallacy to improve therapeutic ratio?

Modern standards of precision radiotherapy, primarily driven by the technological advances of intensity modulation and image guidance, have led to increased versatility in radiotherapy planning and delivery. The ability to shape doses around critical normal organs, while simultaneously "painting" boost doses to the tumor have translated to substantial therapeutic gains in head and neck cancer patients. Recently, dose adaptation (or adaptive radiotherapy) has been proposed as a novel concept to enhance the therapeutic ratio of head and neck radiotherapy, facilitated in part by the onset of molecular and functional imaging. These contemporary imaging techniques have enabled visualisation of the spatial molecular architecture of the tumor. Daily cone-beam imaging, besides improving treatment accuracy, offers another unique angle to explore radiomics - a novel high throughput feature extraction and selection workflow, for adapting radiotherapy based on real-time tumor changes. Here, we review the existing evidence of molecular and functional imaging in head and neck cancers, as well as the current application of adaptive radiotherapy in the treatment of this tumor type. We propose that adaptive radiotherapy can be further exploited through a systematic application of molecular and functional imaging, including radiomics, at the different phases of planning and treatment.

Gemcitabine in metastatic nasopharyngeal carcinoma of the undifferentiated type.

BACKGROUND: We conducted two parallel phase II trials in chemonaïve and previously treated patients with metastatic nasopharyngeal carcinoma (NPC) to evaluate the tumour response, progression-free and overall survival, and toxicity of gemcitabine. PATIENTS AND METHODS: Gemcitabine 1250 mg/m2 was given on days 1 and 8 of a 21-day cycle. Patients with an Eastern Cooperative Oncology Group performance status <2, adequate renal, hepatic and bone marrow function, and radiologically measurable NPC were eligible. RESULTS: Twenty-five chemonaïve and 27 previously treated patients were enrolled. The overall response rate was 28% [95% confidence interval (CI) 14% to 48%] for the chemonaïve and 48% (95% CI 31% to 66%) for previously treated patients. Toxicities greater than or equal to grade 3 occurred in 15 (60%) chemonaïve and 13 (48%) previously treated patients. Neutropenia was uncommon in chemonaïve patients, but occurred in 37% of previously treated patients. The median time to progression was 3.6 months (range 0.9-7.9) for chemonaïve and 5.1 months (0.9-13.1) for previously treated patients. Median overall survival time was 7.2 months (1.4-15.6) and 10.5 months (2.4-15.0) for chemonaïve and previously treated patients, respectively. CONCLUSIONS: Gemcitabine has moderate activity in NPC with minimal toxicity, and is also an effective salvage agent for patients who have failed or progressed after treatment with other agents.

Nasopharyngeal carcinoma: review of how imaging affects staging.

Imaging plays an important role in the staging of carcinoma of the nasopharynx. Accurate staging is necessary as the treatment is directly dependent on stage. Clinical examination provides information on mucosal involvement but is unable to determine the deep extension or presence of skull base invasion or intracranial spread. The 1997 International Union Against Cancer (UICC) and American Joint Committee on Cancer (AJCC) staging manuals were a collaborative project that provided a unified classification for nasopharyngeal carcinoma (NPC). The majority of staging can be identified only on imaging and not by clinical examination. The intent of this article is to provide information on the specific imaging findings that will directly affect the stage and treatment of NPC.

Occupational burns in the Burns Centre at the Singapore General Hospital.

This study reviewed all work-related burn injuries within the period 1 April 1992 to 31 March 1993 for the purpose of establishing data on occupational burns in Singapore to identify the specific at-risk population and formulate prevention strategies. All 163 patients who were admitted to the Burns Centre, Singapore General Hospital, as a result of burns suffered in the workplace were reviewed using the World Health Organisation Burns Data Protocol. Burns data recorded included demography, industrial sector involved, aetiology, extent of injury and eventual outcome in terms of mortality and morbidity. Occupational burns accounted for 45% of all admissions to the Burns Centre. Male workers in the 20 to 40-year age group predominated with 90% of admissions. The most common aetiology was flame burns and explosions (52.8%) followed by scalds (24.5%) and electrical (10.4%), chemical (6.1%) and contact (6.1%) burns. The average body surface area (BSA) involved was 8% (range 0.25% to 90%). Twenty-seven patients suffered full-thickness burns and the average area of involvement was 2% (range 0.25% to 90%). The most common anatomical regions involved were the upper limbs (46.3%) followed by lower limbs (31.9%). Eighteen patients (11.0%) sustained major burns requiring fluid resuscitation and 39 patients (23.9%) sustained respiratory burns. Seven patients died, giving a mortality rate of 4.3%. The average BSA for these patients was 46.4% and all had respiratory burns. In all, occupational burns accounted for 2011 patient-days of hospitalization, 630,637 lost days at work and inpatient treatment costs amounting to S $1.32 million.(ABSTRACT TRUNCATED AT 250 WORDS)

HDR intraluminal brachytherapy for lung tumours--a case report.

The lung is a common site for cancer to occur, for both primary as well as metastases. The presence of such tumours can give rise to symptoms such as haemoptysis, cough, breathlessness and pneumonia. In most cases, treatment is strictly for palliation. We present a case report of a patient with an endobronchial metastasis from a primary hypernephroma which recurred following external beam radiotherapy. He was treated with a single fraction of intraluminal brachytherapy to a dose of 10Gy at 1 cm from the axis on a High Dose Rate Ir192 Remote Afterloading Machine. There were no adverse effects following treatment. On follow-up 7 months later, the patient did not have any further recurrence of breathlessness although his disease had progressed at other sites.

Intraluminal brachytherapy in the treatment of oesophageal cancers--some preliminary results.

Cancer of the oesophagus is the sixth commonest cancer in males in Singapore. The majority occur in the elderly and patients are often debilitated at presentation. Treatment is often aimed at palliation only. In this article, the preliminary results of 15 patients treated solely on a high dose rate remote afterloading Gammamed brachytherapy machine with an Iridium 192 (Ir192) source are reported. The patients were given 15 Gray (Gy) in a single or two 7.5 Gray fractions. All the patients treated had some improvement of their dysphagia, and seven out of 11 (63%) evaluable patients had symptom improvement lasting at least 11 weeks.

Objective assessment of research performance.

Research output in academic institutions need critical and objective assessment. Publications are an important avenue by which research by an academic can be evaluated. Journals in which such publications appear may be ranked and weight age given to publications in highly ranked journals. The number of citations of an academic's work by peers is another assessment of quality of research output. Firstly subjective peer assessment although flawed by interpersonal bias has its merits especially when evaluation is by an outsider of the institution.

The dropped big toe.

Surgical procedures for exposure of the upper third of the fibula have been known to cause weakness of the long extensor of the big toe post-operatively. The authors present three representative cases of surgically induced dropped big toe. From cadaveric dissection, an anatomic basis was found for this phenomenon. The tibialis anterior and extensor digitorum longus muscles have their origin at the proximal end of the leg and receive their first motor innervation from a branch that arises from the common peroneal or deep peroneal nerve at about the level of the neck of the fibula. However, the extensor hallucis longus muscle originates in the middle one-third of the leg and the nerves innervating this muscle run a long course in close proximity to the fibula for up to ten centimeters from a level below the neck of the fibula before entering the muscle. Surgical intervention in the proximal one-third of the fibula just distal to the origin of the first motor branch to the tibialis anterior and extensor digitorum longus muscles carries a risk of injury to the nerves innervating the extensor hallucis longus.

Glutaraldehyde-tanned microvascular grafts.

In this study the efficacy of preserving microvascular heterografts with glutaraldehyde tanning was investigated. These were compared with glutaraldehyde-tanned autografts. Previous studies have found that untreated autograft veins maintain a 95% patency rate, whilst untreated heterograft veins (Group 1) had a 15% patency rate at 4 weeks in this study. Autogenous glutaraldehyde-tanned rabbit carotid arterial grafts (Group 2) and glutaraldehyde-tanned human chorionic veins (Group 3) were interposed in rabbit femoral or carotid arteries. Fifty per cent and 75% patency rates were achieved respectively at 4 weeks. The low patency rate of the autogenous group suggests that the glutaraldehyde tanning technique itself is largely responsible for the low patency of glutaraldehyde-tanned human chorionic veins rather than any immunological response. Therefore if human chorionic veins are to be used as a readily available preserved microvascular graft, further investigation is required to develop another technique which will reduce antigenicity without promoting thrombosis.

A new technique of vaginal reconstruction using neurovascular pudendal-thigh flaps: a preliminary report.

The blood supply to the skin of the perineum, medial groin, and upper thigh was studied in fresh female cadavers. The pudendal-thigh flap was designed as a result to reconstruct the vagina. The flaps are raised bilaterally in the groin crease just lateral to the labia majora and then are transposed toward the midline and sutured together to form a skin-lined cul-de-sac which opens at the introitus. The technique has been used successfully in three patients to reconstruct the vagina. The first patient, an adult, was reconstructed after total pelvic exenteration for malignancy, while two children had reconstructions for congenital vaginal anomalies. This technique is superior to currently available methods because it is simple and reliable. No stents or dilators are needed. It is safe technique without complications in our hands. The reconstructed vagina has a natural angle for intercourse and is sensate. The donor scars in the groin are well hidden.

Reversed venous flow in the distally pedicled radial forearm flap: surgical implications.

In recent years the distally pedicled radial forearm flap has proved to be a versatile technique for resurfacing the hand. The venous drainage of this flap, however, has remained a puzzle. Various explanations have been suggested, including bypass of the valves by collateral veins and by crossover between the venae comitantes. However, venous drainage must be against the direction of the valves in at least one segment of the veins. The question of reversed venous flow and how it may be achieved reliably is addressed in this study. Timmons has postulated three criteria which all must be satisfied for reversal of venous flow. These criteria, namely higher proximal venous pressure, denervation of the valves, and the filling of the venous segments may be achieved satisfactorily if a few precautions are taken and certain technical manoeuvres performed. The criteria were re-examined in the light of known physiological phenomena. In addition, certain pertinent anatomical facts which arose from our cadaveric studies and which may be exploited to advantage are discussed. Our studies have led to greater understanding of reversed venous flow and to greater success with this flap in our clinical practice.

Simultaneous dislocations of the interphalangeal and carpometacarpal joints of the thumb: a case report.

A case of simultaneous dislocations of the interphalangeal and carpometacarpal joints of the thumb after a fall is described. We believe this is a unique situation not reported before in the literature. The results of operative intervention of the open IP joint and closed CMC joint dislocations resulted in a stable pain-free thumb with a good range of motion.

Reconstruction of the lower leg and foot with the reverse-pedicled anterior tibial flap: preliminary report of a new fasciocutaneous flap.

The blood supply to the skin of the anterior leg was studied in 10 fresh cadavers. Particular attention was paid to the intermuscular septal blood vessels, which emerge in the cleft between tibialis anterior and extensor hallucis longus and extensor digitorum longus muscles. With this anatomical knowledge, the reverse-pedicled anterior tibial fasciocutaneous flap was designed and transferred clinically to cover lower leg and foot defects in 6 patients. Three case reports are detailed. The factors which allow a distally based flap to be raised in the lower leg against the direction of venous valves are also described. The versatility of this new flap in the reconstruction of defects of the lower leg and foot is discussed.

Reconstruction of an orthotopic functional anus after abdominoperineal resection.

A case is reported of the reconstruction of a continent anus after an abdominoperineal resection for a patient who presented with a Dukes B adenocarcinoma at 4.5 cm from the anal verge. After a radical excision, the perineal colostomy was sited orthotopically. The right gracilis muscle, completely detached from the thigh except for the neurovascular pedicle, was wrapped around the neorectum at the original level of the levator ani, in an alpha loop configuration. The free ends of the alpha loop pointing anteriorly were sutured to the public bone. Thus the 80 degrees ano-rectal angle was reconstructed. A temporary transverse colostomy was also performed. After closure of the colostomy at eight weeks, the patient was immediately continent of soft stools without a learning period. Pressure studies of the new sphincter are also reported.