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27
Radiotherapy in Upper GI Tract Neoplasms
MS Anwar, Ju Ian Geh and David Spooner
Aims
This chapter aims to provide an evidence- based review of the role of radiotherapy in upper gastrointestinal malignancy. Multi- disciplinary team working is the key to optimal management of these patients. This involves close collaboration amongst surgeons, oncologists, gastroenterologists, radiologists, pathologists, palliative care physicians, specialist nurses and dieticians.
Each discipline should have an understand- ing of the clinical evidence that supports the use of the various treatment options available. Potential future developments in translational research and ongoing clinical trials are also discussed briefly.
Oesophagus
Oesophageal cancer is the third commonest gas- trointestinal malignancy and the tenth com- monest cancer in the world. Its incidence is 7.5 per 100 000 in the UK. In the Western world, there has been a significant increase in adeno- carcinoma of the lower oesophagus and gastro- oesophageal junction over the last 15 years. This is now more common than squamous carci- noma. At the time of diagnosis, the presence of locally advanced disease or distant metastases render approximately 60% of the patients sur- gically incurable. In a literature review of 122
papers of oesophageal cancer surgery, pub- lished between 1953 and 1978, the pooled 5-year survival of all 83 783 patients treated was 4%
(range 1% to 13%) [1]. Despite improvements in surgical technique and postoperative inten- sive care, the survival from oesophageal cancer remains poor. A further literature review of 46 692 patients treated between 1980 and 1988 showed a 5-year survival of 10% [2].
Radiotherapy
Preoperative (Neoadjuvant) Radiotherapy
Preoperative radiotherapy has been used in an attempt to improve resection rates and to decrease the risk of local recurrence. Five randomised trials have failed to demonstrate increased resectability or improved overall sur- vival. A subsequent meta-analysis of these trials using updated individual patient data also failed to show a statistically significant survival benefit from preoperative radiotherapy [3].
Radical Radiotherapy
Radical radiotherapy can result in long-term survival of patients who are not suitable for resection. In a literature review of 49 papers published between 1954 and 1979, the pooled 5-year survival of 8489 patients receiving radiotherapy was 6% (range 0% to 21%) [4].
Two small randomised trials of resectable
oesophageal cancer have compared radical radiotherapy with surgery and have showed a statistically significant survival advantage in favour of surgery [5,6]. A third trial by the Medical Research Council (MRC) failed to accrue.
Postoperative (Adjuvant) Radiotherapy
Radiotherapy has been used postoperatively to reduce the risk of local recurrence. In a University of Hong Kong trial, 130 patients were randomised to radiotherapy (49 Gy if curative resection or 52.5 Gy if palliative resection) or to no further treatment following oesophagec- tomy [7]. Although there was a lower risk of local recurrence in the palliative resection group receiving radiotherapy (20% vs 46%), patients receiving radiotherapy had a worse overall survival (median 8.7 months vs 15.2 months;
p = 0.02). This was due to treatment-related deaths from gastric ulceration and haemor- rhage, and was probably related to the large radiation doses given per fraction (3.5 Gy/frac- tion).
The second trial was carried out by the French University Association for Surgical Research [8]. A total of 221 patients with squamous car- cinoma were randomised to receive postopera- tive radiotherapy (45 to 55 Gy) or no further treatment following resection. Overall survival in both arms was identical (median 18 months).
Chemoradiotherapy (CRT)
The use of synchronous chemotherapy with radiotherapy, known as chemoradiotherapy (CRT), has been established in a number of gas- trointestinal tract cancers including oesophagus [9], pancreas [10], stomach [11], rectum and anus. In addition, there is convincing evidence that CRT improves survival in squamous carci- nomas of the uterine cervix and head and neck when compared with radiotherapy alone.
Preoperative (Neoadjuvant) Chemoradiotherapy
The intentions of delivering CRT prior to attempted surgical resection would include:
improving loco-regional disease control by increasing curative resection rates and reducing the risk of loco-regional recurrence
• reducing the risk of distant metastases
• improving the nutritional status of the patient by rapid relief of dysphagia which may optimise physical condition for surgery
• making the effectiveness of CRT assess- able by histological examination of the resected oesophagus.
In a review of preoperative CRT in oesophageal cancer [12], pooled data from 46 non-randomised studies totalling 2704 patients showed that the resection rate following CRT was 74%. Overall survival of the patients treated ranged from 8% to 55% at 3 years with a median range of 8 to 37 months. Of the patients under- going resection, 32% achieved pathological complete response (pCR), as defined by the reporting pathologist being unable to identify viable tumour cells within the specimen.
Pathological CR was associated with improved survival (29–92% at 3 years) and a low risk of loco-regional recurrence (3%).
There have been seven completed ran- domised trials comparing preoperative CRT fol- lowed by surgery with surgery alone [13–19]
(Table 27.1). Only one trial has demonstrated a statistically significant survival improvement from trimodality treatment [16]. In this trial, only patients with adenocarcinoma were included and the survival of the surgery-only arm was considered to be poor (6% at 3 years).
Although the EORTC trial [17] failed to show an improvement in overall survival, patients receiving preoperative CRT had superior disease-free survival. The higher postoperative mortality from trimodality treatment (12% vs 4%) had negated any survival benefit achieved.
The latest and second largest (256 patients) trial to report was conducted in Australasia (AGITG/TROG) [19]. Of the 105 patients who had resection following preoperative CRT, 15%
achieved pCR. This was more likely to occur in patients with squamous carcinoma (26%) than adenocarcinoma (9%). However, there was no difference in overall survival between the two groups (median of 21.7 months for preoperative CRT vs 18.5 months for surgery alone; p = 0.38).
The US Intergroup (NCCTG-C9781) trial closed due to a failure to accrue.
Any potential benefit from trimodality treat- ment has to be weighed against the risk of increased treatment-related morbidity and 27 · UPPER GASTROINTESTINAL SURGERY
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mortality. The pooled postoperative mortality of patients treated with preoperative CRT fol- lowed by surgery was 9%, but this ranged from 0% to 29% [12]. Although the risk of postoper- ative death was significantly higher for patients receiving CRT in the EORTC trial [17], the other randomised trials showed no increase in risk [14–19]. Adult respiratory distress syndrome, anastomotic leak and breakdown, pneumonia and sepsis were the commonest causes of post- operative death.
Definitive Chemoradiotherapy
A pilot study by the Toronto group of 35 patients with unresectable squamous carcinoma treated by CRT (45–50 Gy with mitomycin-C and fluorouracil (5FU) reported a 2-year sur- vival of 28% [20]. This appeared superior to a 2-year survival of 15% achieved in a similar cohort of patients who received radiotherapy alone.
In a review of the role of definitive CRT in oesophageal cancer (radiation doses from 40 to 70 Gy and synchronous 5FU and either mito- mycin-C or cisplatin) [21], the 2-year survival ranged from 28% to 72% in squamous carci- noma and 14% to 29% in adenocarcinoma.
Many of these patients had unresectable disease.
Several investigators have compared their results of definitive CRT with surgical controls (with or without CRT) and found no differences in survival.
The Radiation Therapy Oncology Group trial (RTOG 85–01) randomised 123 patients (88%
with squamous carcinoma) to CRT (50 Gy with two cycles of synchronous cisplatin and 5FU fol- lowed by two further cycles of adjuvant chemotherapy) or radiotherapy alone (64 Gy) [9]. At interim analysis, the median survival of patients receiving CRT was superior (14.1 months vs 9.3 months; p < 0.001). This led to early termination of the trial. Updated data of this trial as well as the results of a further cohort of 69 patients treated with the same CRT regimen were subsequently published [22]. The 3-year survival was 30% and 26% for patients receiving CRT in the randomised and non-ran- domised trial respectively versus 0% for radio- therapy alone.
The Eastern Cooperative Oncology Group (ECOG) randomised (EST-1282 trial) 119 patients with squamous carcinoma to receive
either CRT (radiotherapy with mitomycin-C and 5FU) or radiotherapy alone [23]. At 40 Gy, all patients were assessed for surgery or for definitive CRT (non-randomised). Forty-six patients (23 in CRT arm and 23 in radiotherapy arm) underwent resection. The median survival in the CRT arm was superior (14.8 months vs 9.2 months; p = 0.04). Despite the selection bias in favour of patients undergoing surgery, there was no difference in survival between resected and non-resected patients (Table 27.2).
Although the results of CRT appear to be superior to radiotherapy alone, the reported loco-regional failure rate as defined by persis- tent disease or subsequent recurrence following definitive CRT is 40% or more. In an attempt to improve loco-regional control, the next US Intergroup randomised trial (INT 0123) of CRT compared a higher radiation dose of 64.8 Gy with the standard dose of 50.4 Gy [26]. A total of 236 patients were entered (86% with squa- mous carcinoma). There was no difference in median (13.0 months vs 18.1 months) or 2-year (31% vs 40%) survival between high-dose and standard-dose treatment. However, there was an inexplicable excess of deaths during treat- ment in the high-dose arm (10% vs 2%), the majority of events occurring before the dose escalation was delivered.
Given the fact that survival following definitive CRT appeared equivalent to surgery alone, several investigators have questioned the routine role of surgery in resectable oesophageal cancer. To date, no randomised trial has compared CRT with surgery alone.
Murakami [27] reported a study of 40 patients with resectable squamous carcinoma who received induction CRT (44 Gy with cisplatin and 5FU). The patients (n = 30) who achieved a good initial response were selected to complete treatment with further CRT and the remaining proceeded to surgery. The overall 3-year sur- vival was 56% with no difference between the two groups. Comparable results were reported in another similar study of 32 patients (median disease-free survival of 16.1 months) [28].
A recently closed EORTC trial (FFCD 9102) randomised 259 patients (89% with squamous carcinoma) who had achieved a clinical response to induction CRT, to surgery or to further CRT [29]. The early results showed no difference in median survival (17.7 vs 19.3 months respectively) or 2-year survival (34% vs RADIOTHERAPY IN UPPER GI TRACT NEOPLASMS
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2 3 4 5 6 7 8 9 1011 1 2 3 4 5 6 7 8 9 2011 1 2 3 4 5 6 7 8 9 3011 1 2 3 4 5 6 7 8 9 4011 1 2 3 4 5 6 7 8 9 5011 1 2 311 Table 27.1.Randomised trials of preoperative chemoradiotherapy and surgery vs surgery alone in resectable oesophageal carcinoma TrialRandomisationNo.HistologyRadio-Chemo-ResectionPostoperativePCRMedian2-year3-year SCCAdenotherapytherapyRate (%)Mortality(%)SurvivalSurvivalSurvival (months)(%)(%) Nygaard et alCRT+S4747035 GyCis, Bleo6624NS72317 [13]Chemo+S50500NilCis, Bleo5815NS663 RT+S4848035 GyNil5411NS102521 S only41410NilNil6813–6139 p=0.3 Le Prise et alCRT+S4141020 GyCis, 5FU85810102719 [14]S only45450NilNil847–113314 p=0.6 Apinop et alCRT+S3535040 GyCis, 5FU7412209.73026 [15]S only34340NilNil10015–7.42320 p=0.4 Walsh et alCRT+S5805840 GyCis, 5FU901022163732 [16]S only55055NilNil1004–11266 p=0.01 Bosset et alCRT+S143143037 GyCis78122018.64836 [17]S only1391390NilNil684–18.64234 p=0.8 Urba et al [18]CRT+S50133745 GyCis, 5FU,9022816.94030 Vinblast S only501238NilNil900–17.63416 p0.15 Burmeister et alCRT+S12892*15735 GyCis, 5FUNS3.115.221.7NSNS [19]S only128NilNilNS4.6–18.5NSNS SCC, squamous cell carcinoma; Adeno, adenocarcinoma; PCR, pathological complete response; CRT, chemoradiotherapy; S, surgery; Chemo, chemotherapy; RT, radiotherapy; Cis, Cisplatin; Bleb, bleomycin, NS, not stated; 5FU, fluorouracil; Vinblast, vinblastin; * mixed/undifferentiated.
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311 Tabl
e 27.2.Recent randomised trials of definitive chemoradiotherapy versus radiotherapy in unresectable oesophageal carcinoma TrialRandomisationNo. of patientsRadiotherapyChemotherapyMedian survival2-year3-year5-year totalSCCAdeno(months)survival (%)survival (%)survival (%) Araujo et al [24]CRT2828050 GyBleo, Mito, Cis15382216 RT31310sameNil1522126 p=0.16 Roussel et al [25]CRT110110040 GyCis7.820NS8 (4-year) RT1111110sameNil10.516NS10 (4-year) p=0.17 Smith et al [23]CRT5959040–60 GyMito, 5FU14.8NS279 RT60600sameNil9.2NS127 p=0.04 Herskovic [9], CRT6152950 Gy5FU, Cis14.1363026 Al-Sarraf [22]RT6256664 GyNil9.31000 Cooper et alCRT (Non-R)69551450 Gy5FU, Cis17.2352614 p=0.0001 SCC, squamous cell carcinoma; Adeno, Adenocarcinoma; CRT, chemoradiotherapy; RT, radiotherapy; Bleo, bleomycin; Mito, mitomycin; Cis, cisplatin; NS, Not stated; 5FU, 5fluorouracil; Non-R; non-randomised.
40%). However, there were more deaths within 3 months of commencing CRT in the surgery arm (9% vs 1%; p = 0.002). Therefore, there is good evidence to support the use of definitive CRT in resectable squamous carcinoma of the oesophagus as an alternative to surgery [23, 27–29].
The majority of available data on CRT in oesophageal cancer used synchronous 5FU with either cisplatin or mitomycin-C. Since then, many more chemotherapy drugs have been incorporated into routine use for cancer therapy. The assessment of these as potentially useful radiosensitisers has produced interesting results. Paclitaxel appears safe in oesophageal cancer and high pCR rates can be achieved with CRT given preoperatively. Other promising agents include irinotecan and oxaliplatin.
Radiotherapy Technique
Precise identification of the site and local extent of the primary tumour and the involved lymph nodes is essential. The gross tumour volume (GTV) can be defined by a combination of cross-sectional imaging (CT and/or MRI), endoscopic ultrasound and barium swallow.
Radiotherapy planning is usually performed by CT localisation of the tumour and oesophagus.
The clinical target volume (CTV) is the volume defined to encompass the GTV, the likely micro- scopic extension beyond the GTV and the immediate draining lymph nodes. The planning target volume (PTV) includes a final margin which is added to compensate for daily varia- tions in patient positioning and organ move- ment with respiration (Figures 27.1 and 27.2).
The treatment is planned to encompass the entire PTV. At the same time, the dose received by the surrounding organs such as the spinal cord, lungs and heart will need to be limited to within their normal tissue tolerance. The use of conformal and intensity modulated radiother- apy (IMRT) should enable improved sparing of normal organs, by better conformation of the high dose volume around the tumour. These techniques require three-dimensional computer planning and linear accelerators fitted with mul- tileaf collimators (MLC). These may allow radi- ation dose escalation to the tumour without unacceptable toxicity to the surrounding organs. There may also be a future role for non- conventional radiotherapy scheduling such as
acceleration (over a shorter treatment duration) or hyperfractionation (treatment more than once a day).
Toxicity of Radiotherapy and Chemoradiotherapy
Acute side effects of radiotherapy include radiation-induced mucositis of the oesophagus.
This can become secondarily infected by candida and will require antifungal therapy.
Symptoms of odynophagia, altered taste and anorexia are common and usually commence 10 to 14 days after starting radiotherapy.
Maintenance of nutritional status is essential to support patients through their treatment.
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1111 2 3 4 5 6 7 8 9 1011 1 2 3 4 5 6 7 8 9 2011 1 2 3 4 5 6 7 8 9 3011 1 2 3 4 5 6 7 8 9 4011 1 2 3 4 5 6 7 8 9 5011 1 2 311 Figure 27.1. A simulator film during barium swallow to delineate the target volume for radiotherapy in cancer of the oesophagus.
Figure 27.2. CT planning for cancer of the oesophagus.
Computer-generated isodose distribution of the radiation beams is also shown on this CT slice.
Nasogastric or parenteral feeding may need to be commenced if significant weight loss con- tinues after commencement of radiotherapy.
Patients are encouraged to cease smoking and alcohol during radiotherapy as these may exac- erbate acute and long-term toxicity. Radiation- induced tracheitis can cause a persistent cough associated with thick mucus production. Acute pneumonitis can occur within the first 3 months and may cause a dry cough, dyspnoea and low grade pyrexia. Acute radiation mediastinitis is a rare complication causing chest pain, pyrexia and dyspnoea. In severe cases, hospital admis- sion is necessary to exclude an oesophageal perforation.
The commonest long-term toxicity of radio- therapy is oesophageal stricture formation. The most likely contributing cause is the extensive tumour destruction and subsequent treatment- related fibrosis. A tracheo-oesophageal fistula can occasionally develop but again, this is more commonly due to direct tumour invasion.
Radiotherapy is as safe and effective in suffi- ciently fit elderly patients as it is in a younger population.
Palliative Treatment
For patients deemed incurable, short courses of palliative radiotherapy may be effective in improving symptoms of dysphagia and/or pain.
Radiation doses of 20 Gy in 5 fractions or 30 Gy in 10 fractions are usually tolerated well and are associated with a low risk of serious toxicity.
This can be given in combination with other interventions including oesophageal dilation, laser ablation and stenting. In addition, chemotherapy may be useful in delaying further disease progression and in prolonging survival.
This is discussed in Chapter 26.
The insertion of radioactive sources (usually iridium-192) into the oesophagus, known as brachytherapy, can be an effective means of delivering high doses of radiation to the intra- luminal component of the tumour with rela- tively low doses to surrounding structures.
Using a high dose rate (HDR) selectron machine, 16 Gy in two fractions or 18 Gy in three fractions given weekly have been shown to offer excellent palliation. Brachytherapy in combina- tion with laser ablation may reduce the fre- quency of required endoscopic dilatations in selected patients.
The selection of the treatment modality used to palliate a particular patient should take into account the site of disease, related symptoms, general physical condition and social circum- stances. An additional factor is the level of expertise and technology available locally for each of these interventions.
Other Histological Types
Small cell carcinoma is occasionally seen in the oesophagus. Its clinical behaviour of early sys- temic spread is similar to small cell carcinoma of the lung. Multidrug combination chemother- apy with or without radiotherapy is probably the optimum treatment. Surgery may be con- sidered for selected patients. The role of CRT is yet to be defined.
Carcinoma of the oesophagus with adenoid cystic differentiation has been reported to be clinically and morphologically distinct from adenoid cystic carcinoma arising from salivary glands. Surgical resection is the mainstay of treatment.
Primary oesophageal T-cell non-Hodgkin’s lymphoma is rare. Most cases present with evi- dence of widespread disease and chemotherapy would be the appropriate treatment. When truly localised, radiotherapy alone can be successful.
Summary and Future
Although surgery remains the standard against which new treatments must be compared, there is emerging evidence that stage for stage, the survival from CRT alone is equivalent to surgery alone [30]. Salvage oesophagectomy following CRT failure is feasible in some cases and the results are encouraging [27]. Although com- monly given, the role of preoperative CRT remains unproven and therefore can only be recommended in the context of a clinical trial.
There is no proven role for postoperative radio- therapy.
It is clear that different treatment modalities are appropriate for different patients, but the means of selecting the appropriate treatment for the individual patient is lacking. The standard of care for surgery has also progressed. Two cycles of preoperative cisplatin and 5FU chemotherapy (without radiation) have been shown to increase curative resection rates (60%
vs 54%) and overall survival at 2 years (43% vs RADIOTHERAPY IN UPPER GI TRACT NEOPLASMS
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34%) in an MRC randomised trial of 802 patients [31]. In the future, the management of adenocarcinoma and squamous carcinoma is likely to diverge. Patients who achieve pCR fol- lowing CRT for squamous carcinoma are unlikely to benefit from resection, but at the present time there is no reliable test to predict for this. Further research is needed to develop these tests. However, a non-surgical approach will enable organ preservation [30] and may lead to lower treatment-related mortality [28]
and improved quality of life [32]. This can only be justified if there is no survival penalty.
Improving pretreatment loco-regional staging by the routine use of endoscopic ultra- sound and multislice CT scanning in regional gastro-oesophageal cancer units should be the standard. The use of 18-fluorodeoyxglucose (FDG) positron emission tomography (PET) to detect distant metastases not identified by CT scan will help spare approximately 20% of patients from a non-curative resection or an
“open and shut” procedure. Serial FDG-PET scanning may also be useful in detecting early response to radiotherapy.
In order to improve loco-regional control of this cancer, the optimum combination of chemotherapy and radiotherapy needs to be defined by refining existing regimens, assessing new agents and improving radiation dose delivery. Prevention of systemic recurrence remains an elusive target but new chemotherapy drugs and combinations are being explored for the future. In the next decade, there will be an expansion of research into the molecular biol- ogy of malignant tumours and their response to chemotherapy and radiotherapy. The develop- ment of in vitro predictive testing may help to tailor treatment strategies to achieve the best responses. Cyclin D1 immunoreactivity and metallothionein expression both appear to cor- relate with sensitivity to CRT in oesophageal cancer.
Stomach
Although there has been a decrease in the inci- dence of gastric adenocarcinoma involving the body and pylorus in the Western world, that of cardia and gastro-oesophageal junction tumours has increased markedly. The overall 5- year survival of all patients with gastric carci-
noma remains poor (between 5% and 15%).
Although the mainstay of treatment remains surgical resection, the ultimate risk of recur- rence is high. Adjuvant treatments are an attempt to improve outcome.
Radiotherapy
Radiotherapy to the stomach is limited by the mobility and variation in size of this organ. In addition, the radiation dose that can be safely delivered is also limited by the presence of sur- rounding radiosensitive organs including the small bowel, liver, kidneys and spinal cord (Figure 27.3).
In a Chinese trial, 370 patients with adeno- carcinoma of the gastric cardia were ran- domised to receive radiotherapy (40 Gy) prior to surgery or surgery alone [33]. Patients in the radiotherapy arm had higher resection rates (89% vs 79%; p < 0.01) and an improved 5-year survival (30.1% vs 19.7%; p = 0.009).
The British Stomach Cancer Group Trial ran- domised 436 patients who had undergone resec- tion for adenocarcinoma of the stomach to receive postoperative radiotherapy (45–50 Gy), chemotherapy (mitomycin-C, doxorubicin and 5FU) or no further treatment [34]. There was no difference in survival between the three arms (median 12.9 months vs 17.3 months vs 14.7 months; 5 years 12% vs 19% vs 20%; p = 0.14).
27 · UPPER GASTROINTESTINAL SURGERY
1111 2 3 4 5 6 7 8 9 1011 1 2 3 4 5 6 7 8 9 2011 1 2 3 4 5 6 7 8 9 3011 1 2 3 4 5 6 7 8 9 4011 1 2 3 4 5 6 7 8 9 5011 1 2 311 Figure 27.3. A schematic diagram of the cross-section of the abdomen at the level of the L1 vertebral body showing stomach and other anatomic organs in its vicinity that may be at risk of radiation damage during radiotherapy to the stomach. 1, spleen;
2, small bowel; 3, stomach; 4, transverse colon; 5, descending colon; 6, left kidney; 7, pancreas; 8, left lobe of liver; 9, abdominal aorta; 10, L1 vertebral body; 11, spinal cord/cauda equina; 12, spinal process of L1; 13, inferior vena cava; 14, right lobe of liver;
15, right kidney.
Chemoradiotherapy
The role of postoperative combined chemother- apy and radiotherapy has been assessed by the US Intergroup in a randomised trial (INT 0116) which compared CRT with no further treatment in 556 patients who had undergone curative resection for locally advanced adenocarcinoma of the stomach and gastro-oesophageal junction [11]. In the treatment arm, the patients received one cycle of 5FU and folinic acid, followed by CRT (45 Gy with synchronous 5FU and folinic acid), followed by a further cycle of 5FU and folinic acid. Most patients had tumours involv- ing the distal stomach and 85% had lymph node involvement on histological examination of the resection specimen. Of note, 54% of the patients had undergone a D0 dissection, meaning a less than complete dissection of the N1 lymph nodes. The median survival was 36 months for the CRT arm compared with 27 months for the surgery alone arm (p = 0.005), with a 3-year sur- vival of 50% versus 41% respectively.
The Gastric Surgical Adjuvant Radiotherapy Consensus Report [35] has outlined the factors to be considered for planning postoperative CRT. These include anatomy, pathways of tumour spread, patterns of failure and surgical techniques. Nevertheless, the implementation of such complex and resource consuming indi- vidual planning can be justified by improved results in selected patients who are motivated and are of sufficiently good physical condition.
Mucosa Associated Lymphoid Tissue (MALT) Lymphoma
The stomach is the commonest site of gastroin- testinal non-Hodgkin’s lymphoma. The com- monest subtype is the MALT lymphoma. This is commonly associated with Helicobacter pylori infection. Antibiotic therapy has resulted in complete remissions in many patients with early disease [36]. A combination of chemotherapy and involved field radiotherapy in the manage- ment of Ann Arbor stage I and II MALT lym- phomas is associated with good response rates and survival.
Small Bowel
Although a wide variety of benign and malig- nant neoplasms can arise from the small intes-
tine, the numbers are exceedingly small and the role of radiotherapy negligible. Primary malig- nant tumours range from adenocarcinoma through varieties of sarcomas and lymphomas to carcinoid tumour. Radiotherapy is unlikely to be useful not only because small bowel is diffi- cult to target due to its mobile nature but also because of its radiosensitivity. Palliative radio- therapy may be considered to control acute or chronic haemorrhage.
Questions
1. Outline the arguments for either surgery or radiotherapy for squamous carci- noma of the oesophagus.
2. Criticise the trial suggesting possible benefit of chemoradiotherapy for cancer of the stomach.
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