Treatment Of Limited Stage Sclc Nursing Essay

Lung cancer is the most common malignancy in the world; more than1.3 million new cases are diagnosed every year (Cancer Research UK 2013). In the UK lung cancer claimed nearly 35,000 lives last year making it the deadliest cancer for both men and women. (Cancer Research UK 2013) Tobacco smoking is the most important cause of lung cancers with 80%–90% arising in cigarette Smokers. A lifetime smoker has a 20-to 30-fold increased risk of developing lung cancer compared to a lifetime non-smoker. Other risk factors include; being exposed to arsenic, asbestos, radioactive dust, or radon. (Minna, Roth and Gazdar 2002)

There are four main histological types that encompass the majority of lung cancers. These include Small Cell Lung Cancers (SCLC), and the three Non- Small Cell Lung cancers (NSCLC) Squamous Cell carcinoma, Adrenocarcinoma and large cell carcinoma. Squamous Cell Carcinoma and SCLC arise mainly from the central airways, while adenocarcinomas (including bronchioloalveolar cancer) are peripherally located (Tobias and Hochhauser 2010). Large cell carcinomas can occur in any part of the lung. They tend to grow and spread faster than the other types of NSCLC. (Minna, Roth and Gazdar 2002). NSCLC are grouped together because they behave in a similar way and respond to treatment in a different way to SCLC.

Small Cell lung cancer (SCLC) accounts for 20-25% of lung cancer worldwide. It is an aggressive form of lung cancer that has a high metastatic potential. In fact it is the most aggressive of all the lung cancer cell types, with a median survival time without treatment of 2–4 months. However the incidence has been in decline in recent years due to changes in smoking habits. (Cooper and Spiro 2006)

The TNM staging system has little use in SCLC except for a few patients who will benefit from detailed staging as their disease may have a chance to be surgically removed. This is rare and only occurs in about 5% of cases. (Cooper and Spiro 2006) A much simpler two stage system has been devised based on the patient’s suitability for radical radiotherapy. Patients with disease confined to one hemithorax, with or without mediastinal, contralateral hilar, or ipsilateral supraclavicular or scalene lymph nodes were considered to have limited-stage disease, whereas those with disease involvement at any other location were considered to have extensive-stage disease. Generally approximately 30% of patients have limited disease stage. Under the NICE guidelines limited stage disease broadly corresponding to T1–4, N0–3, M0, while extensive corresponds to T1–4, N0–3, M1a/b and early-stage SCLC T1–2a, N0, M0. (NHS 2011)

Treatment of Limited Stage SCLC

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Chemo-radiation therapy is recommended as standard management for limited-stage SCLC (NHS 2011). In the researchers department patients receive 4 cycles of Cisplatin and Eoposide. Radiotherapy is then administered concurrently 45Gy in 25 fractions, five days per week over 33-35 days. Prophylactic cranial irradiation (PCI) will be delivered subsequently if a complete response has been attained with this induction Chemo-radiation therapy (Department Protocol 2013). This corresponds to the NICE guidelines, however they do highlight that sequential rather and concurrent radical radiotherapy should be given to patients who have a WHO performance status of >2. (NHS 2011)

The CONVERT phase III trial is currently running in both Europe and Canada. The trial is a 2-arm randomised controlled trial of concurrent chemo-radiotherapy comparing twice-daily and once-daily radiotherapy with patients who have limited stage SCLC and a good performance status (Faivre-Finn and Falk 2012). Several sites in the UK are currently running the study which closes in May 2013. Results are to be released later in the year and it’s hoped that hyperfractionated radiotherapy may offer some advantage. Nevertheless it should continue to be confined to the trial setting until a benefit has been confirmed. See figure 1 for explanation of control arms.

Patents whose small-cell lung cancer has been successfully treated nonetheless have a 50–67% risk of developing metastases in the central nervous system. (Cooper and Spiro 2006) Therefore, in patients who have had a complete response to chemotherapy, cranial irradiation is used prophylactically. The optimal fractionation of PCI in LS-SCLC appears to be 25 Gy in 10 fractions, as this was associated with improved OS compared with alternative PCI schedules. (Cooper and Spiro 2006)

Surgery followed by chemotherapy is recommended for stage T1-2N0 disease (NHS 2011). In the researchers clinical placement site patients with limited-stage disease T1-T2 N0 M0, are offered surgery to remove the primary tumour. These patients also receive post-operative systemic chemotherapy (Department Protocol 2013). The role of thoracic and prophylactic cranial irradiation (PCI) is not clear when patients present with early disease that can be surgically removed. A recent study by (Gong et al. 2013) Looked at the efficacy of PCI for patients who have undergone surgical resection. They observed that early stage SCLC patients without PCI had a favourable 5-year survival rate of 54.8%. Therefore, patients with early stage SCLC who have had a complete resection may not need PCI. However another study by (Bischof et al. 2007)Reviewed 39 patients with early stage SCLC who were treated with complete surgical resection. It was reported that 4 of the 18 patients (22%) in the group without PCI experienced brain metastases, compared with 100% brain metastasis-free survival after PCI. However, no statistics about brain metastasis rate in stage I disease alone were given, rendering their results statistically insignificant

Treatment of SCLC Extensive disease

Blood –borne spread in SCLC is more frequent and typically occurs earlier than other lung cancers. The skeleton is often a site of metastases especially vertebrae, ribs and pelvis. Widespread infiltration into bone marrow occurs. Other common sites are the liver CNS and adrenals. (Tobias and Hochhauser 2010)

To help tackle the metastatic disease the researchers department uses combination chemotherapy containing platinum. Radiotherapy is only used for symptomatic bone metastases, cord compression; or when the patient is too ill to withstand chemotherapy this corresponds to what is advised in the NICE guidelines (Department Protocol 2013). However A recent study (Yee et al. 2012) looked at the addition of local thoracic RT for ES-SCLC In an attempt to minimise any intrathoracic disease recurrences. Thoracic RT was given 4-8 weeks after the last cycle of chemotherapy with a prescribed dose of 40gy in 15fractions, in which 32 patients took part. Symptomatic chest recurrences only appeared in 5/32 patients. Although the findings from this research seem positive, the sample size and lack of statistical analysis highlight the need for ongoing randomized trial of post-chemotherapy chest RT for ES-SCLC.

PCI for ES-SCLC is something that is not routinely practiced at the researcher’s clinical department. A study by (Slotman et al. 2007) reported that PCI significantly reduced the risk of symptomatic brain metastases and significantly prolonged progression-free

Survival time (p = 0.0218). Slotman suggested that PCI should be offered to all patients with ES-SCLC who respond to chemotherapy. However various doses were used ranging from 20gy/5# to 30gy/12#, with not clear indication of an optimal dose. Nevertheless his findings yielded promising results and PCI for ES-SCLC is now advised in the NICE guidelines.

Despite the high sensitivity to chemotherapy, nearly all patients will suffer from the development of chemotherapy resistance and will eventually die from their condition. It is at this point multidisciplinary support and palliative care teams have an essential role in making life as comfortable as possible for the patient (Minna, Roth and Gazdar 2002).

(Harding and Murtagh 2006) Suggest that a proactive approach of palliative medicine/care is vital to reduce distressing symptoms that are apparent in terminal lung cancer and embraces surgical, medical, and psychological intervention. The NICE guidelines state "Patients who may benefit from specialist palliative care services should be identified and referred without delay" (NHS 2011). This is backed up in the UK’s National Cancer Plan as one of its main objectives is to improve the experience of cancer patients by integrating palliative care services both general and specialist. These skills expand beyond pain and symptom control into communication skills, family care, and the use of terminal care protocols to implement evidence-based end-of-life care pathway

NSCLC

NSCLC is the most common type of lung cancer accounting for around 80% of diagnosed cases. (Walker 2008). NSCLC is staged using the TNM staging system please refer to Figure 2 in the appendix of a full explanation of the system.

Surgery is a treatment possibility in around 30% of cases. (Tobias and Hochhauser 2010). Patients should be considered suitable for surgery if they are fit enough for operation and have a non-small cell tumour of stage I or II (NHS 2011). For the majority of cases chemotherapy and radiotherapy either combined or alone is the main treatment modality for NSCLC (Walker 2008). The NICE guidelines state radical radiotherapy should be given to patients with stage I, II or III NSCLC who have a good performance status. In the researchers department radical radiotherapy is delivered by 3D conformal radiotherapy (3D-CRT) and guided by dose volume histograms for both tumour volume and normal tissue tolerances. The percentage of normal lung receiving more than 20 Gy should not exceed 35% (V20 < 35%) (Department Protocol 2013).

Sometimes NSCLC can be treated using two phases of radiotherapy. In the researchers department The first phase uses simple parallel opposed pair (30gy10#), mainly to cover any mediastinum lymph tissue, the second phase uses 3D-CRT to target the precise tumour volume and minimising toxicity to healthy tissue (Department Protocol 2013).

A recent treatment advance is intensity-modulated radiation therapy (IMRT). This therapy allows delivery of a high dose of radiation to lung tumours while decreasing the radiation to the organs at risk, (heart/lung/spinal cord (Haas 2008). It is hard not to irradiate the spinal cord even with sophisticated 3D-Comfromal planned techniques used in the researchers department, IMRT can be used to minimise this. A study by (Grills et al. 2003) Compared IMRT with 3D conformal radiation therapy. Grills et al reported that IMRT reduced doses to organs at risk by 15−40% and increased target doses by 25−30% compared to 3D conformal radiotherapy. In addition IMRT was shown to add significant value in node positive cases and in tumours close to the oesophagus. This suggests IMRT could be a valuable treatment modality for patients with node positive disease, in node negative patient’s 3D conformal therapy is as effective as IMRT. Another point Grills makes is that target volume definition becomes more critical with the use of IMRT the use of planning PET scans and administration of i.v. and oral contrast agents when possible should be strongly considered when designing the treatment plan. More studies are needed but IMRT could take over 3D-CRT in the researcher’s clinical department for treatment of NSCLC.

For stages with IIIA- IIIB when surgery is not an option, a chemo-radiation approach is recommended (NHS 2011). Combining chemotherapy with radical radiotherapy has been shown to have survival advantages for patients with stage III disease REF. In addition, chemotherapy prior to radiotherapy may be considered in patients with bulky stage IB and II disease (Ward and Mulvenna 2009). This has been adopted in the researchers department with the chemotherapy being given sequentially or concurrently depending on the patient’s performance status (Department Protocol 2013).

(Laser et al. 2008) Looked at IMRT with chemotherapy, 102 patients with stage III NSCLC were treated with platinum-based chemotherapy and IMRT to doses greater than 50 Gy between 2001 and 2007Patients who received concurrent chemotherapy and IMRT had a 2-year overall survival rate of 57% compared to 44% in those who received sequential chemotherapy and IMRT (p \ 0.01). The main limitations associated with this study were the prescription dose varied between 50-80gy. More critique

CHART

Continuous Hyper-fractionated Accelerated Radiotherapy (CHART) Has been proven to provide an enduring survival advantage for patients with NSCLC when compared to the conventional dose of 60Gy in 30 fractions REF. CHART involves the administration of 54Gy in 36 doses of 1.5Gyeach, delivered 3 times daily over a total of 12 days (Department protocol 2013). Patients with stage I or II NSCLC who are medically inoperable but suitable for radical radiotherapy should be offered the CHART regimen. (NHS 2011), The researchers department indicates that CHART is suitable for stages I-III but must have a WHO performance status of 0 or 1 (Department Protocol 2013).

Stereotactic

Treatments like CHART, 3D-CRT and IMRT are traditionally delivered in small fractions; daily, over multiple weeks. A new treatment modality called Stereotactic body radiotherapy (SBRT) uses large fractions over just a few days (Xia et al. 2006). SBRT has been used successfully in Japan for many years and has only recently been popularized in the United States.  It is an exciting approach given that treatment may be delivered with as few as 3-4 fractions, significantly reducing the need for multiple weeks of radiotherapy. (Haas 2008)

(Xia et al. 2006) Looked at the efficacy and toxicity of SBRT in patients with Stage I/II NSCLC. Xia reported that 3-6 months after treatment a complete response rate was seen in 63% of patients and a overall resonance rate of 93%. With only 2.3% of patients having grade 3 pneumonitis. This was a comprehensive study that produced significant results. SBRT is also showing signs that it could possibly be as effective as surgery for the treatment of stage 1 NSCLC. A study by (Onishi et al. 2011), looked at 87 patients who refused surgery and underwent SBRT at follow up 5 year overall survival rates for stage 1A and 1B were 72% and 62% respectively. Nevertheless a comprehensive randomized trial is needed to conclude whether outcomes of SBRT for medically operable patients are truly comparable to those of surgery. The Northern Lung Cancer Clinical Guidelines (Ward and Mulvenna 2009) state that the researchers department has the technology to deliver SBRT and hope that it will be up and running soon.

A major concern with the treatment of lung cancer with radiation is that many tumours move with respiration. Movement causes increased radiation to normal tissue as larger fields are used to ensure the tumour is not missed.REF

Respiratory gating is a technique that minimises the effect of motion during radiotherapy. This is because radiotherapy is delivered intermittently and delivered during a specific part of the breathing cycle. This limits the amount of dose given to healthy lung tissue (Saito, Sakamoto and Oya 2010)Gating however has several limitations. Treatment planning and set up procedures take a considerable amount of time; furthermore the time to deliver a fraction of RT is increased because the radiation is delivered during only certain parts of the breathing cycle. The ideal solution to this problem would be to track the tumour in real time during treatment and correct the beam position to match the location of the target.

CyberKnife a new type of SBRT that uses real time imaging of the tumour, fiducial markers are placed within the tumour – a revolutionary tracking technology called Synchrony. Throughout treatment, even the slightest movement, such as a patient's breathing, will cause tumour movement. By continuously tracking the position of the tumour and correcting for movement in real time, there is minimal dose to healthy surrounding tissue, including blood vessels, nerves and vital (Brown et al. 2007)

Although CyberKnife is a relative new treatment modality there is some follow up studies showing convincing results. A study by (Brown et al. 2007) looked at 59 patients with stage 1 NSCLC treated with CyberKnife. Of the 59 treated 86% were still alive at the 33month follow up marker. Image-guided robotic stereotactic radio surgery of lung tumours with CyberKnife achieves excellent rates of local disease control with limited toxicity to surrounding tissues and, in many cases, might be curative for patients for whom surgery is not an option. This type of real time adapted radiotherapy is not available at the researchers clinical department but funding has been granted for ‘Cyber Surgery’ to be fully operational by the end of 2013. (newcastle-hospitals.org 2012). This coincides with the NRAG report that "recommends that all replacement and newly installed machines are capable of image guided four-dimensional (4D) adaptive radiotherapy". (Department Of Health 2007)

MDT

Lung cancer MDTs are designed to standardise care and reduce health inequalities. The Northern Lung Cancer clinical guidelines. (Ward and Mulvenna 2009)State that each cancer unit should have a team of members with different disciplines involved in the treatment and management of lung cancer. In which they should meet up fortnightly, the core members attending should be: Respiratory physician with an interest in lung cancer, Clinical and/or medical oncologist, Radiologist, Histopathologist/Cytologist Thoracic surgeon, Lung cancer nurse specialist Palliative care representative..

An interesting study conducted by (Robinson et al. 2008) looked at the effect of lung cancer survival depending wherever the MDT had a Respiratory physician on site. Robinson et al compared two sites one of which had a respiratory physician (Site A), 25 patients were analysed for site A and 28 for site B. Survival for patients at site A was longer, The main conclusion from the study is that Lung cancer patients not under the care of a respiratory physician have fewer interventions and poorer survival .

Conclusion

Lung cancer cancer-related deaths than breast, prostate, and colorectal cancers combined. What is true about SCLC and NSCLC is that once it begins to spread the management options change. Radiotherapy plays a huge part in the treatment of lung cancer, with the advances in SBRT it is hoped that life expectancy for patients with NSCLC will increase, as for SCLC screening programs should be in place to ensure it is caught in its infancy to give the patient the best possible outcome.