**Introductory Chapter: Role of Nuclear Medicine in Medical Science**

## Aamir Shahzad

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.85606

#### **1. Introduction**

The science of nuclear medicine (NM) involves the administration of trace quantities of radionuclide's that are used to provide diagnostic information in a diverse range of diseases. In its most basic form, a NM study comprises of injecting a radiopharmaceutical, a combination of specific pharmaceutical tagged with a gamma-ray-emitting radioactive tracer into the body. There are a number of pharmaceutical available which are used for specific organ imaging. It function is to carry gamma emitting radioisotope into a specific organ. When the radionuclide decays, gamma rays photons are emitted. The energy of these gamma photons is such that a large number of photons are exited from the body without being scattered or attenuated. These photons are later detected by a position-sensitive instruments called gamma camera or scintillation camera and form an image of the distribution of the radionuclide, and hence the compound to which it was attached. There are two classesof nuclear medicine imaging: single photon emission tomography which is essentially a single photon imaging and positron imaging. Single photon imaging usually comprises of either taking a planar image or a series of planar images around the body. A planar image is picture of radionuclide distribution in the patient from one angle. This results in an image having insufficient depth information, but which can still be diagnostically useful. In order to get depth information, data from various views are collected around the patient. This allows cross-sectional images of the distribution of the radionuclide which was later reconstructed employing specialized soft ware's (these software's use highly sophisticated algorithms), thus providing the depth information missing from planar imaging. Positron imaging uses radionuclide that decay by positron emission. The emitted positron usually has a very short lifetime and produces two high-energy photons after interacting with its counterpart electron. The two simultaneously emitted gamma photons having energies of 511-KeV subsequently are detected by an imaging

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


**Table 1.** Physical properties of PET scintillators.

 camera. Once again, topographic images are formed by collecting information from different angles around the patient, resulting in PET images; however detectors remain stationary and do not move around the patient as it happens in SPECT study. A list of physical properties of different types of scintillator used in nuclear medicine is described in **Table 1**. It is clear from the table the GSO and LSO are quite fast materials with the decay time of 60ns and 40ns and are most suitable for PET time of flight measurements. However, NaI (Tl) detectors are more sensitive and give strong output per unit absorption of energy.

Although the amount of radioactive tracers injected into the patient is very small, however, smaller quantities carry risk and therefore assessment of absorbed dose to the organs and whole body become essential. Considerable work has been done internationally so far on the assessment of dose to remnant thyroid tissue and whole body. A high level of radioactivity is usually prescribed in routine to ablate thyroid tissue, therefore, its accurate quantification as well as safety of radiation technologists is a must. Different methods of measuring activity while in shielding were proposed to reduce the extra radiation burden to allied radiation staff. Before giving therapeutic radioiodine, uptake in the thyroid tissue is determined using uptake system that provides an estimation of the remnant thyroid mass. The uptake value is a value that can be reproduced with great accuracy and same will also be made sure that the uptake value is reproducible. Currently the clinical practice of administering radioactivity to treat Differentiated Thyroid Cancer (DTC) varies widely from hospital to hospital and ranges from 1110 to 3700-MBq or even more. This increase in activity although does not confer any therapeutic benefits to the patients. The corresponding absorbed dose to thyroid mass also varies widely from (13–1161) Gy depending on the mass of the remnant thyroid tissue, dose rate and the absorbed cumulated activity. The whole body receives, in this case, an absorbed dose of 0.12–0.23-Gy. Since the radioiodine is a non-specific agent, it also deposits in other parts of the body giving unnecessary radiation dose for example breast, liver, etc. This is particular of important for lactating women. The empirically determined activity without any apparent correlation between absorbed dose and activity depends solely on the experience of the individual groups and can varies by an order of magnitude from the standard practice. High success of non-scientific approach was reported, however, 15% of patients with high-risk DTC have significantly reduced life expectancy even after getting treatment using conventional approach of fixed amount of administered activity. The fixed-activity approach without assessing pretherapeutic lesion absorbed dose and toxicity assessment generally results in administration of low amount of therapeutic radiodine as compared to with absorbed dose assessment. In this era of personalized and precision medicine, individualized approach to treatment will bring more patient benefits and improve life expectancy. The quantity of activity should be given to patient that is right and as high as safely achievable (AHASA) [1–5].

#### **2. Conclusions**

Diagnostic reference levels (DRLs) and achievable doses (ADs), a form of investigation- levels, represent an important tool in medical imaging as optimizing the radiation dose- delivered to patients. It is essential to ensure that the appropriate clinical information is

available in the image throughout the optimization process. In order to implement optimization process, both patient dose and clinical utility must be taken into account depending- on image quality.

#### **Acknowledgements**

The authors thank Dr. Sajid Bashir (Principal Scientist, Punjab Institute of Nuclear Medicine (PINUM) Faisalabad, Cancer Hospital, Pakistan) for providing his useful discussions and suggestions.

## **Abbreviations**


#### **Author details**

Aamir-Shahzad-

Address all correspondence to: aamirshahzad\_8@hotmail.com-

Molecular Modeling and Simulation Laboratory, Department of Physics, Government College University Faisalabad (GCUF), Faisalabad, Pakistan

#### **References**

[1]-I.C.R.P. 1990 recommendations of the international commission on radiological protection. Annals of the ICRP. 1991;**21**(1-3):123-127-


**Chapter 2**

**Provisional chapter**

**Radiation Therapy in Metastatic Neuroblastoma**

**Radiation Therapy in Metastatic Neuroblastoma**

DOI: 10.5772/intechopen.80892

Neuroblastoma is the commonest extracranial solid tumor in children, and metastasis at presentation is seen in more than 50% of cases. The role of radiotherapy as a palliative modality in patients with advanced neuroblastoma provides better symptomatic relief. Palliative radiotherapy dose schedules can be given either in single hypofractionation from 4 to 8 Gy or fractionated radiotherapy that can range from 21 to 30.6 Gy. Doseresponse relationship trend has been reported in the palliative setting of bone metastasis. Because of the proximity of tumor to critical organs, serious adverse effects can be avoided with conformal techniques. Although currently there is limited data available, new treatments with particle therapies are undergoing clinical evaluation and may offer

Rudolf Virchow, a German physician, was the first person who described neuroblastoma in 1864. Through his research he called the tumors found in the abdomens of children as gliomas. In 1910, James Homer Wright made great efforts to map the origin and development of tumor cells, and he named the tumors neuroblasts, as "blastoma" refers to a collection of immature, undifferentiated cells [1]. His meticulous study showed that these tumors originated from an immature, primitive form of neural cell. The term *neuro* denotes to "nerves," while *blastoma* denotes to a "cancer that affects immature or developing cells." Neuroblasts which are formed during embryonic stages develop normally once fetus matures after birth. Sometimes due to uncontrolled cell divisions, they become cancerous, causing neuroblas-

> © 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use,

distribution, and reproduction in any medium, provided the original work is properly cited.

Meenu Gupta and Anupam Dhasmana

Meenu Gupta and Anupam Dhasmana

http://dx.doi.org/10.5772/intechopen.80892

**Abstract**

**1. Introduction**

toma (**Figure 1**).

Additional information is available at the end of the chapter

Additional information is available at the end of the chapter

new hope for good quality of life in these patients.

**Keywords:** neuroblastoma, radiotherapy, palliative, metastasis, dose

## **Radiation Therapy in Metastatic Neuroblastoma**

#### Meenu Gupta and Anupam Dhasmana

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.80892

#### **Abstract**

Neuroblastoma is the commonest extracranial solid tumor in children, and metastasis at presentation is seen in more than 50% of cases. The role of radiotherapy as a palliative modality in patients with advanced neuroblastoma provides better symptomatic relief. Palliative radiotherapy dose schedules can be given either in single hypofractionation from 4 to 8 Gy or fractionated radiotherapy that can range from 21 to 30.6 Gy. Doseresponse relationship trend has been reported in the palliative setting of bone metastasis. Because of the proximity of tumor to critical organs, serious adverse effects can be avoided with conformal techniques. Although currently there is limited data available, new treatments with particle therapies are undergoing clinical evaluation and may offer new hope for good quality of life in these patients.

**Keywords:** neuroblastoma, radiotherapy, palliative, metastasis, dose

#### **1. Introduction**

Rudolf Virchow, a German physician, was the first person who described neuroblastoma- in 1864. Through his research he called the tumors found in the abdomens of children as gliomas. In 1910, James Homer Wright made great efforts to map the origin and development- of tumor cells, and he named the tumors neuroblasts, as "blastoma" refers to a collection of immature, undifferentiated cells [1]. His meticulous study showed that these tumors originated from an immature, primitive form of neural cell. The term *neuro* denotes to "nerves," while *blastoma* denotes to a "cancer that affects immature or developing cells." Neuroblasts- which are formed during embryonic stages develop normally once fetus matures after birth. Sometimes due to uncontrolled cell divisions, they become cancerous, causing neuroblastoma (**Figure 1**).

© 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

**Figure 1.** Primordial neural crest cells which develop into the adrenal medulla and sympathetic ganglia during specification and differentiation that lead to formation of neuroblastoma. Adrenal gland is the most common site of origin, but sympathetic nervous system chain from the neck to the pelvis can be other common site of origin.

## **2. Epidemiology**

This set of tumors is considered almost exclusively a disease of pediatric population. Neuroblastoma is the most common solid extracranial tumor, accounting for third most common childhood cancer, after leukemia and brain tumors. Neuroblastoma accounts for approximately 15% of all pediatric cancer fatalities with almost 600 new cases are diagnosed in the United States each year. White race infants displayed more incidence of neuroblastoma than black infants (ratio of 1.7:1 for male and 1.9:1 for females), but little of any racial difference is apparent among older- children. Males have higher incidence rate relative to females (male-to-female ratio of 1.3:1) [2]. Neuroblastoma is thought to occur sporadically, with 1–2% of cases are familial [3].

#### **3. Clinical presentation**

Patients with neuroblastoma present with a combination of signs and symptoms which are nonspecific and are variable. They depend on site of tumor, size, degree of metastatic spread, and catecholamine secretion.

#### **3.1. Primary disease**

Neuroblastomas in the abdomen are the most common form that arises in 65% of cases, approximately 50% arises from the adrenal glands (adrenal neuroblastoma), and one-third are from paravertebral ganglion (extra-adrenal neuroblastoma). Abdominal mass which is asymptomatic may be an incidental finding which is usually detected by parents [4].

Symptoms are abdominal pain or fullness and abdominal mass which is usually firm and fixed.- Characteristic nodularity of abdominal neuroblastomas is similar to palpating a *bag of potatoes* 

which differentiates it from a nephroblastoma. In some cases, enlarged liver, spleen, and intestinal obstruction may be seen. Rarely, scrotal and lower extremity edema results from the compression of venous and lymphatic drainage of the lower extremities due to size of primary or metastatic abdominal tumors. Renin-mediated hypertension is because of compromised renal vasculature. Epinephrine is rarely released from most neuroblastomas due to deficiency of enzyme necessary for synthesis. So hypertension, tachycardia, flushing, and sweating are uncommon symptoms. Hypertension and opsomyoclonus detected in less than 2% are part of paraneoplastic syndromes [5].

#### **3.2. Metastatic disease**

More than 50% of patients present with metastatic disease. Neuroblastoma is associated with lymphatic and hematogenous spread. Common hematogenous metastatic sites are the bone marrow (70.5%), bones (skull, long bones, ribs, vertebrae, 55.7%), liver (29.6%), and skin and rarely the brain or lungs. Thirty-five percent of patients had regional lymph node metastases with localized tumors [6].

#### *3.2.1. Signs and symptoms of metastasis*

Long bone involvement causes pain and limping with increasing risk of pathological fractures which is known as Hutchinson syndrome. Periorbital ecchymoses, swelling, and proptosis (raccoon eyes) occur due to sphenoid bone and retrobulbar tissue involvement. Painless proptosis, periorbital edema, and ecchymosis of the upper lid are akin with trauma or child abuse. Irritable and fussy infant needs attention. Bone marrow involvement may result in pancytopenia. Huge involvement of the liver in metastatic condition is common in infants with stage Ms/4S and may cause Pepper syndrome (PS), which induces the respiratory distress, quoted by W.-Pepper [7]. PS was recognized as a localized primary tumor and metastatic condition restricted to the skin, bone marrow, and liver in infants. PS is usually known for better prognosis, as it is linked with spontaneous regression of disease. Some infants with stage 4S neuroblastoma die of massive hepatomegaly, respiratory failure, and overwhelming sepsis. Non-tender, bluish, and mobile skin and subcutaneous nodules are because of metastasis to these sites. This is known as "blueberry muffin sign." These nodules become

**Figure 2.** Spinal cord compression by vertebral body metastasis and extension of tumor posteriorly into the epidural space.

prominently red once provoked and thereafter blanch for some minutes, due to release of vasoconstrictive metabolic products. These nodules can be diagnostic of neuroblastoma and should be differentiated from metastatic skin leukemic infiltrates.-

Paraspinal tumors in the thoracic, abdominal, and pelvic regions often present with spinal cord compression due to spinal canal invasion through the neural foramina causing symptoms related to compression of nerve roots and spinal cord. There may be subacute or acute paraplegia, bladder or bowel dysfunction, or less commonly radicular pain. Cervical neuroblastoma may present as Horner's syndrome [8] (**Figure 2**).

#### **4. Prognosis according to MYCN amplification status-**

 In infants, MYCN (neuroblastoma-derived, v-myc avian myelocytomatosis viral related oncogene) amplification and unfavorable Shimada histopathology correlated with increased frequencies of bone and intracranial or orbital metastases. In geriatric patients, MYCN amplification is associated with increased risk of intracranial or orbital and lung and liver metastases [6]. MYCN amplification status defines response rate to palliative radiotherapy. Median overall survival time is increased in patients without amplification. A French study showed response rate to palliative RT according to MYCN status was 47.6% in patients with amplified MYCN vs. 75.7% in patient without amplification of MYCN (*p* =-0.04) [6, 9].

## **5. Investigation**

Medical history including family history and physical examination is needed before proceeding for any investigations.


#### **6. Staging**

Most commonly used system is the International Neuroblastoma Staging System (INSS) based on clinical, radiographic, and surgical findings (see **Figure 3**).

**Figure 3.** The International Neuroblastoma Staging System (INSS) [10, 11].

**Figure 4.** Showing the International Neuroblastoma Staging System (INRGSS) [10, 11].

Later, the International Neuroblastoma Risk Group Staging System (INRGSS) and International Neuroblastoma Risk Group Consensus Pretreatment Classification are released.- INRGSS is using pretreatment tumor imaging rather than extent of surgical resection [10]. The INRGSS is explained in **Figure 4**.

#### **7. Management**


#### **7.1. Radiotherapy**

In high-risk neuroblastoma, radiation therapy (RT) can be recommended both to the primary site and to sites of metastatic disease as part of consolidative therapy. RT also plays an integral part in the palliation of symptoms from metastatic disease. RT can be used to treat emergencies such as:


#### *7.1.1.1. Three-dimensional conformal radiation therapy*

 Three-dimensional conformal radiation therapy (3DCRT) is considered the gold standard practice to treat metastases. Conformal dose distribution to the target volume and dose reduction to the surrounding normal tissues is achieved by 3DCRT. In 3DCRT planning, after making the patient comfortable and in reproducible position, adequate immobilization is done by immobilization devices. Three-dimensional anatomic information is obtained on CT simulator or MRI. Three-dimensional conformal plans are generated to deliver high doses within the tumor which is the target and spare the adjacent normal structures at the same time. In the case of vertebral metastasis, radiation portals should include the involved vertebral body (and the soft tissue if involved by the tumor), plus a vertebral body below and above. Patients can be treated in either supine or prone position. If bony metastatic sites are very painful and there is difficulty in prone position, patient can be made comfortable in supine position, and this is also an acceptable reproducible position. A three-dimensional plan composed of one anteroposterior field and two posterior oblique wedged field is illustrated in **Figure 5**. The dose prescribed is 20 Gy at 4 Gy per fraction. Hypofractionated radiotherapy is minimally toxic and time efficient for palliation purpose.-

#### *7.1.2. Treatment volumes*

Delineation of target volumes is done by CT-based planning. The gross tumor volume of the primary (GTVp) should include post-induction chemotherapy and presurgical disease. For abdominal primaries, the clinical target volume (CTVp) included the para-aortic lymph nodes in addition to the GTVp. Setup uncertainties are reduced by the generation of planning target volume (PTVp) through expansion of the CTVp approximately 0.5–1.0cm. For metastatic sites irradiation, the GTVm consisted of the residual metastatic tumor (following induction chemotherapy) as defined by MIBG, CT, or MRI.-An additional 1.0–1.5cm CTVm margin for microscopic disease followed by a 0.5–1.0 cm PTVm margin will account for setup uncertainties.

**Figure 5.** Isodose distribution for three-dimensional conformal radiotherapy (3DCRT) to vertebra.

The 6MV photon energy is delivered by linear accelerator. Wedges and compensators are used to make the dose distribution more uniform. Whole PTV should be included within the 95% isodose surface. Not >10% of the PTV should achieve >110% of the prescription dose (evaluated by DVH) [12].

 If dose prescription is 21.6 or 36-Gy, then constraints defined by ANBL0532 AOR are the contralateral kidney in which V12 should be <20% and V8 < 50% and the liver in which V9 should be <50% and <25% to receive 18 Gy. With these conservative doses, Kandula et al. did not observed any hepatic or renal toxicity [12].

When treating a child with intensity-modulated radiotherapy (IMRT) techniques, the theoretical increase in secondary malignancies should be considered. For volumes exposed to low-dose RT, IMRT significantly increased the normal tissue volume receiving 50% or less of the prescribed dose for the volumes exposed to low-dose RT. The decision to irradiate a metastatic site should be made by the treating physician depending upon the evaluation based on post-induction response and posttransplant or preradiotherapy imaging.-

#### *7.1.3. Radiotherapy doses*

Most of the studies recommend that the median RT dose to the primary site is 21.6 Gy (range 21.0–30.6-Gy). Metastatic sites can be irradiated concurrently with the primary site [13]. The median RT dose recommended to metastatic sites is 21.6 Gy (range 21.0–30.6 Gy) in 12 fractions [12]. Casey et al. reviewed results of RT to metastatic sites as a part of consolidative therapy at a single institution between 2000 and 2015. Among 159 patients, 229 metastases were irradiated. Median dose of 21 Gy (10.5–36 Gy) was given to 90% of irradiated metastasis. Out of 229 irradiated metastasis, 35(15%) had tumor recurrence. These irradiated metastatic sites had 81.3% 5-year local control. There was no difference inlocal control as far as number of metastatic sites is irradiated. Also the site of metastatic bone versus soft tissue irradiation had no impact on local control, but there was improved overall survival (OS) 59.5% seen in

 cases who were controlled at metastatic site than those patients whose disease was persistent, and OS in these patients was 18.3% with p-=-0.0003 [14].

#### *7.1.3.1. Response rate in palliative radiotherapy*

RT is effective in controlling metastatic deposits and in decreasing symptoms due to metastatic disease, with a response rate of 65.2% observed in various studies. Response rates varied with the type of metastases: 84.2% in soft tissue metastases and 63.2% in bone metastases [9].

#### *7.1.4. Bone metastases*

There are many established fears about the long-term impact of RT in children like growth disturbances or other skeletal abnormalities after irradiation of the musculoskeletal system. Radiotherapy is performed primarily in these patients with incurable or metastatic disease to relieve pain, definitely control a bone affected from metastases, and prevent pathologic fractures as well as spinal cord compression.

#### *7.1.4.1. Radiotherapy doses for bone metastasis*

Dose schedule ranges from 6 to 40-Gy [9]. Fraction regimens can be given from 1.8 to 4-Gy per fraction. The most commonly irradiated sites reported are the lower limb (34%) and spine (29%). An overall response rate of 65–77% is reported in various studies [9, 15, 16]. The Institut Curie, Paris, France, published a series of 23 children with neuroblastoma treated for 38 bony metastatic sites with doses ranging from 6 to 40 Gy. A trend toward improved response with higher doses was seen (**Tables 1** and **2**) [9].

#### *7.1.5. Soft tissue metastasis*

In soft tissue metastasis, mediastinum, supraclavicular, cervical, axillary, abdominal, and orbital sites are often involved**.** 

#### *7.1.5.1. Fractionation schedule*

The optimal fractionation schedule is still an unresolved issue. Doses can be given as 20 Gy, with a range from 8 to 36-Gy [9]. Various fraction regimens, including 1.5–4 Gy per fraction, can be given in palliative setting. **Figure 6**(**a** and **b**) illustrates 3DCRT radiotherapy treatment of olfactory neuroblastoma with extension into maxillary sinus, ethmoid, orbital, and neck nodes metastasis.


**Table 1.** Response to radiotherapy according to dose delivered for bone metastases.


**Table 2.** Response to radiotherapy in 23 patients with bone metastasis according to MYCN status.

**Figure 6.** (a and b) Isodose distribution for three-dimensional conformal radiotherapy (3DCRT) to the nose, orbit, right maxilla (**Figure 6a**), and ipsilateral neck (**Figure 6b**) with wedge for homogenous dose distribution. Blue represents 95% of the isodose line.

#### *7.1.6. Radiotherapy for hepatomegaly (stage 4S)*

Massive hepatomegaly causes respiratory distress. To prevent respiratory compromise, the liver is irradiated for symptomatic stage 4S disease. Doses can be given as 450–600 cGy in 2–4 fractions (450cGy in 3 fractions, 1.5-Gy/fraction) [15]. Target volume can be treated by opposed lateral fields to avoid renal and ovarian exposure.-

#### *7.1.6.1. Radiotherapy borders*

Radiotherapy box field should be gridded as anterior border 2cm anterior to the liver, posterior border should be anterior to vertebral body, superior border 2 cm superior to the liver, and inferior border gridded at superior iliac crest to avoid ovarian exposure.

Although very rare but one study reported by Paulino showed survival of one patient stage 4S neuroblastoma with liver metastases who was alive 13years after hepatic irradiation [15].

#### *7.1.7. Intracranial metastasis of neuroblastoma (IMN)*

CNS lesions are defined as leptomeningeal disease or metastatic deposits in the CNS parenchyma. Patients with radiographic evidence of bone involvement or with intracranial extension from the epidural, dura, or skull are not classified with CNS neuroblastoma. Patients who experience a disease recurrence incidence of leptomeningeal or CNS parenchymal disease range from 1 to 16%. The overall incidence rate for newly diagnosed patients is approximately 6.3%. The incidence rate is >10% in cases who are treated with recent intensive chemotherapy and immunotherapy (N6 and N7, with which the expected cure rate is ≥38%) [17].

Symptoms of CNS involvement are listed in **Box 1**. Patients with neurologic symptoms should undergo physical examination and further neuroimaging with head/orbit CT and/or MRI scans. MIBG scan is not a reliable indicator of CNS disease as false-negative MIBG scans appear to be common for patients with CNS lesions. This is due to difficulty in discriminating CNS lesions from skull lesions without SPECT images.


**Box 1.** Clinical features of patients with central nervous system involvement.

#### *7.1.7.1. Genetic associations in brain metastasis*

Neuroblastoma tumors that exhibited MYCN amplification correlate with high-risk disease and poor prognosis as they developed CNS recurrence.

#### *7.1.7.2. External beam radiotherapy in CNS metastasis*

Prognosis is very poor even if multimodality treatment is given. Multiple brain metastasis can be treated by whole brain radiotherapy. In patients with oligometastasis in the brain, literature suggested that stereotactic radiosurgery (SRS) confers survival benefit [18].

#### *7.1.8. Gamma knife radiosurgery*

 Nathan C. Rowland et al. described in literature two cases of the application of SRS to high-risk, recurrent IMN. Leksell Gamma Knife model 4C using Leksell GammaPlan 4C treatment planning software was used for radiotherapy. First patient 5-year-old male was treated case of neuroblastoma whose brain magnetic resonance imaging (MRI) showed a 4.0-×-3.3 cm mass in the- right parietal lobe with a small amount of surrounding edema and midline shift. The dose prescription was 27.7 Gy to 47% isodose line. The 18 mm and 14 mm collimating helmets were used in 18 targets. Target volume was 29.2 cc and 100% target coverage was by prescribed isodose line. Conformity index of 1.34 was achieved. Radiological follow-up at 2 and 4 months revealed stable reduction of disease. Patient again received chemotherapy and 21.6 Gy dose given to craniospinal axis. Three-month post-radiotherapy intra-ommaya therapy along with complete surgical excision of mass was given. CNS relapse occurred 15 months after radiotherapy and

 patient gave up to disease. The second case was 2 ½-year-old male treated case of neuroblastoma which showed solid mass in the left parieto-occipital lobe measuring 1.8-×-1.0 cm with a- small anterior cystic component. Stereotactic biopsy of the intracranial mass diagnosed the neuroblastoma. A dose of 14 Gy was prescribed to the 50% isodose line and this was administered- to five targets. The 18 mm collimating helmet was utilized. Although radiological follow-up at 2- and 3months showed reduction in size of initial parieto-occipital lesion, 4-month follow-up CT- scan showed slight progression in size of metastatic lesion with vasogenic edema. Finally after- CNS relapse which occurred 7 ½-month post-radiotherapy, patient died of disease. Stereotactic radiosurgery is an acceptable palliative method in the treatment of IMN [19].

#### *7.1.9. Proton beam therapy*

Proton beam therapy (PBT) is a good alternative to photon therapy for pediatric patients where post-radiotherapy side effects are concerned. PBT delivers radiation within a defined radiation track length, with virtually no dose beyond the intended target due to Bragg peak (**Figures 7** and **8**). Proton beam provides superior target volume coverage and greater dose reductions for normal tissues or organs at risk by a factor of 1.5–3.0 than photon beam. This is due to additional benefit of no exit dose and low entrance dose [20]. Proton beam is considered safe for neuroblastoma pediatric patients with minimal risk of secondary cancer which is slightly higher with intensity-modulated radiotherapy (IMRT) due to peripheral doses. As discussed earlier, doses in path of proton beam are very minimal. There is homogenous dose distribution with large volume of neuroblastoma with less number of ports than IMRT [21].

#### *7.1.10. Procedure*

Before treatment, CT images for PBT planning are to be obtained at intervals of 2–5 mm in the treatment position. The interval depends on the age, height, and treatment site of the patient. The gross tumor volume (GTV) is defined as the tumor volume before PBT for a recurrent tumor. The clinical target volume (CTV) is defined as the GTV plus a 1.5cm margin, and the PTV is defined as the CTV plus a 0.5–0.7cm margin. Toxicity and treatment effect should be

**Figure 7.** Bragg peak of proton is very sharp.

**Figure 8.** Sharp reduction of dose to brain tissue by proton irradiation.

balanced in determining the CTV. Sedatives can be administered for planning CT and treatment in pediatric patients.

 The photon equivalent dose (GyE)-=-[Physical Dose (Gy)] × [Relative Biological Effectiveness of the proton beam]. This is assigned with a value of 1.1.

 The PBT doses usually administered from 19.8 to 45.5 GyE (median: 30.6-GyE)-[21].

#### **8. Summary**


Dose constraints for liver normal parenchyma are V9 Gy <50% and V18 Gy <25%; contralateral kidney constraints are V8 Gy <50% and V12 Gy <20%.

#### **Acknowledgements**

We gratefully acknowledge Dr Vijay Dhasmana, the Honorable Vice Chancellor of Swami Rama Himalayan University, Dehradun, India, for his support and for providing the necessary facilities, and we are also thankful to Prof. (Dr) Sunil Saini, Director of Cancer Research Institute, Chairman Research Committee, Himalayan Institute of Medical Sciences, Swami Rama Himalayan University and Prof. (Dr) Mushtaq Ahmad, Dean, Himalayan Institute of Medical Sciences, Swami Rama Himalayan University, Dehradun.

#### **Conflict of interest-**

We have no conflict of interest with anybody working in the area and among the authors in the book chapter.

## **Author details**

Meenu Gupta1 \* and Anupam Dhasmana2

\*Address all correspondence to: meenugupta.786@rediffmail.com-

1-Department of Radiation Oncology, Cancer Research Institute, Swami Rama Himalayan University, Dehradun, India

2 Department of Biosciences, Swami Rama Himalayan University, Dehradun, India

#### **References-**


**Chapter 3**

**Provisional chapter**

**Effect of Low Dose (Diagnostic X-Rays) on Peripheral**

**Effect of Low Dose (Diagnostic X-Rays) on Peripheral** 

Exposure to ionizing radiation is known to affect some hematological parameters of biological sample. This study was aimed at evaluating the effect of ionizing radiation within the diagnostic range on some hematological parameters in guinea pigs. Thirty six (36) apparently healthy adult guinea pigs of both sexes weighing between 700 and 1200 g were used. The guinea pigs were categorized in to three groups, 12 per group; group A (control), group B, and C were exposed to X-rays within the diagnostic range, using 70 kV and 12.5mAs; using X-ray machine MS-185, serial no. 0904 GE at a source to skin distance (SSD) of 90 cm. Blood samples were collected from all the guinea pigs at intervals of 1, 24, 72, 168 and 336 hours post-irradiation, and subjected to standard hematological analysis. A continuous decline in the mean total white blood cell count and mean lymphocyte, monocyte, neutrophil and eosinophil count after 1 hour in both groups was observed, and more pronounced after 24 hours post-irradiation. However, stability was observed 72 hours post-irradiation in both groups. In conclusion, a depleting effect of low dose ionizing radiation on white blood cell count was found, with appreciable recovery occurring after 72 hours onward. **Keywords:** white blood cell, irradiation, guinea pigs, ionizing radiation, hematological

> © 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use,

distribution, and reproduction in any medium, provided the original work is properly cited.

Radiation is a wave or particle traveling through space which can transmit all or parts of its energy on contact with matter [1]. It could be ionizing and non-ionizing in nature [2].

DOI: 10.5772/intechopen.80417

**White Blood Cells Count in Guinea Pigs (***Cavia*

Geofery Luntsi, Victory S. Daniel, Chigozie I. Nwobi and

**White Blood Cells Count in Guinea Pigs (***Cavia* 

*porcellus***)**

Bura T. Paul

**Abstract**

parameters

**1. Introduction**

*porcellus***)**

Geofery Luntsi, Victory S. Daniel, Chigozie I. Nwobi and Bura T. Paul

http://dx.doi.org/10.5772/intechopen.80417

Additional information is available at the end of the chapter

Additional information is available at the end of the chapter
