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Table of Contents
REVIEW ARTICLE
Year : 2018  |  Volume : 1  |  Issue : 1  |  Page : 29-34

Approach towards re-irradiation of common cancers


1 Department of Radiotherapy, Medical College, Kolkata, West Bengal, India
2 Department of Radiation Oncology, Mahatma Gandhi Cancer Hospital and Research Institute, Vishakapatnam, Andhra Pradesh, India

Date of Web Publication18-Jun-2018

Correspondence Address:
Dr. Anis Bandyopadhyay
Room No. 15, Department of Radiotherapy, Medical College and Hospital, 88B College Street, Kolkata - 700 073, West Bengal
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jco.jco_7_17

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  Abstract 


Reirradiation, in combination with systemic therapy or biologicals, in recent years, has become a popular option for locally recurrent cancers and for infield second malignancies in cases where surgical salvage is not feasible. However before embarking onto such a course of second radiation a systematic approach is needed to avoid undesirable consequences and to gain meaningful advantage in terms of survival and local control. An decision making approach for common cancers where re-irradiation is commonly used like the head and neck cancers, the gliomas and in cases of gynecological cancers has been discussed. Proper selection of the cases and the choosing the intention for re-irradiation is probably most important initial step. Care of the details of the initials course of radiation like the dose fractionation schedule, volume irradiated, dose to the Organs at risk along with patient's present general condition is of utmost importance. Issues like dose memory, threshold time interval, maximum effective cumulative dose etc are still areas of research and their importance in each individual site needs to ascertain in future. Finally, the aim is to have a perceived benefit over the potential of harm in a successful course re-irradiation.

Keywords: Gynaecological cancers, glioma, head and neck cancers, reiiradiation, recurrent


How to cite this article:
Bandyopadhyay A, Patro KC, Basu P, Roy K. Approach towards re-irradiation of common cancers. J Curr Oncol 2018;1:29-34

How to cite this URL:
Bandyopadhyay A, Patro KC, Basu P, Roy K. Approach towards re-irradiation of common cancers. J Curr Oncol [serial online] 2018 [cited 2018 Nov 15];1:29-34. Available from: http://www.journalofcurrentoncology.org/text.asp?2018/1/1/29/234547




  Introduction Top


The advancement of treatment modalities in surgery, chemotherapy, and radiotherapy (RT) has improved survival rate and locoregional control at many sites of cancer occurrence. However, in-field cancer recurrence after RT and second primary tumors occurring in previously irradiated area are common clinical challenge. Moreover, prognosis is poor when a recurrent or new primary cancer develops in an area previously treated with radiation.[1],[2] In the absence of distant metastatic disease, salvage surgery provides a durable disease control in approximately a small percentage of such patients. In most others where salvage surgery is not feasible or challenging, irradiation, alone or combined with chemotherapy or biological therapy, as an organ-preserving modality plays an important role in the treatment of such cancers.[3] Although reirradiation was in common practice as early as in the early 20th century, in the recent years, there is an increasing interest among radiation oncologist toward delivering a second course of radiation to patients who develop second primary tumors within or close to previous RT portal or late in-field recurrences. This is mainly due to the availability of different modalities of radiation and technology for more and more precise radiation therapy.[4] However, such rational treatment decisions demand not only appreciation of the relevant clinical, pathological, and technical aspects but also rather precise knowledge on the long-term recovery of occult radiation injury in various organs.[1],[5] Finally, proper counseling of the patient about the expected benefit and the potential hazards may help to make an informed choice to proceed for reirradiation.

One of the major issue remains that whether reirradiation toxicity outweighs the potential benefits, considering that the median survival of reirradiated patients marginally exceeds the benefits observed with chemotherapy or other systemic therapy alone in many instances. However, full-dose reirradiation is often a viable treatment option for cancer sites, offering long-term survival for selected patients. The success of full-dose reirradiation depends on a variety of factors such as the initial cancer stage, type of initial treatment (radiation dose, technique, dose per fraction, use of concurrent chemotherapy), response to initial treatments, clinically apparent late effects from initial RT, residual radiation tolerance of the normal tissues, the duration of the relapse-free interval, the comorbidities, and dose fractionation of the reirradiation course [Table 1].[6],[7] Hence, careful selection of cases and judiciously use of the appropriate technology, optimal dose fractionation for the second course of radiation is warranted for meaningful gain in survival keeping the risk for severe radiation-induced morbidity to the minimum possible. An attempt is made in this article for a systematic approach to the decision-making for irradiation of patients with cancers of various sites that are commonly considered for re-irradiation [Figure 1].
Table 1: Prerequisites for reirradiation

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Figure 1: General approach for reirrradiation

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  Head-and-Neck Cancers Top


Locoregional failure is the most frequent pattern of failure in locally advanced head-and-neck cancer patients, with nearly half of the cases failing locoregionally within 24 months. For nonnasopharyngeal head-and-neck cancers, this high rate of locoregional failure was irrespective of the treatment received as evident from the two large RT oncology group (RTOG) trials (RTOG 90-03 and RTOG 91-11). Thus, the head and neck region is one of the most common sites where re-irradiation is increasingly being considered; owing to this high local failure rates and the complexity of salvage surgery [Table 2]. Although the basic guideline to approach toward remains same [Figure 1], one should keep in mind the major prognostic factors that affect the results of reirradiation. Since there are a lot of vital organs in close proximity retreatment with radiation without judicious selection may increase risk of serious toxicity and impaired quality of life with an uncertain survival advantage.[7]
Table 2: Basic rules of reirradiation

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An informed choice has to be made by the oncologist and the patient after discussing the expected benefit and the potential morbidity outcomes [Table 3]. Apart from the various tumor-related factors, the presence of comorbidities and preexisting organ dysfunction (like nonfunctional organ, nonhealing ulcers, acute and chronic dysphagia, trismus/fibrosis, osteoradionecrosis, and carotid rupture) are probably the most important factor before deciding on a course or reirradiation in the head-and-neck region.[6],[7],[8],[9] The cumulative lifetime dose to organs such as the spinal cord, brain stem, and parotids needs to be respected. Wherever possible, intensity-modulated RT (IMRT) should be preferred for its obvious dosimetric advantages over conventional or three-dimensional conformal radiation techniques which transfer into clinically measurable benefits in terms of acute and late toxicity. Advanced radiation techniques, such as tomotherapy or proton-beam therapy, may facilitate treatment near the base of the skull, whereas for small-volume mucosal recurrence, interstitial brachytherapy should always be tried.[10] The reirradiation treatment plan and the intended dose prescription should be decided after careful evaluation of the treatment volume, prior dose distribution and the modality of previous treatments. Care should be taken to minimize the volume of overlap of the two treatment schedules.[6],[10] For treatment near the carotid artery, Doppler ultrasound before reirradiation is often recommended as patients with significant stenosis can be considered for an appropriate vascular intervention before reirradiation. Use of concurrent chemotherapy wherever may possibly improve the chance of survival in most cases.[11],[12],[13] Tumors that recur or persist despite aggressive prior chemoradiation therapy imply the presence of the chemo-RT-resistant clonogens; novel targeted radiosensitizing agents with conformal high-precision radiation are required to overcome the resistance. Provision of aggressive nutritional support during the course of irradiation and after in cases of organ dysfunction is essential to minimize treatment breaks.[14] A curative dose of 50–60 Gy should be attempted with IMRT to the new clinical target volume and efforts should be made to minimize the cumulative spinal cord dose to as low as reasonably achievable. Care should also be taken to keep the reradiation dose to the salivary glands to <25–30 Gy [Table 4].
Table 3: Steps for reirradiation process

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Table 4: Common dose fractionation and concurrent regimens used for reirradiation for different sites

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  Gliomas and Other Brain Tumors Top


Local recurrence of malignant glioma is a common problem in clinical practice. A standard management regimen for recurrence does not exist. The various options available are resurgery, RT, systemic therapy, and the best supportive care. However, the decision depends on the specific patient- and tumor-related factors. Re-resection not only improves symptoms and maintains the quality of life, but also delays symptom progression, reduces corticosteroid doses, and improves response to (and allow intra-operative) chemotherapy and/or RT.[15],[16] Young patients, with Karnofsky performance status (KPS) more than 80%, small volume residual lesion involving noneloquent areas are the ideal candidates for surgery.[17] Reirradiation is an option for a small subgroup of selected patients. The first and foremost step before reirradiation is establishing recurrence and differentiating from pseudoprogression [Table 3]. Patients with a KPS greater than 60%, a tumor size of up to 40 mm, and progression more than 6 months from time of surgery appear to be the best candidates.[15] The most common approach involves the use of fractionated stereotactic RT with or without intensity modulation and a median total dose of 30–36 Gy. Stereotactic radiosurgery and interstitial brachytherapy are not favored because of their high concern for toxicity (20%–30%) and its suitability for very small tumors (<30 cc volumes).[17],[18] Effort should be made to keep the cumulative EQD2 around 100 Gy with conventional technique and slightly higher with conformal and stereotactic RT.[19] The increasing conformity of the reirradiation plan helps in reducing the interval period before reirradiation may be attempted. Using conventional RT after a median interval of 30 months approximately, a cumulative EQD2 of 90–97 Gy can be safely attempted as compared with the use of fractionated stereotactic RT, which allows to attempt further higher doses to a cumulative EQD2 of 110 Gy [Table 4].[20]


  Gynecological Cancers Top


Although the improvement of external beam RT and brachytherapy techniques and increase in dose delivered to the pelvic tumors have improved local control, local pelvic recurrence after RT still occurs in about one-third of cases. These recurrences can be central or peripheral and surgery if possible is the mainstay of treatment. The pelvic reirradiation must not be the first choice for such patients with recurrent pelvic tumors after a previous course of irradiation. As minimal data are available on the toxicity of additional radiation therapy, this approach would be considered only when there is no other alternative for effective therapy and in the face of progressive and severe symptom.[21],[22] Preexisting late rectal or bladder toxicity is a strong deterrent for consideration of reirradiation. Cumulative dose to several organs at risk such as femoral heads, bone marrow, small bowel, urethra, vagina, and sigmoid should also be considered. As far as technique is concerned, preference should be given to intraoperative RT or brachytherapy. Combining surgery with postoperative RT gives best results. For central pelvic recurrences, interstitial brachytherapy is the preferred modality with the aim of achieving the reirradiation EQD2 of 35–45 Gy in 5–7#. For nodal recurrences, stereotactic body RT obviously holds edge and an reirradiation EQD2 of 24–30 Gy in 3/5 fractions should be attempted [Table 4].[24]


  Bone and Brain Metastases Top


Reirradiation for painful bone metastases is considered when there is no pain relief after first-time radiation or there is partial response to first-time radiation and those in whom a better response is desired and in cases of pain relapse after either partial or complete response to the first time radiation. The ideal approach toward reirradiation will involve proper evaluation of the pain, evaluation for associated fracture, soft-tissue component, and weight bearing.[25],[26] Dose and fractionation of the initial radiation is important as retreatment after a single fraction (4, 6, or 8 Gy) treatment is quite feasible and tolerable.[27] Furthermore, the response to the initial radiation and pain relief provided needs to be considered since there is little evidence that the initial nonresponders will benefit from reirradiation. For most patients, a single treatment with 8 Gy is noninferior to treatment with 20 Gy in 5 fractions or other protracted courses.[27],[28]

The role of whole-brain radiation therapy (WBRT), surgical excision, stereotactic radiosurgery (SRS), and chemotherapy for patients with newly diagnosed brain metastases is well known, but limited salvage options exist for patients with multiple recurrent brain metastases treated previously with WBRT or SRS-stereotactic RT (SRT).[29],[30] For those individuals who survive long enough to experience recurrence/progression of previously treated brain metastases treatment of recurrent/progressive brain metastases be individualized based on functional status, extent of disease, volume/number of metastases, recurrence or progression at original versus nonoriginal site, previous treatment, and type of primary cancer.[31],[32] The most important consideration before reirradiation is the expected survival of the patient and performance status and the pretreatment neurological status. For isolated recurrences in patients initially treated with WBRT or SRT, with good performance status, surgical option should always be sought.[33] Systemic therapy and chemotherapy options for widespread recurrences should also be kept in mind.[34],[35],[36],[37],[38]


  Conclusion Top


Reirradiation for selected locoregional recurrences and second primary cancers is feasible option when surgery is difficult and mutilating. Proper selection of cases is the main factors deciding favorable outcome. Apart from the interval and the initial radiation dose–volume issues that should be kept in mind before contemplating a course of reirradiation are the performance status of the patient, expected survival, and the organ at least damage caused by the initial radiation treatment. Dose memory and threshold time gap is not established conclusively and are areas of research for most sites. Finally, a balance has to be maintained between the perceived gain and the potential harm caused by such a course.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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  [Table 1], [Table 2], [Table 3], [Table 4]



 

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