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Head and Neck Cancer |
a Department of Plastic Surgery, Canniesburn Hospital, Glasgow Royal Infirmary, Glasgow, United Kingdom; b Department of Otolaryngology/Head and Neck Surgery, VU University Medical Center, Amsterdam, The Netherlands; c Department of Plastic Surgery, Christie Hospital, Manchester, United Kingdom
Key Words. Head and neck cancer • RADPLAT • Targeted chemoradiation • Intra-arterial chemotherapy
Correspondence: Gary L. Ross, M.D., Department of Plastic Surgery, Christie Hospital, Southmoor Road, Manchester, United Kingdom. Telephone: 44-161-286-6534; Fax: 44-161-291-6381; e-mail: gary.ross{at}canniesburn.org
Received September 19, 2005; accepted for publication March 4, 2006.
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ABSTRACT |
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 Top Abstract Evolution of Treatment for...TechniqueStudy OutcomesControl of Nodal DiseaseRADPLAT in Other CentersToxicityPredictors of SuccessOrgan Preservation and Quality...Detection of Recurrence after...Surgery After Chemoradiation...Further Applications of the...ConclusionsDisclosure of Potential...References |
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EVOLUTION OF TREATMENT FOR ADVANCED HEAD AND NECK CANCER |
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TopAbstractEvolution of Treatment for...TechniqueStudy OutcomesControl of Nodal DiseaseRADPLAT in Other CentersToxicityPredictors of SuccessOrgan Preservation and Quality...Detection of Recurrence after...Surgery After Chemoradiation...Further Applications of the...ConclusionsDisclosure of Potential...References |
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Chemotherapeutic agents, particularly cisplatin, have been shown to achieve high tumor response rates in the head and neck [5, 6] that have been shown to be dose related [7, 8]. However, cisplatin’s side effects, particularly nephrotoxicity, limit the useable dose in humans. Despite these promising initial results, chemotherapy has not been shown to improve survival when used alone or in the adjuvant/neoadjuvant setting for advanced head and neck cancer [9, 10], aside from one recent postoperative randomized trial targeting high-risk disease [11]. In addition, in a large prospective study of 332 patients with stage III or IV laryngeal cancer, induction chemotherapy followed by radiotherapy showed no difference in survival compared with laryngectomy and radiation therapy (p = .98) [12]. This suggests that an organ-preserving approach may be used without adversely affecting survival.
Potentiation of the cytotoxic effects of radiation occurs when chemotherapy is administered concurrently, a process termed radiosensitization. This effect, first noted in murine tumors [13], has demonstrated mixed tumor response rates with current chemoradiation protocols for head and neck cancer, in the range of 47%–84% [14–19]; a clear survival benefit over conventional treatment with surgery and postoperative radiotherapy has not been demonstrated in randomized trials [2, 12]. Concurrent chemoradiation appears to offer greater benefit than sequential treatment. In two recent phase III trials, chemoradiation demonstrated higher locoregional control rates than with radiotherapy alone in the postoperative setting [4, 20]. However, improvements in disease-free and overall survival times were observed in only one of these studies.
Acquired tumor resistance to cisplatin has been shown to occur after as few as two to four cycles [21, 22] and may explain in part the failure of chemotherapy to improve survival. It was previously demonstrated in vitro [7] and in vivo [8] that resistance may be overcome through the use of higher concentrations of cisplatin. However, in human subjects, the higher concentrations required could lead to devastating systemic toxicity—already a major problem with chemoradiation protocols, which also appear to aggravate radiation-induced mucositis [23]. Treatment delays and dose reductions are commonly reported in chemoradiation protocols, adversely affecting locoregional tumor control rates and overall survival.
The undesirable systemic side effects of i.v. chemotherapy can be partially circumvented through the use of regional chemotherapy techniques to deliver higher doses of chemotherapeutic agents directly into the tumor bed, allowing first-pass metabolism of the drug by the tumor. Head and neck cancers, which metastasize to distant sites infrequently, appear well suited to this approach.
Early attempts at intralesional injection of chemotherapy were largely unsuccessful because of problems with poor diffusion of the drug into tumor tissue, which led to the addition of adrenaline to improve local penetration. Initial reports are encouraging, with a reported 50% response rate and no dose-limiting toxicity in a series of 82 patients [20]. Another approach to improve the penetration of intra-lesionally injected chemotherapy is the use of electroporation therapy. Promising results have been reported in a series of 12 patients with oral cancer, of whom 10 patients had a complete response (CR) [24].
Intra-arterial infusion of chemotherapeutic agents was first carried out in the 1960s [25, 26]; however, technical difficulties and poor initial results prevented the technique from gaining popularity until the 1980s, when Lee et al. [27] reported a 91% tumor response rate in 24 patients treated with combined intra-arterial cisplatin and i.v. chemotherapy for advanced paranasal sinus carcinoma. Importantly, eight patients avoided craniofacial surgery as a result of their excellent response to treatment.
Several authors subsequently reported on the use of intra-arterial chemotherapy alone, but CR rates remained disappointingly low, in the range of 7.7%–33% [27–31]. The main criticism leveled at regional chemotherapy techniques was that there was no clear survival benefit over conventional systemic chemotherapy but a considerably greater risk of local toxicity. In addition, systemic distribution of cisplatin distal to the tumor site meant that systemic toxicity remained a considerable problem [32].
To address these problems, the RADPLAT protocol was developed at the University of California at San Diego and the University of Tennessee, Memphis. This technique involves four cycles of targeted intra-arterial cisplatin infusion with concurrent radiation therapy. Simultaneous with each intra-arterial infusion, the neutralizing agent sodium thiosulphate is infused into the systemic circulation and binds covalently with cisplatin to form a soluble, nontoxic compound [33]. This "neutralization" of cisplatin effectively increases the drug’s plasma clearance, allowing very high doses to be administered directly into the tumor tissue while minimizing systemic toxicity. Using the RADPLAT procedure, dose intensities up to 10 times those used in standard chemotherapy protocols may be administered [7, 8].
The goal of intra-arterial infusion during RADPLAT is to target the portion of tumor considered to be bulky or infiltrative and likely to fail treatment with radiation therapy alone [34].
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TECHNIQUE |
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Four cycles of targeted chemotherapy are administered on days 1, 8, 15, and 22, with radiotherapy commencing on day 1 and continuing for 5 days using opposed tangential fields and fractions of 2.0 Gy per day to a total planned radiation dose of 70–74 Gy, dependent on disease stage. Radiation to the neck is dependent on clinical involvement, with uninvolved necks treated to 50 Gy while positive necks are boosted with electrons to 60–66 Gy.
Planned neck dissection was initially carried out in all patients with bulky nodal disease (nodal [N] stage 2 or 3), regardless of response to RADPLAT. However, this policy was subsequently changed to salvage neck dissection when it became clear that clinical complete responders were also negative at pathologic evaluation of neck dissection specimens [36].
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STUDY OUTCOMES |
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The RADPLAT protocol has since been shown to achieve impressive CR and PR rates and locoregional control (Table 1
) while maintaining a favorable side-effect profile. Following on from their initial work, Robbins et al. [38] evaluated the response to treatment in 29 patients with previously untreated stage IV disease and observed complete pathologic responses in 23/24 evaluated patients (96%). Grade III or IV chemotoxicities occurred after only 14 of the 110 infusions carried out during the study (12.7%). At a median follow-up of 22 months, the projected 3-year overall and disease-free survival rates were 88% and 53%, respectively. Further studies from this group subsequently confirmed these promising response and survival rates, and extended the application of RADPLAT from patients with functionally inoperable disease only to an organ-preserving approach in patients with technically resectable disease [39, 40].
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The reported CR rates following RADPLAT treatment appear to compare favorably with those observed in randomized trials of i.v. chemoradiation protocols [15, 41, 42]. In addition, the pattern of recurrence seen following RADPLAT treatment is unusual compared with previous head and neck cancer studies, in which locoregional failure predominates as the mode of death. It is likely that better local and regional control effectively unmask previously occult distant metastases, and this may require the addition of a systemic component to treatment in future studies using the RADPLAT protocol.
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CONTROL OF NODAL DISEASE |
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In a further study of 31 patients with stage N3 disease, Ahmed et al. [44] described survival and local and regional control rates following RADPLAT treatment. Nodal disease responded to treatment in 25 of 26 evaluated patients (96%). However, 21 of these (81%) were PRs, and most patients in the study (n = 19) went on to have salvage neck dissection at the time of restaging. Of the 23 patients rendered disease free, there was only one recurrence at the primary site and none in the neck at a median follow-up of 15 months. Distant metastases occurred in 11 patients (48%). The authors reported a projected 3-year overall survival rate of 41%, a disease-specific survival rate of 43%, and a locoregional survival rate of 67%.
The reported regional response and 3-year locoregional control rates suggest that the effects of targeted intra-arterial chemoradiation are not strictly confined to the local area infused, and it has been suggested that incomplete systemic neutralization of cisplatin by sodium thiosulphate may allow sufficient amounts to remain in the circulation and act as a radiosensitizing agent [40].
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RADPLAT IN OTHER CENTERS |
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Feasibility, or the ability to deliver the full prescribed dose of both cisplatin and radiotherapy, was examined recently in the multicenter setting in a prospective phase II trial [46]. Eleven institutions participated, eight of whom were inexperienced in the delivery of RADPLAT. Sixty-seven patients were enrolled, of whom 61 were evaluated. RADPLAT was shown to be feasible at all sites, with 100% of patients at experienced centers completing the protocol. This number was only 83% at inexperienced centers, which was nevertheless above the 80% feasibility cutoff. Eighty-five percent of patients demonstrated a CR at the primary site, and 88% had a CR in the neck (80% overall). The 1- and 2-year overall survival rates were projected at 72% and 63%, with disease-free survival rates of 62% and 46%, respectively. Severe (grade III, IV, and V) toxicities were seen in 44%, 39%, and 3% or patients, respectively. However, there were significant differences in the rates of grade IV and V toxicity between experienced and inexperienced centers (grade IV, 14% vs. 47%; grade V, 0% vs. 4%; no p value given), and this held true for both hematologic and nonhematologic toxicities. The authors stated that developing toxicities may have been recognized earlier at the experienced centers, allowing for treatment to be temporarily halted. Failure to recognize developing toxic reactions at an early stage could account for the higher rate of severe toxicities observed at the inexperienced centers.
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TOXICITY |
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Initial experience with RADPLAT suggests that mucosal toxicity rates may be less than those observed in conventional chemoradiation protocols. In Robbins et al.’s [40] phase II trial of 60 patients with stage III/IV disease, grade III mucositis was encountered in only 12 patients (20%). It has been suggested that sodium thiosulphate may exert a radioprotective effect; the mechanism of this is not exactly known but may occur through scavenging of free radicals by the thiol compound.
Systemic neutralization of cisplatin by sodium thiosulphate diminishes the risk of systemic toxicity, potentially allowing a greater proportion of patients to complete the full course of treatment. Robbins et al. [40] reported that 90% of patients received all four cycles of chemotherapy, whereas 85% completed the full RADPLAT protocol. The grade III toxicities observed in that trial were hematologic (n = 6), gastrointestinal (n = 6), vascular (n = 4), neurological (n = 4), and mucosal, secondary to radiotherapy (n = 12; 20%). Most notable was the significant absence of grade IV–V nonhematologic toxicities in this group of 60 patients (only two grade IV gastrointestinal toxicities), unlike what is typically reported in virtually all chemoradiation trials. The absence of nephrotoxic events is attributed to the fact that sodium thiosulphate is extensively concentrated in the urine, providing additional protection to the kidneys.
The mild-to-moderate chemotoxic effects observed in some patients support the suggestion that small amounts of cisplatin may escape systemic neutralization by sodium thoisulphate, thereby entering the systemic circulation [40].
Chemotoxicity rates following RADPLAT appear to compare favorably with those of i.v. chemotherapy protocols, with reported overall incidences as low as 5.5% [39]. Gemmete [48] conducted a retrospective review of 105 patients undergoing 385 RADPLAT cycles and reported 41 grade III/IV chemotoxic events (10.6%). Of these, 29 were mucosal, nine were hematologic (two neutropenic sepsis), two were otologic, and one was gastrointestinal. These results were mirrored in a large prospective study of 213 patients [36], in which only 21 patients (10%) received less than three infusions as a result of problems with toxicity. One hundred thirty of 213 patients (61%) did not experience any grade III or IV reactions, and six treatment-related deaths were encountered (2.8%). This compares favorably with the 5%–18% mortality rate reported in other head and neck cancer chemoradiation trials [49, 50].
Complications related to the intra-arterial infusion technique may also arise, as reported by Gemmete [48]. Repeated catheterization may lead to groin-site complications, and two patients in this series (2%) required femoro-femoral bypass surgery secondary to external iliac artery occlusion. Vascular complications were observed in 25 patients (6.5%), while six patients (1.6%) experienced transient ischemic attacks (n = 3) or cerebrovascular accidents (n = 3). These rates are comparable with those reported following diagnostic angiographic procedures.
Ototoxicity is a well-documented complication of i.v. cisplatin-based chemotherapy, with reported rates as high as 81% [51]. In a prospective series of 70 patients treated with RADPLAT, Madasu et al. [52] demonstrated that the incidence of hearing loss is related to the cumulative cisplatin dose (ranging from 25% at 150 mg/m2 to 60% at 600 mg/m2). However, the observed hearing loss was generally minimal (10–20 dB) and confined to frequencies greater than 2–3 kHz.
On the whole, morbidity following the RADPLAT procedure appears to be relatively low, comparing favorably with the existing literature for "conventional" chemoradiation protocols. However, the clinician should be aware of the potential for additional complications related to the technical aspects of intra-arterial cisplatin delivery, and the apparent learning curve for institutions new to the procedure.
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PREDICTORS OF SUCCESS |
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TopAbstractEvolution of Treatment for...TechniqueStudy OutcomesControl of Nodal DiseaseRADPLAT in Other CentersToxicityPredictors of SuccessOrgan Preservation and Quality...Detection of Recurrence after...Surgery After Chemoradiation...Further Applications of the...ConclusionsDisclosure of Potential...References |
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Robbins et al. [53] addressed this issue in their prospective series of 240 patients treated with RADPLAT for stage III or IV disease. At a median follow-up of 58 months, the authors reported an excellent 5-year local control rate (210/240, 83%). Factors found to significantly influence this outcome included the total dose of radiotherapy, number of nodal levels involved, and persistence of nodal disease after treatment. Tumor (T)-stage classification was found to be a significant predictor of local control only when stage T2 tumors were included in the analysis. No difference was seen between the stage T3 and T4 groups (p = .089), indicating that T stage may not be the optimal means of risk stratification for this patient group.
In a smaller study of 64 patients, primary tumor volume greater than 19.6 mm3 was strongly associated with a higher local recurrence rate (94% vs. 57%; p = .001) and lower 5-year survival rate (14.1% vs. 41.5%; p = .018) [54]. The authors postulated that this may be related to the poorly vascularized areas of central necrosis frequently seen in large tumors, preventing effective intra-arterial delivery of chemotherapy [55].
The reported improvements in locoregional control rates have been partially offset by the unmasking of distant metastases in a significant proportion of patients undergoing treatment with RADPLAT [36]. It is therefore of paramount importance to recognize and address significant risk factors for distant failure in order that the choice of treatment may be tailored appropriately.
In a large prospective series, Doweck et al. [56] reported recurrence of disease in 84 of 250 patients treated with the RADPLAT protocol (33.6%). Of these, 45 (18%) had distant metastases and 39 (15.6%) had locoregional metastasis. Reported risk factors for distant metastasis included N stage (p = .02), primary tumor in the hypopharynx (p = .01), lower neck involvement (p = .002), number of neck levels involved (p = .001), and bilateral nodal disease (p = .02). Similar results were described by van den Broek et al. [57] in a series of 92 patients, with tumor volume (p = .003), lowest involved neck level (p = .007), pretreatment weight loss >10% (p = .02), and associated comorbidity (p = .01) all found to significantly influence survival following RADPLAT treatment.
Based on these results, variables such as age and T-stage classification appear to be of secondary importance to tumor volume and nodal status. It is apparent that the variables influencing local and distant control, and therefore survival, following RADPLAT treatment may differ considerably from those known to affect outcomes following conventional treatment. Specific biologic markers of response to chemoradiation may be helpful in predicting outcomes of RADPLAT. Studies to analyze the predictive value of different markers are ongoing.
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ORGAN PRESERVATION AND QUALITY OF LIFE FOLLOWING RADPLAT |
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Robbins et al. [39] first described RADPLAT as an alternative to major resection in a series of 42 patients with advanced laryngeal and pharyngeal cancer and reported a CR in 36 patients (86%). Only five recurrences were observed at a median follow-up of 13 months, and the 2-year locoregional control rate was estimated at 86%. Overall and disease-specific survival rates at 2 years were 64% and 76%, respectively. Importantly, 28 of 31 surviving patients (90%) retained their larynx, 27 (87%) maintained oral food intake, and all the surviving patients were able to speak.
The preservation of organs does not necessarily ensure preservation of organ function, and problems with swallowing, speech, and breathing may also occur following nonsurgical treatment [58]. Staton et al. [59] conducted a retrospective chart review of 45 patients with stage III–IV laryngeal carcinoma enrolled into a RADPLAT protocol study in order to determine predictors of functional outcome following larynx-preserving RADPLAT treatment. At 6 months post-treatment, 10 patients (22%) required tracheostomy and gastrostomy, three patients required tracheostomy alone (6.7%), and three patients required gastrostomy alone (6.7%). Poor functional outcome was positively predicted by the presence of vocal cord fixation by the tumor at initial presentation (p = .0065), while stage T4 status and massive cartilage invasion showed strong trends toward association (p = .149 and p = .14, respectively). Age, tumor site, comorbid chronic obstructive pulmonary disease, neck dissection, and nodal status were not found to affect functional outcomes. The authors concluded that the ability to predict a poor functional outcome of organ-preserving RADPLAT treatment can assist in the selection of treatment modality for patients in this population.
Newman et al. [60] assessed the ability to eat normally in a series of 47 patients treated with RADPLAT for advanced head and neck cancer and found that swallowing ability was markedly improved (72% reported normal swallowing post-treatment, compared with 38% pretreatment). At 18 months of follow-up, percutaneous endoscopic gastrostomy (PEG) tubes were required in six patients (13%), compared with four patients (9%) pretreatment. A mean weight loss of 10% body weight was observed on initiation of treatment, after which weight remained stable. This trend has been previously noted in patients undergoing radiotherapy alone [61].
In a further study carried out by the same group, Murry et al. [62] used patient questionnaires to determine that both swallowing ability and QoL were diminished prior to RADPLAT treatment for advanced cancer and decreased further during the treatment cycle (p < .05). However, QoL subsequently improved and exceeded the pretreatment level at 6 months after completion of treatment.
Similar results were reported in a series of 26 patients with stage IV disease by Ackerstaff et al. [63], with a decline in QoL observed at 6 weeks post-treatment and a subsequent improvement to exceed pretreatment values in terms of functional ability and head and neck symptoms (p < .001). At a 12-month follow-up, 16 of 26 patients (62%) reported little or no problems with mastication, while 19 patients (73%) had no problems with swallowing. Five patients (19%) required PEG tube feeding at 1 year. Twenty-three patients described their voice as normal (n = 16; 61%) or somewhat normal (n = 7; 27%), whereas only three patients (12%) reported severe voice-related problems. The most frequently reported problem post-treatment was xerostomia, with all patients experiencing a decrease in volume or thicker consistency of saliva.
The results of these studies indicate that RADPLAT is associated with high rates of function preservation and improved QoL in patients with advanced cancer of the head and neck.
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DETECTION OF RECURRENCE AFTER CHEMORADIATION |
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SURGERY AFTER CHEMORADIATION TREATMENT |
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Postoperative complications after en bloc salvage surgery for head and neck cancer occur in more than half of the patients, and one third of these patients experiences major complications [66, 67]. In a retrospective study at Memorial Sloan-Kettering Cancer Center, postoperative complications were compared among patients undergoing primary total laryngectomy, salvage laryngectomy after radiotherapy, or salvage laryngectomy after chemoradiation. Chemoradiation was found to be an independent predictor of local complications and pharyngocutaneous fistula [68].
Two thirds of patients with local and/or regional recurrence after larynx preservation with chemoradiation are candidates for salvage surgery. Moreover, negative surgical margins appear to be more difficult to obtain during salvage laryngectomy than during primary laryngectomy [69]. Although this is in part related to the selection of more aggressive tumors, it is likely that difficulties in macroscopic differentiation between recurrent tumor and post-chemoradiation changes during surgery also play a role.
The decision to perform a neck dissection following chemoradiation is clear when patients have proven residual neck disease. However, distinguishing between residual metastasis and chemoradiation sequelae is difficult in most cases with a residual neck mass because post-treatment induration and fibrosis obscure accurate clinical assessment. Therefore, in some institutes, routine planned neck dissections have been performed because no reliable clinical parameters are available to predict pathological status after chemoradiation [70, 71].
Performing a neck dissection after chemoradiation runs the risk of wound-healing problems; pedicled pectoralis major muscle flaps may be used if wound healing problems are anticipated, at the expense of greater morbidity. Complication rates of 26%–35% have been reported for planned neck dissection after chemoradiation [70]. Some centers perform selective neck dissection or lumpectomy instead of radical neck dissection to minimize the surgical wound bed and consequently the risk for wound-healing problems [71].
Viable tumor cells are found in only 30%–50% of neck dissection specimens [43, 45]. Moreover, controversy surrounds the use of planned neck dissection in patients with a CR to chemoradiation because the vast majority of these patients have negative neck dissection specimens on histopathological examination [70]. The difficulty in evaluating for recurrence has made salvage neck surgery less effective, and late recurrences in the neck are rarely surgically salvageable [72].
Because salvage treatment after chemoradiation has a questionable prognosis and a high incidence of complications, RADPLAT may not be the choice of treatment in all patients with advanced-stage disease. A reliable pretreatment probability model for predicting outcome after RADPLAT is needed to select patients with resectable tumors who are likely to benefit from chemoradiation. If RADPLAT is unlikely to cure patients with resectable tumors, these patients should instead be treated with primary surgery [57].
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FURTHER APPLICATIONS OF THE RADPLAT TREATMENT PROTOCOL |
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TopAbstractEvolution of Treatment for...TechniqueStudy OutcomesControl of Nodal DiseaseRADPLAT in Other CentersToxicityPredictors of SuccessOrgan Preservation and Quality...Detection of Recurrence after...Surgery After Chemoradiation...Further Applications of the...ConclusionsDisclosure of Potential...References |
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Samant et al. [73] described the use of RADPLAT in a series of 135 patients with stage T4 disease, 45 of whom had evidence of bone or cartilage invasion. The authors noted that the CR rate did not differ significantly between patients with or without invasion (66.7% vs. 71.1%; p = .71), and the same was true for the 2-year overall survival rate (46.3% vs. 36.9%; p = .36). They concluded that the RADPLAT protocol can be used as a viable treatment option in patients with advanced head and neck cancer invading bone or cartilage, a patient group for whom organ preservation approaches have traditionally been contraindicated.
Neo-RADPLAT is the acronym given to the use of targeted intra-arterial chemoradiation cytoreduction prior to surgery, as recently described by Robbins et al. [74] in a series of 25 patients with stage T2 or T3 oro/oropharyngeal tumors. A CR was demonstrated at the primary site in 20 patients (80%) and at the neck in 10 patients (79%). PRs were observed in all remaining patients. Fourteen patients subsequently underwent tumor nidusectomy, five of whom had involved margins and required conventional resection. Nine patients (11 neck sides) also had a selective neck dissection because of clinical evidence of residual nodal disease, three of whom were found to be positive. At a median follow-up of 56 months, the estimated 5-year overall survival, disease-specific survival, and locoregional control rates were 54%, 64%, and 74%, respectively. Recurrences were observed in five patients, all of which occurred at the primary site. The authors found that the use of triple-modality therapy was feasible and efficacious in patients with stage T2–T4 oro/oropharyngeal carcinoma, and that presurgical cytoreduction reduced the extent of resection, allowing greater preservation of function. In addition, the total radiation dose in that study was reduced to 50 Gy (10 Gy/week) without adversely affecting response rate. The authors suggested that the maximum radiation dose may not be required in the context of multimodality treatment, and further study of this is required.
A similar triple-therapy approach was described by Madison et al. [75] in the treatment of 11 patients with advanced sinonasal malignancy. The authors reported that the presurgical reduction in size achievable with targeted chemoradiation allows for surgical management of otherwise unresectable tumors, and improvements in local control and survival with a low complication rate are achievable with this approach.
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CONCLUSIONS |
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TopAbstractEvolution of Treatment for...TechniqueStudy OutcomesControl of Nodal DiseaseRADPLAT in Other CentersToxicityPredictors of SuccessOrgan Preservation and Quality...Detection of Recurrence after...Surgery After Chemoradiation...Further Applications of the...ConclusionsDisclosure of Potential...References |
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RADPLAT may also be of benefit in the treatment of selected patients with resectable disease, with preservation of swallowing and speech following RADPLAT treatment demonstrating significant improvements in terms of patient QoL. However, careful patient selection is required in order to minimize the problems associated with salvage surgery after chemoradiation.
Future refinements to the RADPLAT protocol may involve altered radiation fractionation [76] or the addition of a systemic therapy component in order to target occult distant metastases [40]. Current phase II data are encouraging, and new applications for RADPLAT continue to emerge. However, phase III randomized controlled trials are required in order to directly compare RADPLAT with i.v. chemoradiation therapy, the current standard of care [46, 77]. The first results of such a trial in The Netherlands are expected at the end of this year. It can be concluded that RADPLAT is a viable alternative to surgery, but careful selection of suitable patients is of utmost importance.
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DISCLOSURE OF POTENTIAL CONFLICTS OF INTEREST |
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REFERENCES |
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