Niloy Ranjan Datta

Head and neck cancers: results of thermoradiotherapy versus radiotherapy

Sixty-five patients were included in a randomized clinical study to evaluate the efficacy of local hyperthermia as a concomitant agent to radiotherapy in the treatment of carcinoma of the head and neck region. Local hyperthermia at 42-43 degrees C was generated by a 27 x 12 MHz radiofrequency diathermy unit and was used before radiotherapy in 33 patients; the remaining 32 patients were subjected to radiotherapy alone. The response in patients with early lesions (Stage I and II) was similar for both the groups, while in patients with advanced disease (Stage III and IV) a significantly better tumour control was obtained by the use of the combined treatment.

Local hyperthermia combined with radiotherapy and-/or chemotherapy: Recent advances and promises for the future

Hyperthermia, one of the oldest forms of cancer treatment involves selective heating of tumor tissues to temperatures ranging between 39 and 45°C. Recent developments based on the thermoradiobiological rationale of hyperthermia indicate it to be a potent radio- and chemosensitizer. This has been further corroborated through positive clinical outcomes in various tumor sites using thermoradiotherapy or thermoradiochemotherapy approaches. Moreover, being devoid of any additional significant toxicity, hyperthermia has been safely used with low or moderate doses of reirradiation for retreatment of previously treated and recurrent tumors, resulting in significant tumor regression. Recent in vitro and in vivo studies also indicate a unique immunomodulating prospect of hyperthermia, especially when combined with radiotherapy. In addition, the technological advances over the last decade both in hardware and software have led to potent and even safer loco-regional hyperthermia treatment delivery, thermal treatment planning, thermal dose monitoring through noninvasive thermometry and online adaptive temperature modulation. The review summarizes the outcomes from various clinical studies (both randomized and nonrandomized) where hyperthermia is used as a thermal sensitizer of radiotherapy and-/or chemotherapy in various solid tumors and presents an overview of the progresses in loco-regional hyperthermia. These recent developments, supported by positive clinical outcomes should merit hyperthermia to be incorporated in the therapeutic armamentarium as a safe and an effective addendum to the existing oncological treatment modalities.

Radiation Therapy Infrastructure and Human Resources in Low- and Middle-Income Countries: Present Status and Projections for 2020

PURPOSE Radiation therapy, a key component of cancer management, is required in more than half of new cancer patients, particularly in low- and middle-income countries (LMICs). The projected rise in cancer incidence over the next decades in LMICs will result in an increasing demand for radiation therapy services. Considering the present cancer incidence and that projected for 2020 (as listed in GLOBOCAN), we evaluated the current and anticipated needs for radiation therapy infrastructure and staffing by 2020 for each of the LMICs. METHODS AND MATERIALS Based on World Bank classification, 139 countries fall in the category of LMICs. Details of teletherapy, radiation oncologists, medical physicists, and radiation therapy technologists were available for 84 LMICs from the International Atomic Energy Agency-Directory of Radiotherapy Centres (IAEA-DIRAC) database. Present requirements and those for 2020 were estimated according to recommendations from the IAEA and European Society for Radiotherapy & Oncology (ESTRO-QUARTS). RESULTS Only 4 of the 139 LMICs have the requisite number of teletherapy units, and 55 (39.5%) have no radiation therapy facilities at present. Patient access to radiation therapy in the remaining 80 LMICs ranges from 2.3% to 98.8% (median: 36.7%). By 2020, these 84 LMICs would additionally need 9169 teletherapy units, 12,149 radiation oncologists, 9915 medical physicists, and 29,140 radiation therapy technologists. Moreover, de novo radiation therapy facilities would have to be considered for those with no services. CONCLUSIONS Twelve pragmatic steps are proposed for consideration at national and international levels to narrow the gap in radiation therapy access. Multipronged and coordinated action from all national and international stakeholders is required to develop realistic strategies to curb this impending global crisis.

Variations of intracavitary applicator geometry during multiple HDR brachytherapy insertions in carcinoma cervix and its influence on reporting as per ICRU report 38

PURPOSE This paper examines the extent of variation in the applicator geometry during multiple high dose rate (HDR) intracavitary brachytherapy (ICBT) applications and its impact on reporting as per ICRU report 38. MATERIALS AND METHODS Eighty orthogonal radiographs from 20 consecutive patients of carcinoma cervix (FIGO stages, IIA-IIIB) having four HDR ICBT applications of 6 Gy each at weekly intervals following teletherapy were evaluated. The applicator consisted of a flexible intrauterine tandem (IUT) independent of the ovoid assembly. The applicator geometry was evaluated in terms of: alpha angle, beta angle, intrauterine length (IUTL), interovoid (IOV), os to right ovoid (ORT) and os to left ovoid (OLT) distances along with vertical (VDL) and anteroposterior displacements (ADL) of the os with respect to the ovoids. The Cartesian co-ordinates (X, Y, and Z) of the IUT tip, centre of both ovoids and os were also measured. Doses to right point A (ARD), left point A (ALD), along with a reference volume of 6 Gy for ICRU height (IRH), width (IRW), thickness (IRT) and volume (IRV) were estimated for each application. RESULTS Highly significant differences (P<0.001) between four insertions in any given patient across 20 patients for alpha angle, beta angle, IUTL, IOV, ORT, VDL, co-ordinates of the IUT, ovoids and os were observed, except for ADL (P=0.041) and OLT (P=0.247). As a consequence, variations were observed in ARD (P=0.027), ALD (P=0.017); IRH, IRW, IRT and IRV (all P<0.001). Applicator factors which influenced the various dose specification parameters were: beta angle and ORT for both ARD and ALD; UTLN, VDL and ORT for IRH; UTLN and IOV for IRW; UTLN for IRT and VDL for the 6 Gy IRV. CONCLUSIONS A significant variation of the applicator geometry and its movement was observed in patients undergoing multiple HDR ICBT. This could have implications for reporting dose and volume specifications as required by ICRU report 38.

Hyperthermia and Radiation Therapy in Locoregional Recurrent Breast Cancers: A Systematic Review and Meta-analysis.

PURPOSE To conduct a systematic review and meta-analysis to evaluate the outcome of hyperthermia (HT) and radiation therapy (RT) in locally recurrent breast cancers (LRBCs). METHODS AND MATERIALS A total of 708 abstracts were screened from 8 databases according to the PRISMA guidelines. Single-arm and 2-arm studies, treating LRBCs with HT and RT but without surgery (for local recurrence) or concurrent chemotherapy were considered. The evaluated endpoint was complete response (CR). RESULTS Thirty-one full text articles, pertaining to 34 studies, were shortlisted for the meta-analysis. Eight were 2-arm (randomized, n=5; nonrandomized, n=3), whereas 26 were single-arm studies. In all, 627 patients were enrolled in 2-arm and 1483 in single-arm studies. Patients were treated with a median of 7 HT sessions, and an average temperature of 42.5°C was attained. Mean RT dose was 38.2 Gy (range, 26-60 Gy). Hyperthermia was most frequently applied after RT. In the 2-arm studies, a CR of 60.2% was achieved with RT + HT versus 38.1% with RT alone (odds ratio 2.64, 95% confidence interval [CI] 1.66-4.18, P<.0001). Risk ratio and risk difference were 1.57 (95% CI 1.25-1.96, P<.0001) and 0.22 (95% CI 0.11-0.33, P<.0001), respectively. In 26 single-arm studies, RT + HT attained a CR of 63.4% (event rate 0.62, 95% CI 0.57-0.66). Moreover, 779 patients had been previously irradiated (696 from single-arm and 83 from 2-arm studies). A CR of 66.6% (event rate 0.64, 95% CI 0.58-0.70) was achieved with HT and reirradiation (mean ± SD dose: 36.7 ± 7.7 Gy). Mean acute and late grade 3/4 toxicities with RT + HT were 14.4% and 5.2%, respectively. CONCLUSIONS Thermoradiation therapy enhances the likelihood of CR rates in LRBCs over RT alone by 22% with minimal acute and late morbidities. For even those previously irradiated, reirradiation with HT provides locoregional control in two-thirds of the patients. Thermoradiation therapy could therefore be considered as an effective and safe palliative treatment option for LRBCs.

Anaphylaxis to cisplatin following nine previous uncomplicated cycles

Abstract. Anaphylaxis to cisplatin is an infrequent life-threatening complication which may occur even in patients who have received prior treatment with cisplatin. We report here a patient with carcinoma of the cervix with recurrent abdominal and thoracic disease who was previously treated with concurrent cisplatin and radiation for local control of pelvic disease. After nine previous uncomplicated cycles she developed severe anaphylaxis to cisplatin. The anaphylactic reaction was managed successfully with corticosteroids, nebulization with β2 agonists, and isotonic fluid support. With the extensive use of platinum-based chemotherapy regimens, either alone or in combination with radiation therapy in the management of gynecological malignancies, this uncommon complication should be kept in mind for early detection and successful management.

Improvement of radiotherapy facilities in developing countries: a three-tier system with a teleradiotherapy network

Incidence of cancer has been projected to rise worldwide by around 50% in the next 20 years, most of which will be in developing countries. To face this unprecedented global health problem, it is essential to plan effective health-care strategies. Radiotherapy-a main component of the multidisciplinary therapeutic approach for cancer-involves a huge capital investment that can pose difficulties for developing countries. Limited resources should therefore be used effectively to meet the projected requirements and to find ways to offer quality-assured radiotherapy to patients. Taking advantage of the global explosion of telecommunication technology, we present a proposal for creation of an integrated three-tier radiotherapy service, which consists of primary, secondary, and tertiary radiotherapy centres in developing countries-coordinated through a teleradiotherapy network. Such a network could be cost effective, help to bridge the gap, and give all patients access to the state-of-the-art technology in radiotherapy.

Hyperthermia and radiotherapy in the management of head and neck cancers: A systematic review and meta-analysis

Abstract Purpose: A systematic review and meta-analysis was conducted to evaluate the outcome of controlled clinical trials in head and neck cancers (HNCs) using hyperthermia and radiotherapy versus radiotherapy alone. Material and methods: A total of 498 abstracts were screened from four databases and hand searched as per the PRISMA guidelines. Only two-arm studies treating HNCs with either radiotherapy alone, or hyperthermia and radiotherapy without concurrent chemotherapy or surgery were considered. The evaluated end point was complete response (CR). Results: Following a detailed screening of the titles, abstracts and full text papers, six articles fulfilling the above eligibility criteria were considered. In total 451 clinical cases from six studies were included in the meta-analysis. Five of six trials were randomised. The overall CR with radiotherapy alone was 39.6% (92/232) and varied between 31.3% and 46.9% across the six trials. With thermoradiotherapy, the overall CR reported was 62.5% (137/219), (range 33.9–83.3%). The odds ratio was 2.92 (95% CI: 1.58–5.42, p = 0.001); the risk ratio was 1.61 (95% CI: 1.32–1.97, p < 0.0001) and the risk difference was 0.25 (95% CI: 0.12–0.39, p < 0.0001), all in favour of combined treatment with hyperthermia and radiotherapy over radiotherapy alone. Acute and late grade III/IV toxicities were reported to be similar in both the groups. Conclusions: Hyperthermia along with radiotherapy enhances the likelihood of CR in HNCs by around 25% compared to radiotherapy alone with no significant additional acute and late morbidities. This level I evidence should justify the integration of hyperthermia into the multimodality therapy of HNCs.

Radiotherapy infrastructure and human resources in Europe – Present status and its implications for 2020

Radiotherapy (RT) is required for nearly half of the newly diagnosed cancer patients. To optimise the quality and availability of RT, guidelines have been proposed by European Society for Radiotherapy and Oncology-QUAntification of Radiation Therapy Infrastructure And Staffing Needs (ESTRO-QUARTS) and the International Atomic Energy Agency (IAEA). This study evaluates the present status of RT capacity in Europe and the projected needs by 2020 as per these recommendations. Thirty-nine of the 53 countries, listed in Europe by the UN Statistical Division, whose cancer incidences, teletherapy and human resources were available in the Global Cancer Incidence, Mortality and Prevalence (GLOBOCAN), International Agency for Research on Cancer (IARC) and DIrectory of RAdiotherapy Centres (DIRAC) (IAEA) databases were evaluated. A total of 3550 teletherapy units (TRT), 7017 radiation oncologists (RO), 3685 medical physicists (MP) and 12,788 radiotherapy technologists (RTT) are presently available for the 3.44 million new cancer cases reported annually in these countries. The present infrastructure and human resources in RT are estimated to provide RT access to 74.3% of the patients requiring RT. The current capacity in TRT, RO, MP and RTT when compared with recommended guidelines has a deficit of 25.6%, 18.3%, 22.7% and 10.6%, respectively. Thus, to respond to requirements by 2020, the existing capacity needs to be augmented by an additional 1698 TRTs, 2429 ROs, 1563 MPs and 2956 RTTs. With an imminent rise in cancer incidence, multifaceted strategic planning at national and international levels within a coordinated comprehensive cancer control programme is highly desirable to give adequate access to all patients who require radiotherapy across Europe. Specific steps to address this issue at national and continental levels involving all major stakeholders are proposed.

Implications of contrast-enhanced CT-based and MRI-based target volume delineations in radiotherapy treatment planning for brain tumors.

Delineation of various target volumes using contrast-enhanced magnetic resonance imaging (MRI) and/or computed tomography (CT) constitutes the primary step for radiation therapy planning (RTP) in brain tumors. This study presents a quantification and comparative evaluation of the various clinical target volumes (CTV) and gross target volumes (GTV) as outlined by contrast-enhanced CT and MRI, along with its implications for postoperative radiotherapy of brain tumors. Twenty-one patients of gliomas were considered for this prospective study. Peritumoral edema as CTV and residual tumor as GTV were delineated separately in postoperative contrast-enhanced CT and MRI. These volumes were estimated separately and their congruence studied for contrast-enhanced CT and MRI. Compared to MRI, CT underestimated the volumes, with significant differences seen in the mean CTV (mean +/- SD: -62.92 +/- 93.99 cc; P = 0.006) and GTV (mean +/- SD: -21.08 +/- 36.04 cc; P = 0.014). These differences were found to be significant for high-grade gliomas (CTV: P = 0.045; GTV: P = 0.044), while they were statistically insignificant for low-grade gliomas (CTV: P = 0.080; GTV: P = 0.117). The mean differences in the volumes for CTV and GTV were estimated to be -106.7% and -62.6%, respectively, taking the CT volumes as the baseline. Thus, even though, electron density information from CT is essential for RTP, target delineation during postoperative radiotherapy of brain tumors, especially for high-grade tumors, should be based on MRI so as to avoid inadvertent geographical misses, especially in the regions of peritumoral edema.