A method to increase the rectum separation distance during brachytherapy

Abstract

Present invention discloses a novel method for cervical cancer patients undergoing brachytherapy which combines a rectal retractor (RR) blade with radio-opaque vaginal packing (VP) to displace the rectum and bladder away from radiation sources in High-dose-rate (HDR) intracavity brachytherapy (ICB). While doing conventional brachytherapy with T&R applicators, the inventors deliberately placed radio-opaque vaginal packing (VP), posterior and cranial to the rectal retractor (RR) blade, to retract the rectum away from the radiation sources. The combination procedure Rectal retractor (RR) and Radio-opaque vaginal opaque (VP) is less time consuming and leads to significant reduction in dose to ICRU rectal points to 13.03% and reduction in rectal dose per fraction is 15% (p = 0.013).

Description

[0001] A METHOD TO INCREASE THE RECTUM SEPARATION DISTANCE

[0002] DURING BRACHYTHERAPY

[0003] FIELD OF INVENTION

[0004] The present invention relates to the field of Medical Radiology and methods to save healthy organs during radiotherapy. More particularly it relates to a method to increase the rectum separation distance from the applicator which houses the radioactive sources during brachytherapy in Cervical Cancer patients.

[0005] BACKGROUND OF THE INVENTION

[0006] Cervical cancer- Cervical cancer is a type of cancer that occurs in the cells of the cervix (lower part of the uterus). Cervical cancer is one of the leading cause of death among the females worldwide. However, cervical cancer can be cured with surgery and definitive radiotherapy with or without chemotherapy, (https: / / www.cancer.gov / types / cervical)

[0007] Radiation therapy for cancer treatment- Radiation therapy is also known as radiotherapy and is widely used for the treatment of various types of cancers including cervical cancers. Radiotherapy uses high doses of radiation to kill cancer cells and shrink tumors, at high doses, radiations kills the cells or limits their growth by destructing their DNA. Widely there are two types of radiation therapies including external beam radiation therapy (EBRT) and Internal radiation therapy (IRT) and these two techniques can also be used in combination, (https: / / www.cancer.gov / about- cancer / treatment / types / radiation-therapy)

[0008] Brachytherapy is a form internal radiation therapy for treatment of cancer, in which a source of radiation is placed inside the patient’s body near the cancers for effective management of same. The type of brachytherapy, which is used to treat cervical cancer is known as Intracavitary brachytherapy (ICB). In Intracavitary brachytherapy (ICB), a radiation source is placed inside the vagina, very close to the cervix. It is mainly used in addition to External Beam Radiation Therapy (EBRT) as a part of the main cervical cancer treatment. Careful placement of radioactive material (source) is very crucial as it allows localized and precise irradiation of the tumors. a (men t %20for%2 (fcervi ca I %2 Ocancer. )

[0009] Types of Brachytherapy-

[0010] Low Dose Rate (LDR) Brachytherapy- LDR implants usually releases low doses of radiations continuously for 1 to 7 days till then, the patient stays in the hospital with instruments holding the radioactive material in place.

[0011] High Dose Rate (HDR) Brachytherapy- HDR implants releases high doses of radiation for 10-20 minutes. For each high-dose treatment, the radioactive material is inserted for a few minutes and then removed after the treatment process. High-dose-rate (HDR) brachytherapy (BT) is advantageous over LDR brachytherapy, as it include outpatient treatment, minimal radiation exposure to healthcare providers, and avoidance of prolonged patient immobilization.

[0012] Brachytherapy (BT) is an essential component of the definitive management of cervical cancer, as it delivers high dose to the gross disease present in the cervix. Simultaneously, the surrounding normal organs are at high risk to receive radiation dose beyond their tolerance limit. Hence, there is a need for optimal displacement and sparing of nearby organs at risk (OARs) such as bladder and rectum from the high dose region around the applicators (radiation sources) in order to decrease the risk of toxicities. During the transition from LDR (low-dose-rate) to HDR (High-dose-rate), it was desirable to further reduce the percentage of the prescribed dose that reached organs at risk (OARs) by increasing the distance between the OARs and applicators. Hence, various packing techniques for sparing of organs at risks along with applicators (source of radiation) are used during brachytherapy.

[0013] Packing technique- vaginal packing is used to fix the applicator and displace organs at risk (OAR) during High Dose Rate (HDR) intracavitary brachytherapy (ICB). Radiation dose escalation to the tumor increases overall response and survival but it may increase collateral dose to the organs at risk (OARs) including bladder and rectum, thus leading to corresponding dose-dependent late toxicities. Hence, in order to achieve dose reduction, the rectum and bladder must be displaced away from the applicators using vaginal packing technique. Further, optimal packing technique in brachytherapy is crucial as it stabilizes the applicator and aids in displacement of bladder and rectum away from the source without displacing the cervix. Some methods for displacing OAR include vaginal gauze packing, use of commercially available retractor blades, vaginal balloons including pairs of deflated balloons and retractor crafted in house.

[0014] Types of applicators along with packing technique used for Brachytherapy -

[0015] Tandem and ovoid (T&O) applicators, in which the radioactive material can be placed in a small metal tube (called a tandem) that goes in the uterus, along with small round metal holders (ovoids) placed near the cervix, Tandem and ring (T&R) applicators, in which a small metal tube (called a tandem) that goes in the uterus and round holder (like a disc) is placed close to the cervix and Tandem and vaginal cylinder applicators are most commonly used applicators.

[0016] In various brachytherapy sessions, Tandem and Ovoid (T&O) applicators along with radio-opaque vaginal packing (VP) and Tandem and ring (T&R) applicators along with rectal retractor (RR) blades are two most commonly used applicators for intracavitary brachytherapy (ICB) in cervical cancer. However, with introduction of high-dose-rate (HDR) brachytherapy (BT) use of tandem and ring (T&R) applicator with rectal retractor (RR) blades has been initiated. Timely, T&R applicators become popular in image guided BT due to their reproducible geometry and ease of application compared to T&O applicators. However, in dosimetric comparisons between the two applicators, T&O applicators treat larger volumes then T&R applicators. Further, in terms of rectal doses, T&R applicators with RR (Rectal retractor) blades offer significantly better rectum sparing than T&O applicators with VP (radio-opaque vaginal packing).

[0017] However, none of the studies discloses the combination of radio-opaque vaginal packing (VP) along with rectal retractor (RR) for rectum sparing during brachytherapy procedures performed using tandem and ring (T&R) applicators in cervical cancer. However some of the existing packing techniques with T&O applicators are as below-

[0018] Existing packing techniques-

[0019] Similar packing techniques to displace OARs with T&O applicators are as below -

[0020] Commercially available vaginal balloon packing system- It provides OAR protection in HDR-BT performed using T&O applicators. However, due to the major benefit of reproducibility among fractions and minimum reliance on technique, balloon packing was suggested for low-volume centers with little experience in gauze packing. Bladder and rectum doses using a standard size, bladder-rectum spacer balloon (BRSB) with standard gauze packing. The BRSB resulted in significant reductions in both the dose and interfraction dose variation for D2cc of the rectum, but no significant reduction in dose variation to other sub-volumes of the bladder and rectum was seen. The use of a BRSB was recommended when there is limited physician expertise or if general anesthesia is not routinely used. In patients with a narrow vagina, a non-transparent balloon obscured the visualization of the external os and crowded inside the vagina due to oversizing, which made the applications difficult and time consuming.

[0021] Speculum-based VP (SBVP) with conventional gauze packing during tandem and ovoid HDR-ICB. In patients with appropriate anatomy, improved bladder sparing and comparable rectum sparing, relative to that achieved with gauze packing, could be achieved. However, in patients requiring dose optimization, SBVP did not differ from conventional gauze for bladder sparing and was associated with significant increases in rectal dose volume parameters. Further, it was found that the insertion of the second ovoid through the speculum to be challenging in the narrow vaginal canals.

[0022] Intravaginal FBs in addition to conventional packing, results in a significant dose reduction to the bladder and rectum due to further displacement of these structures. However, it was insisted that proper vaginal packing (VP) is crucial and that the addition of FBs to properly placed conventional packing helped to reduce the doses to the rectum and bladder. One challenge is that vaginal balloons are tedious to craft in-house, thus increasing the time costs for medical professionals, and the customized packing of this method imparts a degree of operator dependence.

[0023] However, there are no existing patents, studies or non-patent literatures that discloses combination of rectal retractor (RR) blades with radio-opaque vaginal packing to displace the rectum away from the radiation sources, which can significantly reduce the ICRU rectal point doses. Further, the packing techniques used in place of conventional radio-opaque vaginal packing (VP) to displace Organs at risks (OARs) with Tandem and ovoid (T&O) applicators as discussed above are tedious, time consuming, in-insignificant in dose reduction. Hence, there was a need to disclose such as packing technique which is not tedious, less time consuming and significantly reduces the ICRU rectal point doses. INNOVATIVE SOLUTION PROPOSED BY THE INVENTORS

[0024] There are no existing packing techniques in brachytherapy, which combines a rectal retractor (RR) blade with radio-opaque vaginal packing (VP) to displace the rectum away from radiation sources in High-dose-rate (HDR) intracavity brachytherapy (ICB) using tandem and ring (T&R) applicators. Further, the existing techniques for rectum sparing using T&O applicators as discussed above are tedious, time consuming, in-significant in dose reduction. Hence, in order to overcome these drawbacks, inventors of present invention, logically modified the conventional brachytherapy method for using T&R applicators by deliberately placing radio-opaque vaginal packing (VP), posterior and cranial to the rectal retractor (RR) blade, to further retract the rectum away from the radiation sources. Further, the combination procedure Rectal retractor (RR) and Radioopaque vaginal opaque (VP) is less time consuming, hence overcomes the drawbacks associated with existing vaginal packing technique. The combination of RR (Rectal retractor) blade and radioopaque vaginal packing (VP) leads to significant reduction in dose to ICRU rectal points compared to RR blade alone in HDR (High-dose-rate) ICB (Intracavitary brachytherapy) for cervical cancer performed using T&R applicators.

[0025] The novel packing technique for brachytherapy as disclosed in present invention is not anticipated by any of the prior art patents or non-patents literature, however some of the patents and journals related to present invention are as below -

[0026] PRIOR ART PATENTS

[0027] Patent Application No: US20150190621A1 “Device and Method for Tissue Displacement in Brachytherapy”

[0028] The above patent discloses a device and method for displacing healthy or normal tissue away from radiation exposure during brachytherapy comprises a tandem in the centre, a ring and an inflatable component (e.g. a balloon) that is attached to the ring of a tandem. The above cited patent comprises a tandem in the centre, a ring and an inflatable component (e.g. a balloon) that is attached to the ring of a tandem. Whereas the combination of rectal retractor blade along with radio-opaque vaginal packing for rectum sparing is not disclosed in above cited patent.

[0029] Patent Application No: US20080064916A1 “Split-ring brachytherapy device and method for cervical brachytherapy treatment using a split-ring brachytherapy device”

[0030] The above invention discloses a split-ring brachytherapy device for cervical brachytherapy treatment comprises of a central tandem, an adjustable split ring tubes that are adjustable in relation to a cervical axis and an adjustable rectal retractor which is attached to the split ring to reduce the radiation dose to a rectal wall by increasing the distance them. However the combination of rectal retractor (RR) blade and radio-opaque vaginal packing (VP) for rectum sparing is not disclosed in cited patent.

[0031] Patent Application No: US9345907B2 “Bladder and / or rectum extender with exchangeable and / or slideable tungsten shield”

[0032] The above cited patent discloses a device to protect a rectum from radiation during brachytherapy comprises of tandem, a ring and rectum retractor. Further the rectum retractor disclosed in above cited patent is slide-able, an exchangeable and moveable shield, made of tungsten which will protect the rectum by sliding as required in order for treatment of cervix cancer. However the combination of rectal retractor (RR) blade and radio-opaque vaginal packing (VP) for rectum sparing is not disclosed in cited patent.

[0033] Non-Patent Literature

[0034] Kyu Chan Lee, Tae-Hyun Kim, Jin-Ho Choi and Myung-Sun Choi “Use of the Rectal Retractor to Reduce the Rectal Dose in High Dose Rate Intracavitary Brachytherapy for a Carcinoma of the Uterine Cervix” February 2004Yonsei Medical Journal 45(l):113-22

[0035] The above cited publication discloses a rectal retractor device to reduce the rectal dose in high dose rate intracavitary brachytherapy comprises of tandem & ovoid and rectal retractor blade which further filled with barium and anteroposterior and lateral radiographs were then taken with and without the rectal retractor. The experimental study showed that the rectal retractor filled with barium is more effective for reducing the rectal dose during Brachytherapy. However the combination of rectal retractor (RR) blade and radio-opaque vaginal packing VP) for rectum sparing is not disclosed in cited patent.

[0036] “High-Dose Rate (HDR) Brachytherapy Implant for the Cervix or Endometrium (Ring and Tandem or Ring and Tandem with Needles)” Hillman Cancer Center.

[0037] (https: / / hilhnan.upmc.com / patients / community-support / education / radiation-therapy / hdr- brachytherapy-implant-cervix-ring-tandem)

[0038] The above cited publication discloses a high dose rate brachytherapy implant for the cervix comprises of ring and tandem with needles and a fixed spatula-like instrument, called a rectal retractor which is attached to the T&R and is helping in limiting the dose of radiation to the rectum. However the combination of rectal retractor (RR) blade and radio-opaque vaginal packing (VP) using T &R applicator for rectum sparing is not disclosed in cited patent.

[0039] OBJECT OF THE PRESENT INVENTION

[0040] The primary object of the present invention is to disclose a method to increase the rectum separation distance during brachytherapy in Cervical Cancer patients.

[0041] Another object of the present invention is to disclose a method to decrease the dose to ICRU rectal point in HDR ICB brachytherapy.

[0042] SUMMARY OF THE INVENTION

[0043] Present invention discloses a method to increase the rectum separation distance during brachytherapy in Cervical Cancer patients, which combines rectal retractor (RR) blade with radio-opaque vaginal packing (VP) to displace the rectum away from radiation sources in High-dose-rate (HDR) intracavitary brachytherapy (ICB) using tandem and ring (T&R) applicators. The inventors of present invention, modified the conventional Brachytherapy procedure for using T&R applicators by deliberately placing radio-opaque vaginal packing (VP), posterior and cranial to the rectal retractor (RR) blade, to further retract the rectum away from the radiation sources. The combination procedure of combining rectal retractor (RR) and radio-opaque vaginal opaque (VP) is less time consuming and leads to significant reduction in dose to ICRU rectal points compared to RR blade alone in HDR (High-dose-rate) ICB (Intracavitary brachytherapy) for cervical cancer performed using T&R applicators. Further, when T&R applicators are used with modified approach of combining radio-opaque vaginal packing with a fixed RR blade, then average reduction in the mean dose to the ICRU rectal point (expressed as % of point A dose) was 13.03% per fraction as compared to the conventional approach of using RR alone (p = 0.001). In the subset analysis, this average reduction in rectal dose per fraction was 15% (p = 0.013)

[0044] DESCRIPTION OF DRAWINGS

[0045] Figure 1- Planning images of one patient who completed 50Gy EBRT, followed by three fractions of 7Gy HDR BT using the same tandem ring applicator with a tandem length of 6 cm, angle of 45° and a ring size of 3 cm during two consecutive fractions.

[0046] (A) Applicator placement during the first fraction using a RR alone for rectal separation. Pl = ICRU bladder point, P4 = ICRU rectal point.

[0047] (B) Same applicator placement during the second fraction using a combination of rectal retractor and radio-opaque vaginal packing (RR + VP). Pl = ICRU bladder point, P4 = ICRU rectal point.

[0048] (C) First fraction delivered with RR alone,

[0049] (D) The second fraction delivered using the same applicator parameters but a combination of RR + VP for rectal separation.

[0050] Figure 2- Nucletron tandem-ring(TR) applicator and a rectal retractor(RR) with a tandem length of 6cm, angle of 45° and a ring size of 3cm.

[0051] Figure 3- Stainless steel round surgical bowls. A) Half filled with normal saline. B) Half filled with ixohexol contrast solution with normal saline in ratio of 1:1. C) A roll of vaginal packing (prepared from a custom gauze bandage roll of width 2 inches (15cm). lateral edges are folded over thrice so that effective width of VP roll is 1.5- 2.0 cm.

[0052] DETAILED DESCRIPTION OF THE INVENTION

[0053] The following description is the best-contemplated mode of carrying out the invention.

[0054] The description is made for the purpose of illustrating the general principles of the invention and should not be taken in a limiting sense. Present invention discloses a novel packing technique by combining radio-opaque vaginal packing (VP) with rectal retractor (RR) blade for rectum sparing during brachytherapy in cervical cancer. Inventors of present invention, logically modified the conventional Brachytherapy procedure for using tandem and ring (T&R) applicators by deliberately placing radio-opaque vaginal packing (VP), posterior and cranial to the rectal retractor (RR) blade, to further retract the rectum away from radiation sources. Vaginal packing (VP) is achieved with a thin ribbon, and the extent and amount of packing can be customized for a range of spaces and to different patients. Gradually, in all BT procedures, in which the patient’s anatomy allowed for the placement of T&R applicators with RR blades, combination of radio-opaque VP with an RR blade was used.

[0055] Rectal retractor (RR) blade is of standard size for all patients, whereas the capacity of vaginal fornices varies from patient to patient. There are patients with roomy vagina / fornices and at the other end there are patients with obliterated / absent vaginal fornices or narrow vagina. The remaining space in the fornices, after placement of the RR blade, especially in the case of roomy vagina, becomes inaccessible for packing after the RR blade is assembled. For this reason, in conventional procedures performed using T&R applicators with RR blades, vaginal gauze packing is possible only in the anterior and center, but not posteriorly, as the posterior space is occupied by the RR blade. Inventors deliberately place radio-opaque VP based on the available space in the fornices, without overstretching to avoid mucosal tears. The goal is to increase rectum separation and hence, a greater reduction in rectal dose. The same can be achieved by using traditional vaginal packing instead of a rectal retractor blade since there will be no obstruction due to the presence of the RR blade, and the amount of packing can be customized as per the patient’s anatomy.

[0056] Step by step method to increase the rectum separation and decrease in rectal dose to ICRU rectal point in HDR ICB for cervical cancer after inserting T & R applicator is disclosed below by way of example:

[0057] Example 1:

[0058] All sessions were carried out in accordance with the classical ICB procedure for performing intracavitary brachytherapy (ICB) under intravenous sedation and analgesia in our department. A ring applicator (Fig-2) of the largest diameter that could be accommodated in the upper vagina was selected and threaded over the central tandem. The ring was then positioned to encircle the cervix and clamped to interlock with central tandem. Before assembling the rectal retractor (RR) blade, the following additional steps are taken- The available space posterior and superior to the ring cap in the upper vagina was then assessed to determine whether placement of rectal retractor blade and additional vaginal packing would be possible. To enable additional rectal retraction, radio-opaque gauze packing was carefully placed in layers, posterior to the ring cap. The radio-opaque vaginal packing is thin ribbon-shaped cotton gauze in a shape of a roll of variable length, measuring approximately 1.6 to 2cms in width FFig-31. During the procedure, it is soaked in ixohexol contrast diluted with normal saline in a ratio of 1:1. It is crucial to ensure that the space behind the ring cap, in the fomices and upper vagina, is optimally filled with packing without any obstruction and undue resistance or pressure to the placement and assembly of the rectal retractor. If necessary, some of the layers of gauze packing could be pulled back to allow for more space for accommodating rectal retractor blade, which is a crucial decision to avoid mucosal tear. Whole assembly is now kept softly pushed against the cervix to evaluate the remaining space between rectal retractor and lower vagina. If any scope for additional packing was identified, then further packing in the lower vagina, was carried out with the help of long forceps, taking an approach from posterior aspect of the rectal retractor blade.

[0059] The above described steps for placement of vaginal packing are not taken during conventional procedures when RR alone is used for rectum separation. Packing in the center to stabilize the applicator assembly and in the anterior to displace bladder is then accomplished in all procedures. This modified procedure of ICB allows for customized vaginal packing and helps to supplement the displacement achieved with conventional use of RR alone. The additional steps described for customization of VP for different patients and vaginal spaces highlights the importance of physician skill and judgement in achieving optimal treatment outcomes, and is not time consuming.

[0060] So to summarize, the steps are as below:

[0061] 1. Taking radio opaque Vaginal packing(VP) in the form of thin foldable ribbon made up of cotton gauze. The amount of radio opaque VP varies as per the available vaginal space.

[0062] 2. Packing the Radio Opaque Vaginal packing(VP) in the vaginal fornices and along the upper part of the posterior wall, followed by assembly of RR blade, to increase the rectum separation and reduce rectal dose by 13%. 3. Standard gauze packing soaked in ixohexol contrast diluted with normal saline in a ratio of 1 : 1 is used to stabilize the applicator and to push the bladder anteriorly.

[0063] Pre- Clinical Trials and implementation:

[0064] The applicants and inventors being doctors themselves applied this method during brachytherapy procedures on various patients. The details are as below:

[0065] Patients who have completed EBRT and had an adequate tumor response to receive brachytherapy are reviewed. A cohort of 24 patients who received at least one fraction via Tandem and ring (T&R) applicators are selected and the treatment plans with standard loading patterns and reference points prescribed as per the ICRU-38 report were considered eligible for analysis. Patients treated with plans that deviated from the ICRU-38 guidelines, with suboptimal placement of the applicators due to a learning curve or with suboptimal dose prescriptions were considered not eligible for analysis.

[0066] Normal Brachytherapy procedure and planning is as below-

[0067] The brachytherapy is carried out under intravenous sedation and analgesia in all the patients.

[0068] Both T&O and T&R applicators were used according to physician preference and logistic accessibility to the applicator sets.

[0069] After inserting the central tandem, the largest diameter ring that the upper vagina could accommodate was chosen and threaded over the tandem.

[0070] The T&R applicator was positioned to encircle the cervix and was pushed against the cervix. While the ring was kept in position, the available space posterior and superior to the ring in the upper vagina was visualized to assess its capacity for accommodating a rectal retractor and additional vaginal packing.

[0071] The RR was placed and clamped with an interlock system.

[0072] Additional Novel steps: the Radio Opaque Vaginal packing (VP) is soaked in ixohexol contrast diluted with normal saline in a ratio of 1 : 1.

[0073] Posterior to the ring cap, radio-opaque VP in layers, was deliberately placed in the vaginal fornices and along the upper part of the posterior vaginal wall, as per the available capacity, before the placement and assembly of RR blade, without overstretching the mucosa to avoid mucosal tears. Radio-opaque vaginal packing (VP) was also used to stabilize the applicator and to push the bladder anteriorly in all sessions. the radio opaque VP is in the form of thin ribbon-shaped cotton gauze in a shape of a roll of variable length, measuring 1.5 cm to 2 cm in width. the amount of radio opaque VP varies as per the available vaginal space.

[0074] The above steps increase the rectum separation and decrease the radiation dose to ICRU rectal point in HDR ICB for cervical cancer, by 13%.

[0075] RESULTS AND DISCUSSION:

[0076] After the procedure, orthogonal radiographs were taken by a conventional simulator and the images were transferred to the treatment planning system via a digital imaging and communication in medicine (DICOM) connection.

[0077] Intracavity Brachytherapy (ICB) treatment planning was performed on- Oncentra Brachy v4.6 and was delivered by Nucletron, MicroSelectron HDR V3 (18 channel) remote after loading machine using lr-192.

[0078] The orthogonal images taken with the applicators in place were reconstructed, and source positions were loaded according to standard loading pattern following the Manchester system.

[0079] Point A was taken as 2 cm superior to the lower most intrauterine source along the axis of the intrauterine tandem and 2 cm lateral in the plane of the uterus. A fixed step size of 2.5 mm was used for all applications. The dwell times were equal for all dwell positions. Only lateral dwell positions in the ring were activated. The doses to the ICRU rectal point, bladder point and point B were taken according to the recommendations of the ICRU-38 and reported per insertion in all cases.

[0080] Dosimetric calculations-

[0081] For dosimetric calculations, Tandem length, tandem angle, and ring size of the applicator used during Intracavity Brachytherapy (ICB) were the parameters, which were considered. The dwell positions along the central tandem and in the ring were noted for each individual fraction. The accuracy of the prescribed point A, point B, rectal point and bladder points was verified. The absolute dose prescribed to point A is different in the three regimens, hence it is normalized to 100% to simplify the data analysis. For the same reason, the absolute doses to point B and the ICRU rectal and bladder points were also expressed as a percentage of the prescription dose.

[0082] Further, the inventors measured a pear-shaped 100% isodose reference volume (Volref) for each ICB session and described the volume in terms of its three maximal dimensions:

[0083] Height (dh ) measured in an oblique frontal plane along the intrauterine sources;

[0084] Width (dw) measured in the same plane perpendicular to the intrauterine sources; and

[0085] Thickness (dt ) measured in the oblique sagittal plane perpendicular to the intrauterine sources.

[0086] Volref was calculated as the product of dh xdw xdt. Similarly, H, W and T were applied to the same parameters of a 60 Gy reference volume (Vol60Gy), which was defined as the 60 Gy isodose surface resulting from the additional dose contribution from whole pelvic irradiation and all intracavitary insertions. Applying the linear-quadratic model and an alpha / beta ratio of 10 Gy for the tumour effect, the isodose curve, which encloses the 60 Gy volume for patients who received 50 Gy EBRT followed by two sessions of 9 Gy each, was represented by 3.15 Gy. Similarly, the 60 Gy isodose volume was enclosed by 2.35 Gy in patients who received 50 Gy EBRT followed by three sessions of 7 Gy each. The total reference air kerma (TRAK) values for each fraction were also recorded.

[0087] Statistical analysis

[0088] Mean values and standard deviations for baseline characteristics, stage and applicator parameters were calculated for 21 applications in the conventional (RR) group and 17 in the combination (RR+VP) group. These mean values were then compared between the two groups with independent sample t tests. Paired sample t tests were used for subset analysis. All statistical analyses were performed using IBM Corp. Released 2019. IBM SPSS Statistics for Windows, Version 26.0. Armonk, NY : IBM Corp. A p value < 0.05 was considered significant.

[0089] Results-

[0090] Treatment Groups-

[0091] Total 17 women received two fractions of 9GY each

[0092] Four women received three fractions of 7Gy each

[0093] One women received four fractions of 7Gy each and Two women received two fractions of 9.5Gy each.

[0094] A total of 45 ICB sessions were delivered using (T&R) applicators out of which, 7 fractions were not eligible for analysis because of following reasons- the prescribed dose was too low in two treatment plans; suboptimal applicator placement in two sessions; and the standard loading patterns and ICRU-38 recommendations were not followed in three sessions.

[0095] Hence, 38 sessions were remaining for analysis, 21 ICB sessions performed using an RR alone constituted the RR group, and 17 ICB sessions, in which an RR blade was combined with radioopaque VP, constituted the RR+VP group.

[0096] Patient characteristics -

[0097] Both groups were statistically balanced with regard to the distribution of variables, such as stage and applicator characteristics, which can influence dose-volume parameters. The same are disclosed in Table 1 below-

[0098]

[0099] RR- Rectal retractor group; RR+VP- Rectal retractor along with radio-opaque vaginal packing group

[0100] Table 1- distribution of stage and applicator-related characteristics in the two groups Dosimetric parameters

[0101] The comparison between dose and volume parameters is shown in Table 2.

[0102] For the same dose prescribed to point A in both groups, the mean dose to the ICRU rectal point was 39.7% of the prescription dose (range, 28.8%-50.3%; median 38.6%) in the RR+VP group and 52.7% (range, 46.9%-63.6%; median 51.6%) in the RR group. There was a 13% reduction in the mean dose to the ICRU rectal point (p = 0.001).

[0103] The mean dose to the ICRU bladder point was 55.4% of the prescription dose (range, 26.3%-73.6%; median 57.4%) in the RR+VP group and 45.3% (range, 23.6%-72.7%; median 46.9%) in the RR group. There was a 10.1% increase in the mean dose to the ICRU bladder point (p = 0.024).

[0104] The mean dose to point B was similar at 22.7% of the prescription dose (range, 20.4%-24.1%; median 22.8%) in the RR+VP group and 22.8% (range, 20.1%-25.2%; median 23.0%) in the RR group.

[0105] The mean reference volume (Volref) for the BT part of treatment expressed as dh x dw xdt was similar at 142.2 cc (range, 107.6-195.7 cc; median 146.0 cc) in the RR+VP group and 143.7 cc (range, 103.4-197.8 cc; median 149.9 cc) in the RR group.

[0106] The mean 60 Gy reference volume (Vol60Gy) expressed as HxWxT was similar at 557.2 cc (range, 326.3-703.0 cc; median 582.3 cc) in RR+VP group and 582.99 cc (range, 327.6 cc-721.0 cc; median 616.3 cc) in the RR group.

[0107] The mean TRAK value (Gy / hour at 1 m) per application was also similar at 0.00446 (range, 0.00339-0.00566; median 0.00455) in the RR+VP group and 0.00476 (range, 0.00349-0.00561; median 0.00498) in the RR group.

[0108]

[0109] RR, Rectal retractor group; RR+VP, Rectal retractor along with radio-opaque vaginal packing group; ICRU, International Commission on Radiation Units & Measurements; CI, Confidence interval; SD, Standard deviationaStatistically significant p values are shown in bold italic print

[0110] Table 2- Comparison of dose and volume parameters between the two groups

[0111] Subset analysis-

[0112] Patients differed between the two comparison groups. The individual anatomical variations among patients may be a possible confounding factor. However, when two methods, i.e., the combination of RR+VP and RR alone, were applied to the same patient during different insertions, patients could act as their own internal control, thus eliminating this possible confounding effect. In an attempt to account for this, subset analysis of ICB fractions was performed on five such women who received at least one fraction with each method. In these women, the ICB sessions that were done using the same tandem length, angle and ring size during both the combination procedure (RR+VP) and the conventional procedure (RR alone) were compared. This subset analysis was performed as an intrapatient comparison, and the results are presented in Table 3.

[0113] For the same dose prescribed to point A in both groups, the mean dose to the ICRU rectal point was 40.5% of the prescription dose in the RR+VP group and 55.5% in the RR group. There was a 15.0% reduction in the mean dose to the ICRU rectal point (p = 0.013).

[0114] The mean dose to the ICRU bladder point was 59.9% of the prescription dose in the RR+VP group and 46.5% in the RR group. There was a 13.4% increase in the mean dose to the ICRU bladder point (p = 0.019).

[0115] The mean point B doses, mean reference volumes (Vref) for the BT part of treatment, mean 60 Gy reference volumes (V60Gy) and mean total TRAK values were similar in both groups. Figure 1 shows simulation and planning images of the fractions received by the same patient with the two methods of rectum separation. As per Figure 1 (C) during the first fraction delivered with RR alone, a pear-shaped reference volume (Vref) enclosed within a 7 Gy (100%) red isodose curve was 149.10 cc (dh x dw x dt ) and that a 60 Gy reference volume (V60Gy) represented by a 2.4 Gy (33.6% of 7 Gy) green isodose curve in this case was 643.1 cc (H x W x T) (see text details on measuring the dimensions and calculating the 60 Gy volume). The point B dose was 1.6 Gy (22.7% of point A dose), ICRU rectal point dose was 4.17 Gy (59.6% of point A), ICRU bladder point dose was 2.5 Gy (35.3% of point A) and TRAK value was 0.00392 Gy. Further, as per figure 1(D), During the second fraction delivered using the same applicator parameters but a combination of RR + VP for rectal separation, the reference volume (Vref) enclosed within a 7 Gy (100%) red isodose curve was 156.6 cc (dh x dw x dt ), and the 60 Gy reference volume (V60Gy) enclosed by a 2.4 Gy green isodose curve was 682.4 cc (H x W x T). The point B dose was 1.6 Gy (23.8% of point A dose), the ICRU rectal point dose was 2.7 Gy (38.2% of point A), the ICRU bladder point dose was 3.7 Gy (52.9% of point A) and the TRAK value was 0.00406 Gy. In this patient, the BT fraction delivering the same prescribed dose to point A and treating equal 60 Gy isodose volumes, using a rectal retractor in combination with radio-opaque vaginal packing (RR+VP) reduced the dose to the ICRU rectal point by 1.5 Gy (21.4%) compared to the fraction delivered using a RR alone.

[0116] RR, Rectal retractor group; RR+VP, Rectal retractor along with radio-opaque vaginal packing group; ICRU, International Commission on Radiation Units & Measurements; NA, Not applicable a Statistically significant p values are shown in bold italic print; p value of 0.05 is significant

[0117] Table 3. Comparison of rectal retractor alone (RR) versus the combination of rectal retractor with vaginal packing (RR+VP) in a subset of patients who received HDR fractions with both methods of rectum separation for different insertions.

[0118] Hence, it is concluded that when T&R applicators are used with modified approach of combining radio-opaque vaginal packing with a fixed RR blade, then the average reduction in the mean dose to the ICRU rectal point (expressed as % of point A dose) was 13.03% per fraction as compared to the conventional approach of using RR alone (p = 0.001). In the subset analysis, this average reduction in rectal dose per fraction was 15% (p = 0.013) The present invention is novel as same is not anticipated by any of the prior art patents and non- patents literature.

[0119] The technological advancement lies disclosure a novel method to increase the rectum separation distance during brachytherapy in Cervical Cancer patients. The dose reaching the healthy organs is reduced by 13% which is much significant reduction. The same is achieved by combining a rectal retractor (RR) blade with radio-opaque vaginal packing (VP) to displace the rectum and bladder away from radiation sources in High-dose-rate (HDR) intracavity brachytherapy (ICB). In present invention, inventors deliberately placed radio-opaque vaginal packing (VP), posterior and cranial to the rectal retractor (RR) blade, to retract the rectum away from the radiation sources, which significantly reduces ICRU rectal point doses.

[0120] The present invention does not fall under method for surgical or medical treatment as the method steps are directed towards increasing the rectum separation resulting in decrease of 13 % in rectal dose to ICRU rectal point in HDR ICB for cervical cancer after inserting T & R applicator and RR blade. The radio opaque VP is in the form of thin foldable ribbon made up of cotton gauze. The amount of radio opaque VP varies as per the available vaginal space.

[0121] The manner in which the insertion of T & R applicator and RR blade is carried out is NOT the subject matter of the present invention which would have been categorized as method of treatment or therapeutic method.

[0122] Instead the present invention is a method to push the rectum away from the brachytherapy localized site so that lesser radiation reaches this healthy organ. No special cuts or surgical procedures are carried out for this method because a brachytherapy patient is already under radiation procedure and has RR Blade already inserted in him. This step is not being claimed by the present inventors as it is not new and is a common procedure only.

[0123] Rather when the brachytherapy is already ON, this method step is to be applied. This step claimed in the present invention is optional and additional to the already ongoing Brachytherapy process. So the present invention being a method to increase the rectum separation and decrease the radiation dose to rectum does not fall under the category of a process for medicinal, surgical, curative, prophylactic, diagnostic, therapeutic or treatment to render the human beings or animals FREE OF DISEASE or to increase their economic value.

[0124] The technological advancement over this normal brachytherapy procedure is that by inserting radio-opaque vaginal packing (VP), posterior and cranial to the rectal retractor (RR) blade, the inventors have seen remarkable results in increasing the distance of rectum separation and thereby reduction in ICRU rectal point doses. This was not possible with existing brachytherapy procedures. Considerable intellectual effort has been put in by the inventors as they analyzed the appropriate distance by which the rectal separation should be done and can be done so as to save the healthy organ. Further what material can be inserted which is safe for the patient. How much of the material can be inserted as per available space in vagina, all these questions had to be carefully considered before deciding the final steps of execution. Further a lot of data is analyzed after implementing the technique over the patients. Remarkable reduction in dose at ICRU rectal point was seen which in other words, is a huge technical advancement.

[0125] The industrial application is obvious as the same will improve the life of cancer patient by saving her healthy organs at risk from high-dose-radioactive doses during brachytherapy procedure in cervical cancer treatment with curative intent. A lot of patients have post radiotherapy complications and suffer more due to those. Once the method is implemented by radiotherapists, quality of life of cancer patients will drastically improve.

Claims

WE CLAIM:

1. A method to increase the rectum separation and decrease the radiation dose to ICRU rectal point in HDR ICB for cervical cancer, performed using T & R applicator and RR blade wherein the same consists of packing the Radio Opaque Vaginal packing (VP) posterior to the ring cap before the assembly of the standard rectal retractor (RR) blade, resulting in reduction in rectal dose to ICRU rectal point in HDR ICB by 13%.

2. The method as claimed in claim 1 wherein the Radio Opaque Vaginal packing (VP) is placed in in the Vaginal fornices and along the upper part of the posterior wall.

3. The method as claimed in claim 1 wherein the Radio Opaque Vaginal packing (VP) is placed in layers.

4. The method as claimed in claim 1 wherein the Radio Opaque Vaginal packing (VP) is soaked in ixohexol contrast diluted with normal saline in a ratio of 1 : 1.

5. The method as claimed in claim 1 wherein the radio opaque VP is in the form of thin ribbonshaped cotton gauze in a shape of a roll of variable length, measuring 1.6 cm to 2 cm in width.

6. The method as claimed in claim 1 wherein the amount of radio opaque VP varies as per the available vaginal space.

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